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Wu W, Pei Y, Wang J, Liang Q, Chen W. Association of dietary quality indicators with gallstones in the US: NHANES 2017-2020. BMC Public Health 2025; 25:976. [PMID: 40075394 PMCID: PMC11905512 DOI: 10.1186/s12889-025-21783-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 02/05/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND While dietary factors are known to influence gallstone development, the specific relationships between comprehensive dietary quality indicators and gallstone risk remain poorly understood. This study aimed to explore the association between dietary quality indicators and gallstones using data from the 2017 to 2020 US National Health and Nutrition Examination Survey (NHANES). METHODS A total of 6,623 US adults were extracted from the 2017-2020 NHANES, of which 734 participants self-reported having gallstones. Dietary quality indicators were assessed using 24-hour dietary recall data. We used multivariate logistic regression analysis to evaluate the association between dietary quality indicators and the likelihood of gallstones. To delineate the non-linear relationships and threshold effects, we utilized a restricted cubic spline (RCS) regression model. Subgroup analyses were also performed. RESULTS After adjusting for sex, age, race, education, poverty-to-income ratio, body mass index, large weight loss, alcohol use, smoking, physical activity, diabetes, hypertension, heart failure, coronary heart disease, angina pectoris, heart attack, total calories, total cholesterol, estrogen use, antihyperglycemic drug use, statin use, and glucocorticosteroid use (Model 4), a higher Dietary Inflammatory Index (DII) and lower Alternative Healthy Eating Index (AHEI), Healthy Eating Index (HEI-2020), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean Diet (MED) were all significantly associated with gallstones. Further RCS analysis revealed a nonlinear relationship between the DII and gallstones, with a threshold value of 1.842. Above this threshold, for each unit increase in the DII score, the odds of developing gallstones increased by 27.5%. Subgroup analysis demonstrated that this association was consistent across all subgroups. CONCLUSION Participants with gallstones exhibited poor dietary habits. Adopting a diet that reduces inflammation and supports overall health may help lower the risk of gallstone development, with potential implications for dietary recommendations in clinical practice.
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Affiliation(s)
- Weigen Wu
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Yuchen Pei
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Junlong Wang
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Qizhi Liang
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Wei Chen
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China.
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, P.R. China.
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Peng S, Wei Y, Huang H, Lan C, Zeng Z, Zhu G, Peng T. The mediating role of circulating inflammatory cytokines in causal associations between plasma metabolites and asymptomatic bile duct and cholecyst calculus: A Mendelian randomization study. Medicine (Baltimore) 2025; 104:e41745. [PMID: 40068083 PMCID: PMC11902928 DOI: 10.1097/md.0000000000041745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 12/14/2024] [Accepted: 02/14/2025] [Indexed: 03/14/2025] Open
Abstract
Asymptomatic gallbladder and biliary tract calculus may make into symptomatic disease or bring anxiety for patients. The formation of gallstones was associated with genetic risk factors and metabolic abnormalities. Genome-wide association studies (GWAS) data of 1400 plasma metabolites (PMs) and 91 circulating inflammatory cytokines (CICs) were obtained from the GWAS catalog, while the GWAS data of calculus of gallbladder without cholecystitis and calculus of bile duct without cholangitis or cholecystitis were retrieved from the IEU OpenGWAS project. The causalities from PMs or CICs to asymptomatic bile duct or cholecyst calculus were explored by 2-sample Mendelian randomization (MR) analysis. Furthermore, the MR analyses were implemented from the identified PMs to CICs. Following the false discovery rate adjustment, the significant causalities, including 6 CICs and 5 PMs on asymptomatic biliary stone and 5 CICs and 48 PMs on asymptomatic gallstone, were identified. Fibroblast growth factor 19 (FGF-19) and aspartate/mannose ratio were the common protective factors of asymptomatic biliary tract calculus, while Monocyte chemoattractant protein 2 (CCL-2) may serve as a disease-promoting agent. Moreover, Bilirubin degradation product, C17H18N2O4 (1) levels, and Bilirubin (Z,Z)/etiocholanolone glucuronide ratio were associated with FGF-19 level, while aspartate/mannose ratio was related to TNF-related apoptosis-inducing ligand level. Based on MR analysis, we identified the multiple PMs and CICs, especially FGF-19, which may affect the formation of gallbladder and biliary tract calculus. Moreover, the partial CICs could be the downstream mediator of PMs related to asymptomatic gallbladder and biliary tract calculus. These results contributed to supporting previous studies and provided evidence for disease prevention or management.
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Affiliation(s)
- Shayong Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China
- Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, P.R. China
| | - Yongguang Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China
- Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, P.R. China
| | - Huasheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China
- Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, P.R. China
| | - Chenlu Lan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China
- Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, P.R. China
| | - Zhiming Zeng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China
- Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, P.R. China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China
- Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, P.R. China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China
- Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, P.R. China
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Gu Y, Zhou Z, Zhao X, Ye X, Qin K, Liu J, Zhang X, Ji Y. Inflammatory burden index (IBI) and body roundness index (BRI) in gallstone risk prediction: insights from NHANES 2017-2020. Lipids Health Dis 2025; 24:63. [PMID: 39985035 PMCID: PMC11844043 DOI: 10.1186/s12944-025-02472-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 02/07/2025] [Indexed: 02/23/2025] Open
Abstract
BACKGROUND The Inflammatory Load Index (IBI) and Body Roundness Index (BRI) were employed to evaluate the systemic inflammatory status and body fat. This study aims to elucidate the association between IBI and the prevalence of gallstones, as well as to analyze the mediating role of BRI in this association. METHODS Data from the National Health and Nutrition Examination Survey (NHANES) (2017-2020) were utilized in our cross-sectional study. A total of 2598 participants aged ≥ 20 years were enrolled. The Boruta algorithm, a supervised classification feature selection method, is leveraged to identify the confounding variables most strongly associated with the prevalence of gallstones. Weighted multivariate logistic regression, restricted cubic splines (RCS), and subgroup analyses were employed to investigate the association between IBI and gallstones, assess the presence of a linear association, and evaluate the effect of IBI on gallstone risk across different populations. Finally, the mediating effect of BRI was examined. RESULTS In the fully adjusted model, when IBI was in the highest tertile, each unit increase in IBI (corresponding to an increase of 1 in the natural logarithm of IBI) was linked to a 110.8% higher prevalence of gallstones (OR = 2.108, 95% CI: 1.109-4.005; P = 0.028). The odds ratio for gallstones increased with higher IBI levels across unadjusted, partially adjusted, and fully adjusted models (P for trend < 0.05). This positive association was confirmed to be linear by the RCS curve (P for nonlinear = 0.887). Subgroup analysis indicated that the risk of gallstones was significantly elevated in individuals aged ≥ 60, females, and those with a Poverty-to-Income Ratio (PIR) ≥ 2 (P < 0.05). Mediation analysis revealed that IBI had a significant indirect effect on gallstone prevalence through BRI, with an effect size of 0.0129 (95% CI: 0.0121-0.0136; P < 0.001), and the mediation contributed to 33.24% of the total effect. CONCLUSIONS This study demonstrates a significant linear positive relation of IBI to gallstone prevalence. Furthermore, BRI mediates the effect of IBI on gallstone risk. These findings provide a more precise inflammatory marker for gallstone prevention and treatment. TRIAL REGISTRATION Not applicable.
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Affiliation(s)
- Yuting Gu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Zhanyi Zhou
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xuan Zhao
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xiaolu Ye
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Keyi Qin
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Jiahui Liu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xiao Zhang
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yunxi Ji
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- Department of General Practice, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
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Wang X, Ma M, Zhu L, Qin C, Shao S, Xu X, Gao R, Zhang Z. Exosome-derived miR-107 targeting caveolin-1 promotes gallstone progression by regulating the hepatobiliary cholesterol secretion pathway. Biochem Pharmacol 2025; 232:116735. [PMID: 39725331 DOI: 10.1016/j.bcp.2024.116735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 12/11/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024]
Abstract
Cholesterol gallstone is a disease with high incidence and quality of life. This study aimed to investigate the function of exosome-derived miRNA in gallstone formation and its related molecular mechanism. Exosomes were extracted and isolated from patients with gallbladder stones and age- and gender-matched healthy controls, and exosomal miRNA expression was compared between the two groups. The function of exosomal miR-107 in gallstone formation was evaluated using a lithogenic fed-induced gallstone mouse model. We used a dual luciferase reporter assay to identify the miR-107 target gene. Expression of BSEP and CYP7A1 were detected using Western Blot and immunohistochemical staining to ascertain the role of miR-107 in bile acid transport and cholesterol synthesis. Bile acids, phospholipids, cholesterol and triglycerides were determined with the kit, and cholesterol saturation index was calculated. Liver cholesterol transport-related genes, phospholipid transport-related genes, liver bile salt transport-related genes, sodium-dependent bile acid transporters and organic solute transporters were detected by q-PCR. Exosomal miR-107 high expression was significant in people with gallstones. Inhibitor of miR-107 reduced lithogenic diet-induced gallstone formation in mice. MiR-107 directly inhibited caveolin-1 expression. Inhibition of caveolin-1 reduced the BSEP function. After treatment of miR-107 inhibitor, the expression of BSEP and CYP7A1 was significantly increased compared with gallbladder stones model, but the concentration of bile acid in gallbladder was significantly decreased. miR-107 altered biliary and liver lipid profiles and increased biliary cholesterol saturation index (CSI). Inhibited miR-107 promoted liver homeostasis-related cholesterol and the expression of bile acid transporters. This study revealed that exosome-derived miR-107 promoted gallstone progression by regulating the hepatobiliary cholesterol secretion pathway through targeting caveolin-1.
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Affiliation(s)
- Xinxing Wang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, China
| | - Mingze Ma
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, China
| | - Lichao Zhu
- Department of Pediatric Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong Province, China
| | - Chuan Qin
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong Province, China
| | - Shuai Shao
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, China
| | - Xianwen Xu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, China
| | - Ruxin Gao
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, China
| | - Zhenhai Zhang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong Province, China.
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Chen H, Lin L, Zou L, Guo S, Qiu X, Ma K. NXT629 Ameliorates Cholesterol Gallstones in Mice Model by Improving Lipid Metabolism Disorder and Cholesterol Homeostasis Through Inhibiting the GPAM Pathway. Dig Dis Sci 2025; 70:612-621. [PMID: 39724467 PMCID: PMC11839818 DOI: 10.1007/s10620-024-08798-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND NXT629, a PPAR-alpha antagonist, exerts widespread effects in many diseases; however, its function and relevant mechanism in cholesterol gallstones (CG) remain largely unknown. METHODS Male C57BL/6 J mice were fed a regular diet or lithogenic diet (LD), followed by treatment with intraperitoneal injection of NXT629. H&E staining was performed to analyze hepatic pathological changes, and Oil red O staining was conducted to detect lipid accumulation. Concentrations of total cholesterol (TC), triglyceride (TG), phospholipids (PL), total bile acids (TBA), and cholesterol saturation index (CSI) in both bile and serum were analyzed using commercially available kits. The mRNA expressions of ABCG5/8, CYP7A1, CYP7B1, PPAR-α, and ABCB11 in mouse liver tissues were measured by qRT-PCR assay. Overexpression of glycerol-3-phosphate acyltransferase mitochondrial (GPAM) was constructed to investigate the molecular mechanism of NXT629 in CG. RESULTS NXT629 could prevent the formation of cholesterol gallstones (CG) and improve lipid metabolic disorders in mice fed a lithogenic diet (LD). Treatment with NXT629 significantly reduced the levels of ABCG5, ABCG8, and ABCB11, while increasing the levels of CYP7A1 and CYP7B1 in the LD group. Additionally, NXT629 treatment downregulated GPAM expression in hepatic tissue from LD-fed mice. Overexpression of GPAM partially counteracted the beneficial effects of NXT629 on CG formation, lipid metabolic disorders, and lipid-related gene expressions. CONCLUSION NXT629 can inhibit CG formation, improve lipid metabolism disorders and cholesterol homeostasis by inhibiting GPAM expression, suggesting that NXT629 may serve as a potential therapeutic strategy for cholesterol stones prevention and treatment.
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MESH Headings
- Animals
- Male
- Gallstones/metabolism
- Gallstones/prevention & control
- Cholesterol/metabolism
- Cholesterol/blood
- Mice, Inbred C57BL
- ATP Binding Cassette Transporter, Subfamily G, Member 8/metabolism
- ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics
- ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics
- ATP Binding Cassette Transporter, Subfamily G, Member 5/metabolism
- Homeostasis
- Mice
- Liver/metabolism
- Liver/drug effects
- Liver/pathology
- Disease Models, Animal
- Lipid Metabolism/drug effects
- ATP Binding Cassette Transporter, Subfamily B, Member 11/metabolism
- ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics
- Lipid Metabolism Disorders/metabolism
- Cytochrome P450 Family 7/metabolism
- Cytochrome P450 Family 7/genetics
- Cholesterol 7-alpha-Hydroxylase/metabolism
- Cholesterol 7-alpha-Hydroxylase/genetics
- Bile Acids and Salts/metabolism
- Signal Transduction/drug effects
- Steroid Hydroxylases/metabolism
- Steroid Hydroxylases/genetics
- Lipoproteins/metabolism
- PPAR alpha
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Affiliation(s)
- Hao Chen
- Huadu District People's Hospital of Guangzhou, Huadu District, No. 48 Xinhua Road, Guangzhou, 510800, China.
| | - Liang Lin
- Huadu District People's Hospital of Guangzhou, Huadu District, No. 48 Xinhua Road, Guangzhou, 510800, China
| | - Laibin Zou
- Huadu District People's Hospital of Guangzhou, Huadu District, No. 48 Xinhua Road, Guangzhou, 510800, China
| | - Shenglan Guo
- Huadu District People's Hospital of Guangzhou, Huadu District, No. 48 Xinhua Road, Guangzhou, 510800, China
| | - Xubin Qiu
- Huadu District People's Hospital of Guangzhou, Huadu District, No. 48 Xinhua Road, Guangzhou, 510800, China
| | - Keqiang Ma
- Huadu District People's Hospital of Guangzhou, Huadu District, No. 48 Xinhua Road, Guangzhou, 510800, China
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Liu Y, Li H, Sun T, Sun G, Jiang B, Liu M, Wang Q, Li T, Cao J, Zhao L, Xiao F, Zhao F, Cui H. Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics. IMETA 2025; 4:e70000. [PMID: 40027485 PMCID: PMC11865347 DOI: 10.1002/imt2.70000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 01/15/2025] [Accepted: 01/21/2025] [Indexed: 03/05/2025]
Abstract
Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.
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Affiliation(s)
- Ye Liu
- Peking University Fifth School of Clinical MedicineBeijing Hospital, National Center of GerontologyBeijingChina
- Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesBeijingChina
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesBeijingChina
| | - Hexin Li
- Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesBeijingChina
| | - Tianhan Sun
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Gaoyuan Sun
- Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesBeijingChina
| | - Boyue Jiang
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Meilan Liu
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Qing Wang
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Tong Li
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Jianfu Cao
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Li Zhao
- Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina
| | - Fei Xiao
- Peking University Fifth School of Clinical MedicineBeijing Hospital, National Center of GerontologyBeijingChina
- Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesBeijingChina
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesBeijingChina
| | - Fangqing Zhao
- Institute of Zoology, Chinese Academy of SciencesBeijingChina
- Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, Beijing Institutes of Life ScienceChinese Academy of SciencesBeijingChina
| | - Hongyuan Cui
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
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7
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Sarı İ, Bolat H, Özmen E, Köse B, Ayan D. Effect of laparoscopic cholecystectomy on plasma levels of EETs, arachidonic acids derived lipid mediators. Postgrad Med J 2025:qgae175. [PMID: 39883024 DOI: 10.1093/postmj/qgae175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 10/04/2024] [Accepted: 11/10/2024] [Indexed: 01/31/2025]
Abstract
BACKGROUND Epoxyeicosatrienoic acids (EETs) are closely associated with lipoprotein metabolism, and changes in lipid profiles potentially affect their levels and functions. Given the alterations in lipid metabolism after cholecystectomy, this study aimed to investigate the levels of four EET regioisomers (free and esterified) and lipid profiles in patients with cholelithiasis after laparoscopic cholecystectomy (LC) and explore correlations between these parameters. METHODS This prospective study involved 40 patients with symptomatic cholelithiasis who underwent LC. Plasma EETs and serum total cholesterol, triglyceride, high-density lipoprotein (HDL), very low-density lipoprotein, low-density lipoprotein, and body mass index (BMI) values were determined preoperatively and after 6 months of LC. RESULTS After LC, triglyceride and very low-density lipoprotein levels increased while TC decreased. BMI values increased significantly after the operation. Despite plasma EET levels decreasing remarkably after surgery, this change did not reach statistical significance. A significant correlation was observed between preoperative levels of 8,9- and 11,12-EET and pre-and post-operative HDL. There was a significant negative correlation between the EET levels measured before and after surgery and the change in BMI values. CONCLUSIONS In this study, we observed significant changes in lipid profile 6 months after LC. While HDL, low-density lipoprotein, and EET levels showed a decreasing trend post-surgery, this change was not statistically significant. This trend and their significant correlations may indicate a complex relationship between HDL and EET metabolism. In addition, the negative correlation between EET levels and BMI changes highlights the need for further research to elucidate the metabolic impact and weight regulation of EETs after LC.
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Affiliation(s)
- İsmail Sarı
- Department of Medical Biochemistry, Faculty of Medicine, Kırklareli University, Kırklareli, 39000, Turkey
| | - Hacı Bolat
- Department of General Surgery, Private Niğde Hayat Hospital, Niğde, 51000, Turkey
| | - Esma Özmen
- Department of Medical Biochemistry, Faculty of Medicine, Niğde Omer Halisdemir University, Niğde, 51000, Turkey
| | - Burcu Köse
- Department of Biotechnology, Faculty of Arts and Sciences, Niğde Ömer Halisdemir University, Niğde, 51000, Turkey
| | - Durmuş Ayan
- Department of Medical Biochemistry, Faculty of Medicine, Niğde Omer Halisdemir University, Niğde, 51000, Turkey
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8
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He M, Gu R, Huang X, Zhao A, Liu F, Zheng Y. Age-period-cohort analysis of gallbladder and biliary diseases epidemiological trends from 1990 to 2021 and forecasts for 2035: a systematic analysis from the global burden of disease study 2021. BMC Gastroenterol 2025; 25:7. [PMID: 39780071 PMCID: PMC11715995 DOI: 10.1186/s12876-025-03592-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 01/03/2025] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Gallbladder and biliary diseases (GABD) represent prevalent disorders of the digestive system. METHODS Data on age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (DALYs) rate (ASDR) were extracted from the Global Burden of Disease (GBD) 2021 study. The estimated annual percentage change (EAPC) was utilized to quantify temporal trends in GABD. Age-period-cohort analysis was conducted to determine the effects attributable to age, period, and birth cohort. Additionally, we projected global trends to 2035. RESULTS Globally, GABD incident cases, mortality cases, and DALYs increased by 60.11%, 71.71%, and 56.90%, respectively. However, all corresponding age-standardized rates (ASRs) demonstrated overall downward trends with estimated annual percentage changes (EAPC) of -0.32 (-0.38 to -0.26), -0.95 (-1.08 to -0.83), and - 0.69 (-0.74 to -0.65), respectively. The number of incident cases was higher in females than in males across all age groups. The age effect indicated that older individuals had higher age-specific incidence and death rates. Both period and cohort effects showed declining risk across incidence and mortality. The ASIR and ASMR of GABD are projected to continue decreasing over the next 15 years. CONCLUSION GABD continue to pose a significant global public health challenge, particularly affecting women and the elderly population. Consequently, the implementation of effective interventions to mitigate the GABD burden is of paramount importance.
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Affiliation(s)
- Maolang He
- Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, No.107 North Second Road, Hongshan Street, Shihezi, 832008, China
| | - Ruru Gu
- Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, No.107 North Second Road, Hongshan Street, Shihezi, 832008, China
| | - Xin Huang
- School of Medicine, Shihezi University, No.107 North Second Road, Hongshan Street, Shihezi, 832000, China
| | - Aifang Zhao
- School of Medicine, Shihezi University, No.107 North Second Road, Hongshan Street, Shihezi, 832000, China
| | - Fang Liu
- Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, No.107 North Second Road, Hongshan Street, Shihezi, 832008, China.
| | - Yong Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, No.107 North Second Road, Hongshan Street, Shihezi, 832008, China.
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9
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Wang J, Shen Z, Liang Y, Qin C, Chen S, Shi R, Huang Y, Chen X, Luo H, Yang P, Gong J, Zeng X, Wang D. Association of neutrophil percentage to albumin ratio with gallstones: a cross-sectional study from the United States NHANES. BMC Public Health 2024; 24:3503. [PMID: 39696262 PMCID: PMC11657001 DOI: 10.1186/s12889-024-21071-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 12/11/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND AND OBJECTIVE The neutrophil percentage to albumin ratio (NPAR) is an emerging, costimulatory indicator of inflammation that is associated with a variety of diseases, such as non-alcoholic fatty liver disease, liver fibrosis, stroke, and cardiovascular disease. However, the relationship between NPAR and gallstones (GS) has not yet been explored. Therefore, this study aimed to evaluate the association of the NPAR with the odds of GS and the age of patients at the time of their first GS surgery. METHODS Participants were selected from the National Health and Nutrition Examination Survey (NHANES) in the United States, a nationally representative survey. Logistic regression analysis and dose-response curve were performed to analyze the relationship between NPAR and the prevalence of GS. Multiple linear regression analysis and dose-response curve were used to analyze the association between NPAR and the age of patients at the time of their first GS surgery. Subgroup analyses further explored the relationships between NPAR and age, sex, race, body mass index, hypertension, and diabetes. RESULTS In total, 7805 adults aged > 20 years were included in this study, of whom 838 had a history of GS. After adjusting for all potential confounders, each 1-unit increase in NPAR was found to be associated with a 4% increase in the prevalence of GS (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02, 1.07) and an advancement in the age of the patient at the time of the first GS surgery by 0.35 years (β = - 0.35, 95% CI: - 0.68, - 0.02). Dose-response curves further confirmed that NPAR was positively associated with the prevalence of GS and negatively associated with the age of patients at the time of their first GS surgery. The results of the subgroup analyses suggested that after adjusting for all potential confounders, the positive association of NPAR with the prevalence of GS was more pronounced in the 40-59-year-old (OR: 1.07, 95% CI: 1.02, 1.12), male (OR: 1.07, 95% CI: 1.02, 1.12), non-Hispanic Black (OR: 1.06, 95% CI: 1.01, 1.12), non-hypertensive (OR: 1.06, 95% CI: 1.02, 1.10), and non-diabetic populations (OR=: 1.05, 95% CI: 1.02, 1.08). CONCLUSIONS The higher the NPAR, the higher the prevalence of GS, and the earlier the age of the patient at the time of the first GS surgery. Due to the nature of cross-sectional study, it is not possible to determine a causal relationship between them.
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Affiliation(s)
- Jianjun Wang
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
- NHC Key Laboratory of Nuclear Technology Medical Transformation, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Zhiwen Shen
- Department of Hepatobiliary and Pancreatic Surgery, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, 317000, China
| | - Yuwen Liang
- Department of Oncology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Chuan Qin
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Sirui Chen
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Ruizi Shi
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Yu Huang
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Xi Chen
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Hua Luo
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Pei Yang
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Jianping Gong
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
| | - Xintao Zeng
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China.
| | - Decai Wang
- NHC Key Laboratory of Nuclear Technology Medical Transformation, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China.
- Department of Urology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China.
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Xiao Y, Zhao W, Zhao Q, Pang K, Gao Q, Yang X, Chen H, Xu H. Exploring the association between life's essential 8 and gallstone disease in the US adult population: a population-based study utilizing NHANES data from 2017-2018. BMC Gastroenterol 2024; 24:453. [PMID: 39695408 DOI: 10.1186/s12876-024-03545-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 11/28/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Gallstones are a prevalent health issue, with established risk factors such as diet body mass index (BMI) and physical activity. However, the role of Life's Essential 8 (LE8), a composite measure of health behaviors and biological markers, in predicting gallstone risk remains unclear. This study aims to examine the association between LE8 scores and gallstone prevalence in a U.S. adult population. METHODS A cross-sectional analysis was conducted on 2836 adults. LE8 scores were categorized into tertiles, and multivariable logistic regression models assessed the relationship between LE8 and gallstones, with additional nonlinear assessment using restricted cubic spline analysis. RESULTS Gallstones prevalence was 10.37%, decreasing with higher LE8 scores. The multivariable analysis showed participants in higher LE8 tertiles had significantly lower gallstone risks compared to the lowest tertile. The spline analysis confirmed a significant nonlinear inverse association between LE8 and gallstone risk. CONCLUSIONS Higher LE8 scores correlate with a lower prevalence of gallstones, suggesting the potential of LE8 as a predictor of gallstone risk. This emphasizes the value of promoting LE8 components in public health initiatives to reduce gallstone prevalence and medical burden.
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Affiliation(s)
- Yi Xiao
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China
| | - Wenting Zhao
- Development Planning Department, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China
| | - Qiuchan Zhao
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China
| | - Kangfeng Pang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China
| | - Qiaoping Gao
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China
| | - Xiaoqu Yang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China
| | - Huadi Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
| | - Hao Xu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
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11
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Yu J, Meng Z, Liu X, Zheng Y, Xue D, Hao C, Wang L. Lipopolysaccharide in Bile Promotes the Neutrophil Extracellular Traps-Induced Gallstone Formation by Activating the Gallbladder Immune Barrier. Immunotargets Ther 2024; 13:789-803. [PMID: 39712952 PMCID: PMC11662912 DOI: 10.2147/itt.s495095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 12/03/2024] [Indexed: 12/24/2024] Open
Abstract
Background Cholelithiasis areis a common digestive system disorder, with cholesterol gallstones being the most prevalent type. Gallstones lead to many severe complications, posing a significant burden on global healthcare systems. Many studies have shown associations between biliary microbiota, gallbladder immune microenvironment, and gallstone formation. However, the specific immune mechanisms underlying the cholesterol gallstone formation have not been fully elucidated. Methods In this study, gallbladderand bile samples from 8 asymptomatic patients with cholelithiasis undergoing cholecystectomy and 11 healthy liver transplant donors were collected for tissue transcriptome sequencing and differential analysis. Male C57BL/6J mice were fed a normal or lithogenic diet for 6 weeks. Starting from the third week, lipopolysaccharide (LPS) or specific regulators were injected intraperitoneally once a week for a total of 3 times. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence were employed for quantitative, qualitative or localization analysis of LPS, neutrophil extracellular traps (NETs), inflammatory factors, proteins, and mRNAs using samples collected from mice. Results In patients with cholelithiasis, the gallbladder mechanical barrier is impaired, resulting in an immune-activated state. LPS induces damage to the gallbladder mucosal mechanical barrier through the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, it stimulates the continuous production of NETs through the TLR4/Phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, aggravating the formation of gallstones. Conclusion With the biliary dysbiosis, excessive LPS can invade the submucosa of the gallbladder, leading to chronic inflammation that recruits neutrophils to form NETs, which are ultimately expelled into bile, thereby promoting the formation of gallstones.
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Affiliation(s)
- Jingjing Yu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’ s Republic of China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China
| | - Ziang Meng
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’ s Republic of China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China
| | - Xuxu Liu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’ s Republic of China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China
| | - Yi Zheng
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’ s Republic of China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China
| | - Dongbo Xue
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’ s Republic of China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China
| | - Chenjun Hao
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’ s Republic of China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China
| | - Liyi Wang
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’ s Republic of China
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China
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12
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Byeon H. Insights from exploring the interrelated dynamics of gallstone disease, non-alcoholic fatty liver disease, and kidney stone disease. World J Gastroenterol 2024; 30:4977-4982. [PMID: 39679311 PMCID: PMC11612707 DOI: 10.3748/wjg.v30.i46.4977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/23/2024] [Accepted: 11/05/2024] [Indexed: 11/21/2024] Open
Abstract
This article delved into the comprehensive study by Jiang et al, which meticulously examined the bidirectional relationships among gallstone disease, non-alcoholic fatty liver disease, and kidney stone disease through a multicenter study, systematic review, and meta-analysis. The study provides significant evidence supporting these associations, offering valuable insights into the etiology and potential prevention strategies for these interconnected conditions. The clinical significance of these bidirectional relationships is profound, as they underscore the importance of recognizing these conditions not only as isolated diseases but as part of a complex network that can influence each other. These results highlight the critical need for thorough screening and personalized prevention strategies for individuals with these interconnected conditions. Explicit implications for prevention strategies and early screening practices are crucial, as they can lead to early detection and intervention, significantly altering disease progression and outcomes. Furthermore, identifying potential therapeutic targets within these shared pathways may enhance treatment efficacy and patient outcomes, making this research highly relevant to clinical practice. By comprehending the common pathophysiological mechanisms and applying specific interventions, healthcare professionals can greatly enhance patient care and lessen the impact of these widespread diseases on global health.
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Affiliation(s)
- Haewon Byeon
- Department of Digital Anti-aging Healthcare (BK21), Inje University, Gimhae 50834, South Korea
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13
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Zhuang Q, Cheng J, Wu S, Shen S, Huang D, Ning M, Xia J, Dong Z, Wan X. Association between sleep and gallstone disease in United States adults: A cross-sectional study. BMC Public Health 2024; 24:3291. [PMID: 39592967 PMCID: PMC11600586 DOI: 10.1186/s12889-024-20824-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 11/21/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Both gallstone disease and sleep disorders are important public health problems. Few studies to date have investigated the associations between sleep and gallstone disease in humans. This study aimed to assess whether sleep factors (sleep time, sleep amounts, trouble sleeping) were associated with gallstone disease in the United States adults. METHODS This was a population-based cross-sectional study of US adults, which included data of participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES) gathered between 2017 and March 2020. The assessment of gallstone disease and sleep factors was based on self-reported data. We used sample-weighted logistic regression and restricted cubic spline models to explore the associations between sleep factors and gallstone disease. Subgroup analyses were conducted to assess the interaction between trouble sleeping and interacting factors. RESULTS The prevalence of gallstone disease was 11% among the 9,210 adult participants. Going to bed late on weekdays (OR, 1.41; 95% CI, 1.15 to 1.74) and weekends (OR, 1.43; 95% CI, 1.14 to 1.78), and short sleep duration on weekdays (OR, 1.29; 95% CI, 1.00 to 1.68) were factors associated with increased risk of gallstone disease, and we detected dose-response associations with the restricted cubic spline model (RCS) models, after adjusting for confounders. Presenting trouble sleeping was associated with increased risk of gallstone disease (OR, 1.52; 95% CI, 1.03 to 2.23) and the association was influenced by the presence of thyroid disease (P for interaction = 0.037). CONCLUSIONS Our study results indicate that going to bed late, short sleep duration, and trouble sleeping were associated with increased risk of gallstone disease in a nationally representative sample of adults in the US.
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Affiliation(s)
- Qian Zhuang
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Jinnian Cheng
- Digestive Endoscopy Center, Tongren Hospital, Shanghai Jiaotong University School of Medicine, No. 1111 Xianxia Road, Shanghai, 200336, China
| | - Shan Wu
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Shuang Shen
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Dan Huang
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Min Ning
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Jie Xia
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Zhixia Dong
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China.
| | - Xinjian Wan
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China.
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Zhang Q, Li Y, Hu H, Tian M, Cao T, Wu H, Wu W, Zhang G. Serum arsenic augments gallstone risk in Henan rural cohort with multiple metal exposure. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 952:175991. [PMID: 39236814 DOI: 10.1016/j.scitotenv.2024.175991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/31/2024] [Accepted: 08/31/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND People are exposed to metals in various ways during their daily lives. However, the association between metal exposure and gallstones remains unclear. OBJECTIVES To investigate the relationship between serum elemental concentrations and the risk of gallstones. METHODS Participants (n = 4204) were drawn from the Henan Rural Cohort. Gallstone diagnosis was based on abdominal ultrasound reports during follow-up. Baseline serum elemental concentrations were measured using inductively coupled plasma mass spectrometry. The relationship between serum elemental levels and gallstones was evaluated using robust Poisson regression, restricted cubic spline (RCS), quantile g-computation (Qgcomp), grouped weighted quantile sum (GWQS) and Bayesian kernel machine regression (BKMR). RESULTS 121 individuals were diagnosed with gallstone (incidence rate of 2.88 %). In robust Poisson regression, after adjusting for confounding factors, the highest quartile of arsenic concentration compared to the lowest quartile had a 1.90 times higher relative risk (RR) [95 % confidence interval (CI): 1.05, 3.44]. Conversely, the highest quartile of zinc concentration compared to the lowest quartile had a 0.50 times lower RR (95 % CI: 0.28, 0.89). RCS showed an approximately "S"-shaped nonlinear relationship between serum arsenic levels and gallstones, with increasing arsenic concentration leading to a higher risk of gallstones; however, the risk plateaued when arsenic concentration exceeded 0.62 μg/L. Both the Qgcomp and GWQS indicated that arsenic plays a significant role in increasing the risk of gallstones, whereas zinc plays a significant role in reducing the risk of gallstones. BKMR showed that raising arsenic exposure from the 25th to the 75th percentile increased the risk of gallstones, while raising serum zinc concentration reduced it. CONCLUSIONS Higher serum arsenic concentration increases the risk of gallstones, whereas higher zinc concentration may reduce the risk. Effective prevention of gallstones may require further reduction of arsenic exposure and appropriate increases in zinc intake.
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Affiliation(s)
- Qian Zhang
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Yating Li
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Han Hu
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Meichen Tian
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Tingting Cao
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Hui Wu
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Weidong Wu
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
| | - Guofu Zhang
- School of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
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15
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Jiang Z, Jiang H, Zhu X, Zhao D, Su F. The relationship between high-sensitivity C-reactive protein and gallstones: a cross-sectional analysis. Front Med (Lausanne) 2024; 11:1453129. [PMID: 39600934 PMCID: PMC11588438 DOI: 10.3389/fmed.2024.1453129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
Background and objective High-sensitivity C-reactive protein (hs-CRP), a classical indicator of inflammation, holds significant clinical value in various diseases. The relationship between hs-CRP and gallstones, however, remains poorly studied at present. The relationship between hs-CRP and gallstones will be investigated in this study. Methods Data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) were analyzed, focusing on participants aged 20 years and older who provided complete hs-CRP and gallstone information. Due to the skewed distribution of hs-CRP, the data were log-transformed [Log (hs-CRP)] to achieve normalization. Logistic regression analysis, subgroup analysis, and smoothed fitted curves were applied to determine the relationship between Log (hs-CRP) and the presence of gallstones. Results The study included 4,484 participants with an average Log (hs-CRP) of 1.18 ± 0.74. The prevalence of gallstones was 11.15%, increasing with higher Log (hs-CRP) levels (quartile 1: 8.31%; quartile 2: 8.76%; quartile 3: 11.98%; quartile 4: 16.36%; p < 0.0001). Adjusting for all covariates in Model 3, each 10-fold increase in hs-CRP [corresponding to a one-unit increase in log10 (hs-CRP)] corresponded to a 29% increased odds of gallstones prevalence [1.29 (1.12-1.49)]. The smoothed fitted curve showed a positive linear relationship between Log (hs-CRP) and gallstones prevalence. The results of subgroup analyses exhibited a more pronounced positive correlation in the 20-40 age group [1.70 (1.33, 2.16)], compared to those aged 40-60 years [1.22 (1.01, 1.48)], and 60-80 years [1.14 (0.98, 1.34)]. Conclusion Higher Log (hs-CRP) levels are linked to a greater prevalence of gallstones. We still need to carry out further large prospective research to explore the causal relationship of this association.
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Affiliation(s)
- Zhimeng Jiang
- Graduate School of Hebei North University, Zhangjiakou, China
- Department of Gastroenterology, Air Force Medical Center, Chinese People's Liberation Army, Beijing, China
| | - Huixin Jiang
- School of Clinical Medicine, Haiyuan College of Kunming Medical University, Kunming, China
| | - Xingyu Zhu
- Graduate School of Hebei North University, Zhangjiakou, China
- Department of Cardiovascular Medicine, Air Force Medical Center, Chinese People's Liberation Army, Beijing, China
| | - Donglin Zhao
- Graduate School of Hebei North University, Zhangjiakou, China
- Department of Gastroenterology, Air Force Medical Center, Chinese People's Liberation Army, Beijing, China
| | - Feifei Su
- Department of Cardiovascular Medicine, Air Force Medical Center, Chinese People's Liberation Army, Beijing, China
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16
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Sheibani A, Reihani H, shoja A, Gharibvand MM, Hanafi MG. Gallstones increase the risk of nonalcoholic fatty liver: A case-control study. Health Sci Rep 2024; 7:e70068. [PMID: 39507675 PMCID: PMC11538031 DOI: 10.1002/hsr2.70068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 08/21/2024] [Accepted: 08/26/2024] [Indexed: 11/08/2024] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) and gallstones are generally seen together, and many of the risk factors for fatty liver and gallstones are common and similar. Therefore, this study aims to investigate the relationship between NAFLD and gallstones. Methods This case-control study was conducted in patients referred to Imam Khomeini and Golestan hospitals of Ahvaz University of Medical Sciences in 2023, whose ultrasound showed fatty liver. Patients who were diagnosed with NAFLD by ultrasound were considered as the case group, and patients who did not have diagnostic findings of fatty liver in ultrasound were considered as the control group. Finally, the information recorded in the checklists was statistically analyzed using SPSS version 26 (SPSS Inc.). Results Three hundred patients were included in our study, 150 as cases and 150 as controls. There was no significant difference between the groups in terms of gender and age (gender P-value: 0.817/age P-value: 0.102). A statistically significant relationship was found between obesity, diabetes mellitus (DM), the presence of gallstones, and NAFLD (weight p-value < 0.001/DM p-value < 0.001/gallstones P-value: 0.03). In addition, based on binary logistic regression analysis, the presence of gallstones increases the odds of NAFLD by 2.33 times (P-value: 0.035). Furthermore, having DM and increasing each BMI unit increases the odds of NAFLD by 16 times and 30%, respectively (BMI p-value < 0.001/DM p-value < 0.001). Conclusion Based on the results of our study, gallstones are an important risk factor for NAFLD. The possible mechanisms are the existence of common risk factors between gallstones and NAFLD and the reduction of motility and flow of bile in the bile ducts with the presence of gallstones.
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Affiliation(s)
- Abdolreza Sheibani
- Department of Radiology, School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
| | - Hamid Reihani
- School of MedicineShiraz University of Medical SciencesShirazIran
| | - Ahmad shoja
- Department of Radiology, School of MedicineSouth Khorasan University of Medical Sciences, Imam Reza HospitalBirjandIran
| | - Mohammad M. Gharibvand
- Department of Radiology, School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
| | - Mohammad G. Hanafi
- Department of Radiology, School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
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17
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Jing X, Ma Y, Li D, Zhang T, Xiang H, Xu F, Xia Y. Integration of bile proteomics and metabolomics analyses reveals novel insights into different types of gallstones in a high-altitude area. BMC Gastroenterol 2024; 24:330. [PMID: 39350090 PMCID: PMC11440720 DOI: 10.1186/s12876-024-03422-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 09/16/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND To explore the pathogenesis of different subtypes of gallstones in high-altitude populations from a molecular perspective. METHODS We collected bile samples from 20 cholesterol gallstone disease (CGD) patients and 20 pigment gallstone disease (PGD) patients. Proteomics analysis was performed by LC/MS DIA, while metabolomics analysis was performed by UPLC- Q-TOF/MS. RESULTS We identified 154 up-regulated and 196 down-regulated differentially expressed proteins, which were significantly enriched in neurodegenerative diseases, energy metabolism, amino acid metabolism etc. In metabolomics analysis, 20 up-regulated and 63 down-regulated differentially expressed metabolites were identified, and they were significantly enriched in vitamin B6 metabolism. Three pathways of integrated proteomics and metabolomics were significantly enriched: porphyrin and chlorophyll metabolism, riboflavin metabolism and aminoacyl-tRNA biosynthesis. Remarkably, 7 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers. CONCLUSION The findings of our metabolomics and proteomics analyses help to elucidate the underlying mechanisms of gallstone formation in high-altitude populations.
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Affiliation(s)
- Xiaofeng Jing
- Department of Evidence-Based Medicine and Social Medicine, School of Public Health, Chengdu Medical College, Xindu avenue 783, Chengdu, Sichuan, 610500, China
| | - Ying Ma
- Department of Hepatobiliary Surgery, Qinghai Provincial Traffic Hospital, Traffic lane 7, Xining, 810001, China
| | - Defu Li
- Department of Hepatobiliary Surgery, Qinghai Provincial Traffic Hospital, Traffic lane 7, Xining, 810001, China
| | - Tiecheng Zhang
- Department of Evidence-Based Medicine and Social Medicine, School of Public Health, Chengdu Medical College, Xindu avenue 783, Chengdu, Sichuan, 610500, China
| | - Haiqi Xiang
- Department of Evidence-Based Medicine and Social Medicine, School of Public Health, Chengdu Medical College, Xindu avenue 783, Chengdu, Sichuan, 610500, China
| | - Fan Xu
- Department of Evidence-Based Medicine and Social Medicine, School of Public Health, Chengdu Medical College, Xindu avenue 783, Chengdu, Sichuan, 610500, China.
| | - Yonghong Xia
- Department of Hepatobiliary Surgery, Qinghai Provincial Traffic Hospital, Traffic lane 7, Xining, 810001, China.
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18
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Song Y, Wang H, Xu Y. Cholecystectomy and risk of cardiovascular disease, all-cause and cause-specific mortality: a systematic review and updated meta-analysis. PeerJ 2024; 12:e18174. [PMID: 39364358 PMCID: PMC11448656 DOI: 10.7717/peerj.18174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 09/04/2024] [Indexed: 10/05/2024] Open
Abstract
Objective Questions remain about the association among cholecystectomy, cardiovascular disease, all-cause and cause-specific mortality. We performed a systematic review and meta-analysis to clarify these associations. Methods PubMed, Web of Science, Embase, and Cochrane Library databases were searched up to February 2024. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a DerSimonian-Laird random effects model. Results We screened 16,595 articles and included 14 studies. No significant association was found between cholecystectomy and cardiovascular disease (CVD), with RR being 1.03 (95% CI [0.77-1.37], p = 0.848, I 2 = 99.6%), even in results with high heterogenous studies excluded (RR 1.20, 95% CI [0.97-1.49], p = 0.095, I 2 = 77.7%). Same result was proved in its subtype, coronary heart disease (RR 1.06, 95% CI [0.84-1.33], p = 0.633, I2 = 96.6%). Cholecystectomy increased CVD risk compared with healthy controls without gallstones (RR 1.19, 95% CI [1.05-1.35], p = 0.007, I 2 = 83.3%) and lowered CVD risk compared with gallstone carriers (RR 0.62, 95% CI [0.57-0.67], p < 0.001, I 2 = 82.1%). As for mortality, increase in the risk for all-cause (RR 1.17, 95% CI [1.03-1.34], p = 0.020, I 2 = 51.6%) and cardiovascular (RR 1.24, 95% CI [1.06-1.47], p = 0.009, I 2 = 20.7%) mortality, but not for cancer mortality (RR 1.18, 95% CI [0.95-1.47], p = 0.131, I 2 = 0.0%), were observed after cholecystectomy. Conclusion Cholecystectomy may not be associated with the overall development of CVD, as well as CHD. Cholecystectomized patients showed increased CVD risk compared with healthy controls without gallstones, but decreased CVD risk compared with gallstone patients. Increased risk for all-cause and cardiovascular, but not cancer mortality was observed following cholecystectomy.
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Affiliation(s)
- Yang Song
- Yantai Nurses School of Shandong, Yantai, China
| | - Haishu Wang
- Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong Province, China
| | - Yaowen Xu
- Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong Province, China
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19
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Wang H, Feng X, Huang Q, Zheng X. Association between lipid accumulation products and gallstones: an analysis of the National Health and Nutrition Examination Survey 2017-2020. BMC Gastroenterol 2024; 24:311. [PMID: 39285353 PMCID: PMC11406836 DOI: 10.1186/s12876-024-03410-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 09/09/2024] [Indexed: 09/19/2024] Open
Abstract
AIMS The aim of the research was to look into the connection between the occurrence of gallstones in adult US citizens and lipid accumulation products (LAP). METHODS We conducted a cross-sectional study of 3,582 U.S. adults with relevant indicators collected from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) database. Multifactorial logistic regression was used to investigate the linear relationship between LAP and gallstone incidence, while smoothed curve fitting was used to describe the nonlinear relationship, and subgroup and interaction analyses were used to evaluate the potential differences between groups. RESULTS Among the 3582 participants aged ≥ 20 years included, there was a positive association between LAP and gallstones. Following adjustments for all covariates, the likelihood of getting gallstones rose by 29% for each unit rise in log2-LAP (OR = 1.29, 95% CI: 1.13‒1.49). Compared to those in the lowest tertile, those in the highest LAP tertile had a significantly higher risk of developing gallstones (OR = 1.97, 95% CI: 1.31‒2.95). Subgroup analyses indicated that the association between LAP and gallstones was not affected by the stratification of the variables examined. CONCLUSION Gallstones and LAP exhibited a positive association in our investigation, indicating that LAP may be utilized as a clinical indicator to determine the occurrence of gallstones.
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Affiliation(s)
- Huimin Wang
- Department of Endocrinology, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230000, China
| | - Xiaojia Feng
- Department of Oncology, The First Affiliated Hospital of Anhui University of Science and Technology, Huainan, 232000, China
| | - Qihui Huang
- Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230000, China
| | - Xiaowei Zheng
- Department of Infection, Hospital for Infectious Diseases, Anhui Provincial Hospital, Hefei, 230000, China.
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20
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Liu X, Zhang Z, Wang H, Faisal S, He M, Tai S, Lin Y. The link between serum cotinine levels and gallstones prevalence in adults: a cross-sectional analysis using NHANES data (2017-2020). Front Nutr 2024; 11:1438170. [PMID: 39318386 PMCID: PMC11421389 DOI: 10.3389/fnut.2024.1438170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 08/30/2024] [Indexed: 09/26/2024] Open
Abstract
Background Gallstones represent a prevalent health issue globally, resulting in significant annual healthcare costs. While tobacco exposure is recognized for its association with numerous diseases, its correlation with gallstones remains contentious. Serum cotinine, a metabolite of nicotine, serves as a widely utilized indicator for assessing tobacco exposure. Crucially, no research has yet examined the association between serum cotinine levels and the gallstones. Methods This study is designed as a cross-sectional analysis, utilizing data from the NHANES public database. The relationship between serum cotinine levels and gallstones was analyzed using multinomial logistic regression models and smooth curve fitting. Subgroup analyses and interaction tests were performed to examine the potential contributions of different populations and covariates to the findings. Results A total of 5,856 participants were included in this study. After adjusting for relevant covariates, the multiple logistic regression model results indicated that for each unit increase in serum cotinine concentration above 0.29 ng/mL, there was a 29% increase in the prevalence of gallstones. Furthermore, smooth curve fitting analysis revealed a positive correlation between these variables. These findings underscore the impact of tobacco exposure on gallstone prevalence. Conclusion This study demonstrates a positive correlation between tobacco exposure, as measured by serum cotinine levels, and the prevalence of gallstones, thus adding to the body of existing research on this relationship.
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Affiliation(s)
- Xin Liu
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Zheng Zhang
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Haoran Wang
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Shah Faisal
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Meng He
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Sheng Tai
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yujia Lin
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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21
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Yang T, Zhong J, Zhang R, Xiao F, Wang Y, Tao H, Hong F. Different types and numbers metabolic abnormalities and risk of gallbladder stone disease in adults. Front Nutr 2024; 11:1443575. [PMID: 39315007 PMCID: PMC11416965 DOI: 10.3389/fnut.2024.1443575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 08/27/2024] [Indexed: 09/25/2024] Open
Abstract
Background Metabolic abnormalities in the body increase the risk of gallbladder stones and their complications, which brings a great economic and social burden. The relationship between different types and amounts of metabolic abnormalities and gallstone risk in different sexes is poorly documented and controversial. Methods Based on the baseline survey data of the Chinese Multi-Ethnic Cohort (CMEC) study, 4,075 Chinese adults aged 30-79 years with complete abdominal ultrasound results and metabolic index data. Logistic regression model was used to evaluate the correlation between five metabolic abnormalities and gallstones, and to explore the gender difference. Results The detection rate of gallbladder stones was found to be 7.0%, with a higher rate in women (8.6%) than in men (4.1%). Logistic results showed adjustment odds ratio (ORs) and 95% confidence interval (95% CI) of dysglycemia + hypertension + central obesity in 3 metabolic combinations was 4.459 (1.653, 12.029). The four metabolic combinations, dysglycemia + dyslipidemia + hypertension + central obesity, dysglycemia + dyslipidemia + hypertension + abnormal blood uric acid and dysglycemia + dyslipidemia + central obesity + abnormal blood uric acid adjusted OR and 95%CI were 3.342 (1.459, 7.659), 5.439 (1.555, 19.018) and 2.971 (1.187, 7.435), respectively. Gender-stratified analysis found that "any three or more metabolic abnormalities and their components were associated with gallstone risk, more significantly in women. Conclusion Different types and amounts of five metabolic abnormalities were associated with the risk of gallstone development, and the differences were more significant in women than men.
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Affiliation(s)
| | | | | | | | | | | | - Feng Hong
- School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China
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22
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Uche-Anya E, Ha J, Khandpur N, Rossato SL, Wang Y, Nguyen LH, Song M, Giovannucci E, Chan AT. Ultraprocessed food consumption and risk of gallstone disease: analysis of 3 prospective cohorts. Am J Clin Nutr 2024; 120:499-506. [PMID: 38971469 PMCID: PMC11393404 DOI: 10.1016/j.ajcnut.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 06/04/2024] [Accepted: 07/01/2024] [Indexed: 07/08/2024] Open
Abstract
BACKGROUND Majority of dietary intake in United States adults comes from ultraprocessed foods (UPFs), which have been linked to several adverse health outcomes. Gallstone disease is highly prevalent and constitutes a significant burden to the United States health system but remains understudied. OBJECTIVES This study aimed to investigate the association between UPF consumption and incident gallstone disease risk. METHODS In this analysis, 44,149 males in the Health Professionals' Follow-up Study (HPFS: 1986-2022), 71,145 females in the Nurses' Health Study (NHS: 1986-2021), and 90,932 females in the NHS II (1991-2021) were prospectively followed. Dietary intake was quadrennially assessed with semiquantitative food frequency questionnaires and used to identify UPFs. The primary outcome was defined as cholecystectomy. Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS Baseline median age was 54 y in HPFS, 53 y in NHS, and 36 y in NHS II. We identified 32,374 incident gallstone disease cases over 5,077,059 person-years. Participants in the highest UPF quintile had a higher incidence of gallstone disease than those in the lowest quintile (aHR: 1.29; 95% CI: 1.24, 1.36; P < 0.001). Incremental risk of incident gallstone disease was 2.8% per daily serving (95% CI: 2.4%, 3.2%; P < 0.001). This risk was driven by sugar-sweetened beverages and artificially sweetened beverages on UPF subgroup analyses. The proportion of risk mediated by obesity was 12.8% (95% CI: 7.7%, 20.5%; P < 0.001) in HPFS, 14.3% (95% CI: 10.4%, 19.4%; P < 0.001) in NHS, and 39.4% (95% CI: 31.2%, 48.1%; P < 0.001) in NHS II. The partial population attributable risk was estimated at 15.9% (95% CI: 13.4%, 18.3%). CONCLUSIONS UPF consumption is associated with a higher risk of gallstone disease, particularly consumption of sugar-sweetened beverages and artificially sweetened beverages. A substantial proportion of this risk is potentially mediated by obesity in younger females.
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Affiliation(s)
- Eugenia Uche-Anya
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
| | - Jane Ha
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Neha Khandpur
- Division of Human Nutrition and Health, Wageningen University, Wageningen, Netherlands; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Sinara Laurini Rossato
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Laboratory of Research and Extension in Epidemiology and Health (Lapex-Epi), Institute of Geography, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil
| | - Yiqing Wang
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Long H Nguyen
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Mingyang Song
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Edward Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States
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23
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Uche-Anya E, Ha J, Balasubramanian R, Rexrode KM, Chan AT. Metabolomic profiles of incident gallstone disease. BMJ Open Gastroenterol 2024; 11:e001417. [PMID: 39209332 PMCID: PMC11367368 DOI: 10.1136/bmjgast-2024-001417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 07/26/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND AND AIMS Gallstone disease affects ≥40 million people in the USA and accounts for health costs of ≥$4 billion a year. Risk factors such as obesity and metabolic syndrome are well established. However, data are limited on relevant metabolomic alterations that could offer mechanistic and predictive insights into gallstone disease. This study prospectively identifies and externally validates circulating prediagnostic metabolites associated with incident gallstone disease. METHODS Female participants in Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II) who were free of known gallstones (N=9960) were prospectively followed up after baseline metabolomic profiling with liquid chromatography-tandem mass spectrometry. Multivariable logistic regression and enrichment analysis were used to identify metabolites and metabolite groups associated with incident gallstone disease at PFDR<0.05. Findings were validated in 1866 female participants in the Women's Health Initiative and a comparative analysis was performed with 2178 male participants in the Health Professionals Follow-up Study. RESULTS After multivariate adjustment for lifestyle and putative risk factors, we identified and externally validated 17 metabolites associated with incident gallstone disease in women-nine triacylglycerols (TAGs) and diacylglycerols (DAGs) were positively associated, while eight plasmalogens and cholesterol ester (CE) were negatively associated. Enrichment analysis in male and female cohorts revealed positive class associations with DAGs, TAGs (≤56 carbon atoms and ≤3 double bonds) and de novo TAG biosynthesis pathways, as well as inverse associations with CEs. CONCLUSIONS This study highlights several metabolites (TAGs, DAGs, plasmalogens and CE) that could be implicated in the aetiopathogenesis of gallstone disease and serve as clinically relevant markers.
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Affiliation(s)
- Eugenia Uche-Anya
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jane Ha
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Raji Balasubramanian
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, Massachusetts, USA
| | - Kathryn M Rexrode
- Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
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Li H, Zhang C. Association between triglyceride-glucose index and gallstones: a cross-sectional study. Sci Rep 2024; 14:17778. [PMID: 39090272 PMCID: PMC11294540 DOI: 10.1038/s41598-024-68841-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 07/29/2024] [Indexed: 08/04/2024] Open
Abstract
This study used data from the National Health and Nutrition Examination Survey (NHANES) to investigate the relationship between the triglyceride-glucose (TyG) index and gallstones. We evaluated the data collected between 2017 to 2020. To evaluate the relationship between TyG index and gallstones, logistic regression analysis, basic characteristics of participants, subgroup analysis, and smooth curve fitting were utilized. The study included 3870 participants over the age of 20 years, 403 of whom reported gallstones, with a prevalence rate of 10.4%. After adjusting for all confounding factors, the risk of gallstones increased by 41% for each unit increase in the TyG index (OR 1.41, 95% CI 1.07, 1.86). The smooth curve fitting also showed a positive correlation between the TyG index and gallstones. Subgroup analysis revealed a significant positive relationship between the TyG index and the risk of gallstones in those aged < 50 years, women, individuals with total cholesterol levels > 200 mg/dL, individuals with body mass index (BMI) > 25, and individuals without diabetes. The risk of gallstones is positively correlated with a higher TyG index. Thus, the TyG index can be used as a predictor of the risk of gallstones.
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Affiliation(s)
- Hongliang Li
- Department of General Surgery, Dandong Central Hospital, Dandong, China
| | - Congfeng Zhang
- Department of Intensive Care Unit, Dandong Central Hospital, Dandong, China.
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Kim NH, Kang JH, Kim HJ. Association between nonalcoholic fatty liver disease and gallstone risk in nonobese and lean individuals. Eur J Gastroenterol Hepatol 2024; 36:945-951. [PMID: 38652507 DOI: 10.1097/meg.0000000000002779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/25/2024]
Abstract
PURPOSE The association between nonobese/lean nonalcoholic fatty liver disease (NAFLD) and gallstone formation remains unclear. We aimed to assess whether NAFLD is an independent risk factor for gallstones, even in nonobese or lean individuals. METHODS We analyzed 265 353 asymptomatic adults who underwent abdominal ultrasonography. The risk of gallstone was assessed on the basis of obesity and NAFLD status. RESULTS The overall prevalence rates of NAFLD and gallstones were 27.1% and 2.6%, respectively. The prevalence rates of NAFLD among the 195 204 nonobese and 136 194 lean participants were 14.7% and 7.4%, respectively. Individuals with NAFLD had a significantly increased risk of gallstones (adjusted odds ratio [OR], 1.23; 95% confidence interval [CI], 1.14-1.32). Moreover, NAFLD significantly increased the risk of gallstone (adjusted OR, 1.29; 95% CI, 1.17-1.41) among nonobese individuals. Lean individuals with NAFLD also exhibited a significantly increased risk of gallstones (adjusted OR, 1.20; 95% CI, 1.03-1.40). Furthermore, these findings remained consistent even in nonobese and lean individuals without insulin resistance. CONCLUSION Nonobese/lean NAFLD is an independent risk factor for gallstone formation, suggesting its role in gallstone pathogenesis, regardless of obesity status. Therefore, when hepatic steatosis is detected on abdominal ultrasonography, a more thorough evaluation of the gallstones may be necessary, even in nonobese or lean individuals.
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Affiliation(s)
- Nam Hee Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul
| | - Ji Hun Kang
- Department of Radiology, Hanyang University College of Medicine, Hanyang University Guri Hospital, Guri, Republic of Korea
| | - Hong Joo Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul
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Wang Y, Jiang ZH, Zhou YW, Qiu TT, Wang H, Zhu MS, Chen X, Zhang XN. Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice. Hepatol Commun 2024; 8:e0473. [PMID: 38934703 PMCID: PMC11213606 DOI: 10.1097/hc9.0000000000000473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 04/19/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown. METHODS Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF). RESULTS Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF. CONCLUSIONS We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.
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Affiliation(s)
- Ye Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Zhi-Hui Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Yu-Wei Zhou
- Jiangsu Key Laboratory of Molecular Medicine, Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Tian-Tian Qiu
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Han Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Min-Sheng Zhu
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Xin Chen
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Xue-Na Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jinling Pharmaceutical Co., Ltd., Nanjing, China
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Yu JX, Jiang ZZ, Cai YH, Zhou L, Cai B. Follow-up study of gallbladder stones in 44 children. World J Clin Cases 2024; 12:3403-3409. [PMID: 38983392 PMCID: PMC11229927 DOI: 10.12998/wjcc.v12.i18.3403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/27/2024] [Accepted: 05/17/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Cholesterol stones affect a certain subpopulation of children. Concerns have been raised on the impact of gallbladder surgery on the growth of children and adolescents. AIM To study the population characteristics, clinical features, treatment, and prognosis of gallstones in children. METHODS The clinical data of 44 children with gallstones admitted to The First Affiliated Hospital of Naval Medical University from August 2009 to August 2021 were collected, the children were followed up by telephone to monitor their prognoses. The follow-up ended in August 2023. The shortest follow-up time was 2 years and 6 months, whereas the longest was 13 years and 11 months. The population characteristics, general clinical characteristics, and treatments were retrospectively analyzed. The children were divided according to whether they underwent surgical gallbladder removal into an operation group (n = 28) and a non-operation group (n = 16), The effects of surgical gallbladder resection on the growth and development of children were analyzed. RESULTS The male-female ratio in the population was 6:5 and 84.09% of the children had onset in adolescence. Furthermore, 29.55% of the children were overweight or obese. The study identified 26 cases with metabolic abnormalities, 9 with hemolytic anemia, and 4 with choledochal cyst. Of the population, 68.18% had recurrent symptomatic cholecystolithiasis. Surgical treatment accounted for 63.64%, with laparoscopic cholecystectomy accounting for 71.43% of surgical treatment. No significant differences were observed in symptoms and complications between the surgery and non-surgery groups. Furthermore, no significant differences were found between the two groups in the attainment of genetic height target and the rightward shift of height curve during follow-up. CONCLUSION The sex characteristics of gallstones in children were not observed. Most gallstones occurred in adolescents and rarely in young children. A considerable proportion of children have inborn causes, which are often concurrent with metabolic abnormalities and hemolytic anemia. Most children had recurrent symptomatic gallstones. Surgical treatment, especially laparoscopic cholecystectomy, is still the main treatment for gallstones in children. Surgical treatment did not affect the growth and development of children who underwent gallstone removal.
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Affiliation(s)
- Jian-Xiong Yu
- Department of Pediatric, The Firs Affiliated Hospital of Naval Medical University, Shanghai 20000, China
| | - Zhi-Zhong Jiang
- Department of Pediatric, The Firs Affiliated Hospital of Naval Medical University, Shanghai 20000, China
| | - Yuan-Hao Cai
- Department of Pediatric, The Firs Affiliated Hospital of Naval Medical University, Shanghai 20000, China
| | - Lin Zhou
- Department of Pediatric, The Firs Affiliated Hospital of Naval Medical University, Shanghai 20000, China
| | - Bin Cai
- Department of Pediatric, The Firs Affiliated Hospital of Naval Medical University, Shanghai 20000, China
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Georgescu D, Lighezan DF, Ionita I, Hadaruga N, Buzas R, Rosca CI, Ionita M, Suceava I, Mitu DA, Ancusa OE. Cholesterol Gallstones and Long-Term Use of Statins: Is Gut Microbiota Dysbiosis Bridging over Uncertainties? Diagnostics (Basel) 2024; 14:1234. [PMID: 38928650 PMCID: PMC11202934 DOI: 10.3390/diagnostics14121234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/21/2024] [Accepted: 05/25/2024] [Indexed: 06/28/2024] Open
Abstract
A total of 300 research participants-200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (-)) and 100 healthy controls-were included in this observational study. The aim of the study was to deliver insights into the relationship between the long-term use of statins for dyslipidemia and gallstone disease (GSD), as well as insights into the background particularities of the gut microbiota. All study participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, and abdominal ultrasound/CT exams. Results: The research participants presented with similarities related to age, gender, and location. Patients displayed comparable heredity for GSs, metabolic issues, and related co-morbidities. Gut dysbiosis (DB) was present in 54% of the statin (-) patients vs. 35% of the statin (+) patients (p = 0.0070). GSs were present in 14% of patients in the statin (-) group vs. 5% of patients in the statin (+) group (p = 0.0304). Severe dysbiosis, with a significant reduction in biodiversity, an increase in LPS (+) bacteria, and a notable decrease in mucin-degrading bacteria, mucosa-protective bacteria, and butyrate-producing bacteria were observed in the statin (-) group. Strong positive correlations between GSD and diabetes/impaired glucose tolerance (r = 0.3368, p = 0.0006), obesity (r = 0.3923, p < 0.0001), nonalcoholic fatty liver disease (r = 0.3219, p = 0.0011), and DB (r = 0.7343, p < 0.0001), as well as significant negative correlations between GSD and alcohol use (r = -0.2305, p = 0.0211), were observed. The multiple regression equation demonstrated that only DB (95% CI: 0.3163 to 0.5670; p < 0.0001) and obesity (95% CI: 0.01431 to 0.2578; p = 0.0289) were independent risk factors predicting GSD in the group of patients treated with statins. Conclusion: The long-term use of statins in dyslipidemic patients was associated with a low risk of developing GSs. The gut microbiota associated with a long-term use of statins in dyslipidemic patients was characterized by a low risk of developing an imbalance of various functional bacteria and alterations in the metabolic microbiota. DB and obesity were found to be independent risk factors predicting GSD in statin (+) patients.
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Affiliation(s)
- Doina Georgescu
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Daniel-Florin Lighezan
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Ioana Ionita
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Nicoleta Hadaruga
- Department of Food Science, University of Life Sciences “King Michael I”, 300041 Timisoara, Romania;
| | - Roxana Buzas
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Ciprian-Ilie Rosca
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Mihai Ionita
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Ioana Suceava
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Diana-Alexandra Mitu
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
| | - Oana-Elena Ancusa
- Department V of Internal Medicine I, “V Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.-F.L.); (R.B.); (C.-I.R.); (M.I.); (I.S.); (D.-A.M.); (O.-E.A.)
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Tang H, Zhang X, Huang J, Luo N, Chen H, Yang Q, Lin H, Hua H. Phthalate and gallstones: the mediation of insulin. Front Public Health 2024; 12:1401420. [PMID: 38903577 PMCID: PMC11188473 DOI: 10.3389/fpubh.2024.1401420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 05/23/2024] [Indexed: 06/22/2024] Open
Abstract
Background Exposure to a mixture of environmental chemicals may cause gallstone, but the evidence remains equivocal. The current study aims to investigate the association between phthalate metabolites and gallstones, and to explore their mediators. Methods Data from the National Health and Nutrition Examination Survey 2017-2018 on U.S. adults (≥20 years) were analyzed to explore the association between phthalate metabolites and gallstones by employed survey-weighted logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses examined the role of oxidative stress markers, inflammatory markers, metabolic syndrome, body composition, diabetes, and insulin. Results The current study included 1,384 participants, representing 200.6 million U.S. adults. Our results indicated a significant association between phthalate metabolites, particularly high molecular weight metabolites such as Di(2-ethylhexyl) phthalate (DEHP) and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), and gallstones. Furthermore, mediation analyses indicated that phthalate metabolites may play a role in the development of gallstones by influencing insulin secretion. Subgroup analyses did not reveal significant interaction. Conclusion The association between exposure to phthalates and the occurrence of gallstones, potentially mediated by hyperinsulinemia from a nationally representative epidemiological perspective. These insights contribute to a better understanding of the potential health implications of plasticizers, emphasizing the need for proactive management measures.
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Affiliation(s)
- Haoxian Tang
- Shantou University Medical College, Shantou, Guangdong, China
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Xuan Zhang
- Shantou University Medical College, Shantou, Guangdong, China
- Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Jingtao Huang
- Shantou University Medical College, Shantou, Guangdong, China
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Nan Luo
- Shantou University Medical College, Shantou, Guangdong, China
- Department of Psychiatry, Shantou University Mental Health Center, Shantou, Guangdong, China
| | - Hongyu Chen
- Shantou University Medical College, Shantou, Guangdong, China
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Qinglong Yang
- Shantou University Medical College, Shantou, Guangdong, China
- Department of Urology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Hanyuan Lin
- Shantou University Medical College, Shantou, Guangdong, China
- Department of Urology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Hao Hua
- Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliate Hospital of Guizhou Medical University, Guiyang, Guizhou, China
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30
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Chang TE, Huang KH, Luo JC, Huang YH, Lin HH, Fang WL, Hou MC. The alteration of fecal microbial and metabolic profile of gallstone patients in Taiwan: Single-center study. J Chin Med Assoc 2024; 87:572-580. [PMID: 38578093 DOI: 10.1097/jcma.0000000000001094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls. METHODS We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics. RESULT Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium , Prevotella 9 , and Bacteroides plebeius DSM 17135 . The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella . In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group ( p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness. CONCLUSION Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.
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Affiliation(s)
- Tien-En Chang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Endoscopic Center for Diagnosis and Therapy, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan, ROC
| | - Kuo-Hung Huang
- National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan, ROC
- Division of General Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Jiing-Chyuan Luo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan, ROC
| | - Hung-Hsin Lin
- National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan, ROC
- Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Wen-Liang Fang
- National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan, ROC
- Division of General Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan, ROC
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Turki A, Obaid AM, Bellaaj H, Ksantini M, AlTaee A. UIdataGB: Multi-Class ultrasound images dataset for gallbladder disease detection. Data Brief 2024; 54:110426. [PMID: 38708300 PMCID: PMC11068544 DOI: 10.1016/j.dib.2024.110426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 04/09/2024] [Accepted: 04/11/2024] [Indexed: 05/07/2024] Open
Abstract
Artificial Intelligence (AI) allows computers to self-develop decision-making algorithms through huge data analysis. In medical investigations, using computers to automatically diagnose diseases is a promising area of research that could change healthcare strategies worldwide. However, it can be challenging to reproduce or/and compare various approaches due to the often-limited datasets comprising medical images. Since there is no open access dataset for the Gallbladder (GB) organ, we introduce, in this study, a large dataset that includes 10,692 GB Ultrasound Images (UI) acquired at high resolution from 1,782 individuals. These UI include many disease types related to the GB, and they are organized around nine important anatomical landmarks. The data in this collection can be used to train machine learning (ML) and deep learning (DL) models for computer-aided detection of GB diseases. It can also help academics conduct comparative studies and test out novel techniques for analyzing UI to explore the medical domain of GB diseases. The objective is then to help move medical imaging forward so that patients get better treatment.
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Affiliation(s)
- Amina Turki
- CEMLab, National Engineering School of Sfax, University of Sfax, Tunisia
| | - Ahmed Mahdi Obaid
- National School of Electronics and Telecommunications of Sfax, University of Sfax, Tunisia
| | - Hatem Bellaaj
- ReDCAD, National Engineering School of Sfax, University of Sfax, Sfax 3029, Tunisia
| | - Mohamed Ksantini
- CEMLab, National Engineering School of Sfax, University of Sfax, Tunisia
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Turner RC, Salomoni S, Neale RE, Neil A, Barreto SG, Ooi CY, Croagh D, Wilson JS, Pang T, Apte M. The epidemiology of acute pancreatitis in Tasmania over a 12-year period: Is this a disease of disadvantage? Pancreatology 2024; 24:522-527. [PMID: 38704341 DOI: 10.1016/j.pan.2024.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 04/08/2024] [Accepted: 04/27/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND The global incidence of acute pancreatitis (AP) is increasing, but little information exists about trends in Australia. This study aimed to describe incidence trends, along with clinical and socio-demographic associations, in the state of Tasmania over a recent 12-year period. METHODS The study cohort was obtained by linking clinical and administrative datasets encompassing the whole Tasmanian population between 2007 and 2018, inclusive. Pancreatitis case definition was based on relevant ICD-10 hospitalization codes, or elevated serum lipase or amylase in pathology data. Age-standardised incidence rates were estimated, overall and stratified by sex, aetiology, and Index of Relative Socio-economic Disadvantage (IRSD). RESULTS In the study period, 4905 public hospital AP episodes were identified in 3503 people. The age-standardised person-based incidence rate across the entire period was 54 per 100,000 per year. Incidence was inversely related to IRSD score; 71 per 100,000 per year in the most disadvantaged quartile compared to 32 in the least disadvantaged. Biliary AP incidence was higher than that of alcohol-related AP, although the greatest incidence was in "unspecified" cases. There was an increase in incidence for the whole cohort (average annual percent change 3.23 %), largely driven by the two most disadvantaged IRSD quartiles; the least disadvantaged quartile saw a slight overall decrease. CONCLUSION This is the first Australian study providing robust evidence that AP incidence is increasing and is at the upper limit of population-based studies worldwide. This increased incidence is greatest in socio-economically disadvantaged areas, meriting further research to develop targeted, holistic management strategies.
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Affiliation(s)
- Richard C Turner
- Tasmanian School of Medicine, University of Tasmania, Hobart, Australia.
| | - Sauro Salomoni
- Tasmanian School of Medicine, University of Tasmania, Hobart, Australia
| | - Rachel E Neale
- QIMR Berghofer Medical Research Institute and School of Public Health, University of Queensland, Brisbane, Australia
| | - Amanda Neil
- Menzies Research Institute of Tasmania, Hobart, Australia
| | - Savio G Barreto
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Chee Y Ooi
- University of New South Wales, Sydney, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, Australia
| | | | - Jeremy S Wilson
- University of New South Wales, Sydney, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, Australia
| | - Tony Pang
- University of Sydney, Sydney, Australia
| | - Minoti Apte
- University of New South Wales, Sydney, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, Australia
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Ozturk D, Sivaslioglu A, Bulus H, Ozturk B. TyG index is positively associated with HOMA-IR in cholelithiasis patients with insulin resistance: Based on a retrospective observational study. Asian J Surg 2024; 47:2579-2583. [PMID: 38508891 DOI: 10.1016/j.asjsur.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 12/24/2023] [Accepted: 03/01/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND/OBJECTIVE Cholelithiasis is a common disease but pose significant global health and financial burdens. Mechanisms of the disease are associated with insulin resistance (IR), obesity, metabolic syndrome, and type 2 diabetes. Insulin resistance is commonly observed in cholelithiasis patients. More recently, the triglyceride-glucose (TyG) index has been proposed as an alternative marker of insulin resistance. In our study we aimed to understand whether the TyG index is correlated with HOMA-IR in cholelithiasis patients. And also we aimed the predict a cutoff value for determining insulin resistance in cholelithiasis patients. METHODS A total of 184 cholelithiasis patients were matched in terms of age, gender, and BMI. They were divided into two groups based on their Homa IR levels (IR and Non-IR group). This study was a retrospective, observational study and clinical data was obtained from electronic medical records. Cutoff value for Tyg index was established through ROC Analysis. Binary Logistic Regression was used to identify factors affecting insulin resistance. RESULTS A significant cutoff value was found for the TyG index in determining the presence of insulin resistance. Having a TyG index of ≥8.71 indicates the presence of insulin resistance. The sensitivity was 68.48%, the specificity was 58.70%. Binary Logistic Regression analyses showed that an increase in Tyg Index, waist circumference and waist-to-height ratio values increases the risk of insulin resistance by 2.705 (p = 0.001), 1.032 (p = 0.029), and 334.057 (p = 0.012) times respectively. CONCLUSION Our study indicated that TyG index is positively correlated with HOMA-IR. TyG index was found as a risk factor for insulin resistance.
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Affiliation(s)
- Dogan Ozturk
- University of Health Sciences, Ankara Ataturk Sanatoryum Training and Research Hospital, Department of General Surgery, Ankara, Turkiye
| | - Aysegul Sivaslioglu
- Hacettepe University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Ankara, Turkiye.
| | - Hakan Bulus
- University of Health Sciences, Ankara Ataturk Sanatoryum Training and Research Hospital, Department of General Surgery, Ankara, Turkiye
| | - Bulent Ozturk
- University of Health Sciences, Ankara Ataturk Sanatoryum Training and Research Hospital, Department of General Surgery, Ankara, Turkiye
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Zhu R, Lei Y, Wang S, Zhang J, Mengjiao Lv, Jiang R, Zhou J, Li T, Guo L. Plantago consumption significantly reduces total cholesterol and low-density lipoprotein cholesterol in adults: A systematic review and meta-analysis. Nutr Res 2024; 126:123-137. [PMID: 38688104 DOI: 10.1016/j.nutres.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 03/26/2024] [Accepted: 03/26/2024] [Indexed: 05/02/2024]
Abstract
Plantago is rich in soluble fiber, known for its beneficial health effects. Given this, we hypothesized that Plantago consumption might positively influence blood lipid in adults. Researchers have conducted numerous randomized controlled trials (RCTs), revealing the impacts of Plantago consumption on various blood lipid parameters. However, findings regarding specific blood lipid parameters have shown variability. This study aimed to comprehensively assess the effect of Plantago consumption on blood lipid parameters. Eligible studies evaluating the effects of Plantago consumption on blood lipid were searched in 5 electronic databases published up to August 2023. Analysis used a random effects model to determine weighted mean difference and 95% confidence intervals. In total, 29 RCTs including 2769 participants were included. Compared with the control group, Plantago consumption significantly reduced total cholesterol (TC) by 0.28 mmol/L and low-density lipoprotein cholesterol (LDL-C) by 0.35 mmol/L, correlating to an estimated 7% decrease in cardiovascular event risk. Conversely, no substantial effects were observed on high-density lipoprotein cholesterol or triglycerides. Subgroup analyses of 29 RCTs revealed that TC concentrations were significantly lowered in studies that included male participants, those who were healthy, or had lipid disorders. Additionally, TC and LDL-C were significantly lower in participants consuming Plantago husk or psyllium, and soluble fiber intake was specifically effective in lowering TC, LDL-C, and triglycerides. In conclusion, Plantago consumption can significantly lower TC and LDL-C concentrations. The findings will provide crucial insights into the potential of Plantago in dietary strategies for blood lipid management.
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Affiliation(s)
- Ruiting Zhu
- Department of Rehabilitation, School of Nursing, Jilin University, Changchun, Jilin, China, 130021
| | - Yangyang Lei
- Department of Rehabilitation, School of Nursing, Jilin University, Changchun, Jilin, China, 130021
| | - Saikun Wang
- Department of Rehabilitation, School of Nursing, Jilin University, Changchun, Jilin, China, 130021
| | - Jingyi Zhang
- College of Animal Sciences, Jilin University, Changchun, Jilin, China, 130062
| | - Mengjiao Lv
- Department of Rehabilitation, School of Nursing, Jilin University, Changchun, Jilin, China, 130021
| | - Ruixue Jiang
- Department of Rehabilitation, School of Nursing, Jilin University, Changchun, Jilin, China, 130021
| | - Jinjian Zhou
- Department of Rehabilitation, School of Nursing, Jilin University, Changchun, Jilin, China, 130021
| | - Tianshu Li
- College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China, 130021
| | - Lirong Guo
- Department of Rehabilitation, School of Nursing, Jilin University, Changchun, Jilin, China, 130021.
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于 文, 夏 静, 陈 芳, 焦 鹏, 崔 平, 张 弛, 王 宇, 单 雪, 王 新. [Establishment and Validation of a Predictive Model for Gallstone Disease in the General Population: A Multicenter Study]. SICHUAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF SICHUAN UNIVERSITY. MEDICAL SCIENCE EDITION 2024; 55:641-652. [PMID: 38948266 PMCID: PMC11211771 DOI: 10.12182/20240560501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Indexed: 07/02/2024]
Abstract
Objective Gallstone disease (GSD) is one of the common digestive tract diseases with a high worldwide prevalence. The effects of GSD on patients include but are not limited to the symptoms of nausea, vomiting, and biliary colic directly caused by GSD. In addition, there is mounting evidence from cohort studies connecting GSD to other conditions, such as cardiovascular diseases, biliary tract cancer, and colorectal cancer. Early identification of patients at a high risk of GSD may help improve the prevention and control of the disease. A series of studies have attempted to establish prediction models for GSD, but these models could not be fully applied in the general population due to incomplete prediction factors, small sample sizes, and limitations in external validation. It is crucial to design a universally applicable GSD risk prediction model for the general population and to take individualized intervention measures to prevent the occurrence of GSD. This study aims to conduct a multicenter investigation involving more than 90000 people to construct and validate a complete and simplified GSD risk prediction model. Methods A total of 123634 participants were included in the study between January 2015 and December 2020, of whom 43929 were from the First Affiliated Hospital of Chongqing Medical University (Chongqing, China), 11907 were from the First People's Hospital of Jining City (Shandong, China), 1538 were from the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China), and 66260 were from the People's Hospital of Kaizhou District (Chongqing, China). After excluding patients with incomplete clinical medical data, 35976 patients from the First Affiliated Hospital of Chongqing Medical University were divided into a training data set (n=28781, 80%) and a validation data set (n=7195, 20%). Logistic regression analyses were performed to investigate the relevant risk factors of GSD, and a complete risk prediction model was constructed. Factors with high scores, mainly according to the nomograms of the complete model, were retained to simplify the model. In the validation data set, the diagnostic accuracy and clinical performance of these models were validated using the calibration curve, area under the curve (AUC) of the receiver operating characteristic curve, and decision curve analysis (DCA). Moreover, the diagnostic accuracy of these two models was validated in three other hospitals. Finally, we established an online website for using the prediction model (The complete model is accessible at https://wenqianyu.shinyapps.io/Completemodel/, while the simplified model is accessible at https://wenqianyu.shinyapps.io/Simplified/). Results After excluding patients with incomplete clinical medical data, a total of 96426 participants were finally included in this study (35876 from the First Affiliated Hospital of the Chongqing Medical University, 9289 from the First People's Hospital of Jining City, 1522 from the Tianjin Medical University Cancer Institute, and 49639 from the People's Hospital of Kaizhou District). Female sex, advanced age, higher body mass index, fasting plasma glucose, uric acid, total bilirubin, gamma-glutamyl transpeptidase, and fatty liver disease were positively associated with risks for GSD. Furthermore, gallbladder polyps, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and aspartate aminotransferase were negatively correlated to risks for GSD. According to the nomograms of the complete model, a simplified model including sex, age, body mass index, gallbladder polyps, and fatty liver disease was constructed. All the calibration curves exhibited good consistency between the predicted and observed probabilities. In addition, DCA indicated that both the complete model and the simplified model showed better net benefits than treat-all and treat-none. Based on the calibration plots, DCA, and AUCs of the complete model (AUC in the internal validation data set=74.1% [95% CI: 72.9%-75.3%], AUC in Shandong=71.7% [95% CI: 70.6%-72.8%], AUC in Tianjin=75.3% [95% CI: 72.7%-77.9%], and AUC in Kaizhou=72.9% [95% CI: 72.5%-73.3%]) and the simplified model (AUC in the internal validation data set=73.7% [95% CI: 72.5%-75.0%], AUC in Shandong=71.5% [95% CI: 70.4%-72.5%], AUC in Tianjin=75.4% [95% CI: 72.9%-78.0%], and AUC in Kaizhou=72.4% [95% CI: 72.0%-72.8%]), we concluded that the complete and simplified risk prediction models for GSD exhibited excellent performance. Moreover, we detected no significant differences between the performance of the two models (P>0.05). We also established two online websites based on the results of this study for GSD risk prediction. Conclusions This study innovatively used the data from 96426 patients from four hospitals to establish a GSD risk prediction model and to perform risk prediction analyses of internal and external validation data sets in four cohorts. A simplified model of GSD risk prediction, which included the variables of sex, age, body mass index, gallbladder polyps, and fatty liver disease, also exhibited good discrimination and clinical performance. Nonetheless, further studies are needed to explore the role of low-density lipoprotein cholesterol and aspartate aminotransferase in gallstone formation. Although the validation results of the complete model were better than those of the simplified model to a certain extent, the difference was not significant even in large samples. Compared with the complete model, the simplified model uses fewer variables and yields similar prediction and clinical impact. Hence, we recommend the application of the simplified model to improve the efficiency of screening high-risk groups in practice. The use of the simplified model is conducive to enhancing the self-awareness of prevention and control in the general population and early intervention for GSD.
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Affiliation(s)
- 文倩 于
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 静 夏
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 芳圆 陈
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 鹏 焦
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 平 崔
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 弛 张
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 宇 王
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 雪峰 单
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - 新 王
- 四川大学华西公共卫生学院/四川大学华西第四医院 (成都 610041)West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
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Sun Y, Xu C, Luo J, Li S, Chen S, Cen Y, Xu P. Comprehensive analysis of differential long non-coding RNA and messenger RNA expression in cholelithiasis using high-throughput sequencing and bioinformatics. Front Genet 2024; 15:1375019. [PMID: 38808330 PMCID: PMC11130440 DOI: 10.3389/fgene.2024.1375019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/24/2024] [Indexed: 05/30/2024] Open
Abstract
Background The etiology of gallstone disease (GSD) has not been fully elucidated. Consequently, the primary objective of this study was to scrutinize and provisionally authenticate the distinctive expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in GSD. Methods RiboNucleic Acid (RNA) sequencing was used on four paired human gallbladder samples for the purpose of this study. Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified and subjected to analysis of their biological functions. The Pearson's correlation coefficients between DElncRNAs and DEmRNAs were computed to construct a co-expression network delineating their associations. Furthermore, both cis- and trans-regulatory networks of selected lncRNAs were established and visualized. Additionally, a competing endogenous RNA (ceRNA) regulatory network was constructed. To validate the RNA-sequencing data, we performed a Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) on 10 paired human gallbladder samples, assessing the expressions of the top 4 DEmRNAs and DElncRNAs in gallstone and control samples. Results A total of 934 DEmRNAs and 304DElncRNAs were successfully identified. Functional enrichment analysis indicated a predominant involvement in metabolic-related biological functions. Correlation analysis revealed a strong association between the expressions of 597 DEmRNAs and 194 DElncRNAs. Subsequently, both a cis-lncRNA-mRNA and a trans-lncRNA-Transcription Factor (TF)-mRNA regulatory network were meticulously constructed. Additionally, a ceRNA network, comprising of 24 DElncRNAs, 201 DEmRNAs, and 120 predicted miRNAs, was established. Furthermore, using RT-qPCR, we observed significant upregulation of AC004692.4, HECW1-IT1, SFRP4, and COMP, while LINC01564, SLC26A3, RP1-27K12.2, and GSTA2 exhibited marked downregulation in gallstone samples. Importantly, these findings were consistent with the sequencing. Conclusion We conducted a screening process to identify DElncRNAs and DEmRNAs in GSD. This approach contributes to a deeper understanding of the genetic factors involved in the etiology of gallstones.
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Affiliation(s)
- Yanbo Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Conghui Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
- School of Medicine, Yunnan University, Kunming, China
| | - Jing Luo
- Department of Gastrointestinal Surgery, Qujing No. 1 People’s Hospital, Qujing, Yunnan, China
| | - Shumin Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shi Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yunyun Cen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Pengyuan Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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Luo Y, Gao X, Xiao M, Yang F, Zhu X, Qiao G, Xiang C, Tao J. Association between dietary inflammatory index and gallstones in US adults. Front Nutr 2024; 11:1403438. [PMID: 38765815 PMCID: PMC11099284 DOI: 10.3389/fnut.2024.1403438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 04/24/2024] [Indexed: 05/22/2024] Open
Abstract
Introduction Previous studies have found that diet's inflammatory potential is related to various diseases. However, little is known about its relationship with gallstones. The present study aims to investigate the relationship between dietary inflammatory index (DII) and gallstones. Methods Data were obtained from the 2003-2020 National Health and Nutrition Examination Survey (NHANES). We used the nearest neighbor propensity score matching (PSM) with a ratio of 1:1 to reduce selection bias. Logistic regression models estimated the association between DII and gallstones. The non-linear relationship was explored with restricted cubic splines (RCS). BMI subgroup stratification was performed to explore further the connection between DII and gallstones in different populations. Results 10,779 participants were included. Before and after PSM, gallstone group individuals had higher DII scores than non-gallstone group individuals (p < 0.05). Matched logistic regression analysis showed that DII scores were positively correlated with gallstone risk (adjusted OR = 1.14, 95% CI 1.01, 1.29). The stratified analysis showed that this association was stronger in overweight or obese people (adjusted OR = 1.18, 95% CI 1.03, 1.34). RCS analysis suggested that DII and gallstones showed a "J"-shaped non-linear dose-response relationship (p non-linear <0.001). Conclusion Higher DII score is positively associated with the risk of gallstones, particularly in overweight or obese population, and this relationship is a "J"-shaped non-linear relationship. These results further support that avoiding or reducing a pro-inflammatory diet can be an intervention strategy for gallstone management, particularly in the overweight or obese population.
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Affiliation(s)
- Yanling Luo
- School of Nursing, Hubei University of Chinese Medicine, Wuhan, China
| | - Xiaolian Gao
- School of Nursing, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
| | - Mingzhong Xiao
- Department of Hepatology, Hubei Key Laboratory of The Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
- Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Fen Yang
- School of Nursing, Hubei University of Chinese Medicine, Wuhan, China
| | - Xinhong Zhu
- School of Nursing, Hubei University of Chinese Medicine, Wuhan, China
| | - Guiyuan Qiao
- School of Nursing, Hubei University of Chinese Medicine, Wuhan, China
| | - Cong Xiang
- School of Nursing, Hubei University of Chinese Medicine, Wuhan, China
| | - Junxiu Tao
- Department of Hepatology, Hubei Key Laboratory of The Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
- Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
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Zhou Y, Chen ZQ. Research on the prognostic value of adjusting intraperitoneal three-dimensional quality evaluation mode in laparoscopic cholecystectomy patients. World J Gastrointest Surg 2024; 16:1078-1086. [PMID: 38690039 PMCID: PMC11056672 DOI: 10.4240/wjgs.v16.i4.1078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/30/2024] [Accepted: 03/15/2024] [Indexed: 04/22/2024] Open
Abstract
BACKGROUND Benign gallbladder diseases have become a high-prevalence condition not only in China but also worldwide. The main types of benign gallbladder diseases include gallbladder polyps, acute and chronic cholecystitis, and gallstones, with gallstones being the most common, accounting for over 70% of cases. Although the mortality rate of benign gallbladder diseases is low, they carry obvious potential risks. Studies have shown that an increased incidence of benign gallbladder diseases can increase the risk of cardiovascular diseases and gallbladder cancer, resulting in a substantial disease burden on patients and their families. AIM To assess the medical utility of the Configuration-Procedure-Consequence (CPC) three-dimensional quality evaluation model in modulating the prognosis of laparoscopic cholecystectomy patients. METHODS A total of 98 patients who underwent laparoscopic cholecystectomy in our hospital from February 2020 to January 2022 were selected as the subjects. According to the random number table method, they were divided into a study group and a control group, with 49 patients in each group. The control group received routine perioperative care, while the study group had the addition of the CPC three-dimensional quality evaluation. The postoperative recovery-related indicators (time to first flatus, time to oral intake, time to ambulation, hospital stay), stress indicators (cortisol and adrenaline levels), distinctions in anxiety and depression status, and the incidence of perioperative complications were compared. RESULTS The time to first flatus, time to oral intake, time to ambulation, and hospital stay of the study group patients were obviously lower than those of the control group patients, with statistical significance (P < 0.05). On the 1st day after admission, there were no obvious distinctions in cortisol and adrenaline levels in blood samples, as well as in the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores between the study group and the control group (P > 0.05). However, on the 3rd day after surgery, the cortisol and adrenaline levels, as well as SAS and SDS scores of the study group patients, were obviously lower than those of the control group patients (P < 0.05). The study group had 2 cases of incisional infection and 1 case of pulmonary infection, with a total incidence of complications of 6.12% (3/49), which was obviously lower than the 20.41% (10/49) in the control group (P < 0.05). CONCLUSION Implementing the CPC three-dimensional quality evaluation model for patients undergoing laparoscopic cholecystectomy can help accelerate their perioperative recovery process, alleviate perioperative stress symptoms, mitigate anxiety, depression, and other adverse emotions, and to some extent, reduce the incidence of perioperative complications.
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Affiliation(s)
- Yuan Zhou
- Operating Room, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang 222000, Jiangsu Province, China
| | - Zhan-Qing Chen
- Operating Room, The Second People's Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang 222000, Jiangsu Province, China
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Costa CJ, Nguyen MTT, Vaziri H, Wu GY. Genetics of Gallstone Disease and Their Clinical Significance: A Narrative Review. J Clin Transl Hepatol 2024; 12:316-326. [PMID: 38426197 PMCID: PMC10899874 DOI: 10.14218/jcth.2023.00563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/16/2024] [Accepted: 01/29/2024] [Indexed: 03/02/2024] Open
Abstract
Gallstone (GS) disease is common and arises from a combination of genetic and environmental factors. Although genetic abnormalities specifically leading to cholesterol GSs are rare, there are clinically significant gene variants associated with cholesterol GSs. In contrast, most bilirubin GSs can be attributed to genetic defects. The pathogenesis of cholesterol and bilirubin GSs differs greatly. Cholesterol GSs are notably influenced by genetic variants within the ABC protein superfamily, including ABCG8, ABCG5, ABCB4, and ABCB11, as well as genes from the apolipoprotein family such as ApoB100 and ApoE (especially the E3/E3 and E3/E4 variants), and members of the MUC family. Conversely, bilirubin GSs are associated with genetic variants in highly expressed hepatic genes, notably UGT1A1, ABCC2 (MRP2), ABCC3 (MRP3), CFTR, and MUC, alongside genetic defects linked to hemolytic anemias and conditions impacting erythropoiesis. While genetic cases constitute a small portion of GS disease, recognizing genetic predisposition is essential for proper diagnosis, treatment, and genetic counseling.
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Affiliation(s)
- Christopher J. Costa
- Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Minh Thu T. Nguyen
- Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Haleh Vaziri
- Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - George Y. Wu
- Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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Obaid AM, Turki A, Bellaaj H, Ksantini M. Diagnosis of Gallbladder Disease Using Artificial Intelligence: A Comparative Study. INT J COMPUT INT SYS 2024; 17:46. [DOI: 10.1007/s44196-024-00431-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 02/05/2024] [Indexed: 01/05/2025] Open
Abstract
AbstractGallbladder (GB) disease is a common pathology that needs correct and early diagnosis for the optimum medical treatment. Early diagnosis is crucial as any delay or misdiagnosis can worsen the patient situation. Incorrect diagnosis could also lead to an escalation in patient symptoms and poorer clinical outcomes. The use of Artificial Intelligence (AI) techniques, ranging from Machine Learning (ML) to Deep Learning (DL) to predict disease progression, identify abnormalities, and estimate mortality rates associated with GB disorders has increased over the past decade. To this end, this paper provides a comprehensive overview of the AI approaches used in the diagnosis of GB illnesses. This review compiles and compares relevant papers from the last decade to show how AI might enhance diagnostic precision, speed, and efficiency. Therefore, this survey gives researchers the opportunity to find out both the diagnosis of GB diseases and AI techniques in one place. The maximum accuracy rate by ML was when using SVM with 96.67%, whilst the maximum accuracy rate by DL was by utilising a unique structure of VGG, GoogleNet, ResNet, AlexNet and Inception with 98.77%. This could provide a clear path for further investigations and algorithm’s development to boost diagnostic results to improve the patient’s condition and choose the appropriate treatment.
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Esen İ, Arslan H, Aktürk Esen S, Gülşen M, Kültekin N, Özdemir O. Early prediction of gallstone disease with a machine learning-based method from bioimpedance and laboratory data. Medicine (Baltimore) 2024; 103:e37258. [PMID: 38394521 PMCID: PMC11309733 DOI: 10.1097/md.0000000000037258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 01/23/2024] [Indexed: 02/25/2024] Open
Abstract
Gallstone disease (GD) is a common gastrointestinal disease. Although traditional diagnostic techniques, such as ultrasonography, CT, and MRI, detect gallstones, they have some limitations, including high cost and potential inaccuracies in certain populations. This study proposes a machine learning-based prediction model for gallstone disease using bioimpedance and laboratory data. A dataset of 319 samples, comprising161 gallstone patients and 158 healthy controls, was curated. The dataset comprised 38 attributes of the participants, including age, weight, height, blood test results, and bioimpedance data, and it contributed to the literature on gallstones as a new dataset. State-of-the-art machine learning techniques were performed on the dataset to detect gallstones. The experimental results showed that vitamin D, C-reactive protein (CRP) level, total body water, and lean mass are crucial features, and the gradient boosting technique achieved the highest accuracy (85.42%) in predicting gallstones. The proposed technique offers a viable alternative to conventional imaging techniques for early prediction of gallstone disease.
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Affiliation(s)
- İrfan Esen
- Yüksek İhtisas University, Faculty of Medicine Department of Internal Medicine, Ankara, Turkey
| | - Hilal Arslan
- Ankara Yildirim Beyazit University, Department of Software Engineering, Faculty of Engineering and Natural Sciences, Ankara, Turkey
| | | | - Mervenur Gülşen
- Keçiören VM Medicalpark Hospital, Department of Nutrition and Dietetics, Ankara, Turkey
| | - Nimet Kültekin
- Keçiören VM Medicalpark Hospital, Department of Nutrition and Dietetics, Ankara, Turkey
| | - Oğuzhan Özdemir
- Yüksek İhtisas University, Faculty of Medicine Department of Department of Radiology, Ankara, Turkey
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Loveland M, Le Cam E, Ibrahim R, Paulo Ferreira J. Health insurance prevalence and acute pancreatitis mortality: a cross-sectional analysis. J Investig Med 2024; 72:178-180. [PMID: 37674260 DOI: 10.1177/10815589231201328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/08/2023]
Affiliation(s)
- Macklin Loveland
- Department of Medicine, Banner University Medical Center, University of Arizona, Tucson, AZ, USA
| | - Elise Le Cam
- Department of Medicine, Banner University Medical Center, University of Arizona, Tucson, AZ, USA
| | - Ramzi Ibrahim
- Department of Medicine, Banner University Medical Center, University of Arizona, Tucson, AZ, USA
| | - João Paulo Ferreira
- Department of Medicine, Banner University Medical Center, University of Arizona, Tucson, AZ, USA
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Wang D, Ye A, Jiang N. The role of bacteria in gallstone formation. Folia Microbiol (Praha) 2024; 69:33-40. [PMID: 38252338 DOI: 10.1007/s12223-024-01131-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 12/27/2023] [Indexed: 01/23/2024]
Abstract
Gallstones are a prevalent biliary system disorder that is particularly common in women. They can lead to various complications, such as biliary colic, infection, cholecystitis, and even gallbladder cancer. However, the etiology of gallstones remains incompletely understood. The significant role of bacteria in gallstone formation has been demonstrated in recent studies. Certain bacteria not only influence bile composition and the gallbladder environment but also actively participate in stone formation by producing enzymes such as β-glucuronidase and mucus. Therefore, this review aimed to analyze the mechanisms involving the types and quantities of bacteria involved in gallstone formation, providing valuable references for understanding the etiology and clinical treatment of gallstones.
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Affiliation(s)
- Danfeng Wang
- Health Management (Physical Examination) Section of Hubei Third People's Hospital Affiliated to Jianghan University, Wuhan, 430034, People's Republic of China
| | - Aihui Ye
- Wuchang District Shouyilu Street Community Health Service Center, Wuhan, 430061, People's Republic of China
| | - Ni Jiang
- Health Management (Physical Examination) Section of Hubei Third People's Hospital Affiliated to Jianghan University, Wuhan, 430034, People's Republic of China.
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Huang D, Shen S, Zhuang Q, Ye X, Qian Y, Dong Z, Wan X. Ganoderma lucidum polysaccharide ameliorates cholesterol gallstone formation by modulating cholesterol and bile acid metabolism in an FXR-dependent manner. Chin Med 2024; 19:16. [PMID: 38268006 PMCID: PMC10809463 DOI: 10.1186/s13020-024-00889-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 01/18/2024] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Cholesterol gallstone (CG) disease is a worldwide common disease characterized by cholesterol supersaturation in gallbladder bile. Ganoderma lucidum polysaccharide (GLP) has been shown to possess various beneficial effects against metabolic disorders. However, the role and underlying mechanism of GLP in CG formation are still unknown. This study aimed to determine the role of GLP in ameliorating lithogenic diet (LD)-induced CG formation. METHODS Mice were fed either a normal chow diet, a LD, or LD supplemented with GLP. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of genes involved in cholesterol and bile acid (BA) metabolism. The BA concentrations in the ileum were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The microbiota in cecal contents were characterized using 16S ribosomal RNA (16S rRNA) gene sequencing. RESULTS GLP effectively alleviated CG formation induced by LD. Specifically, GLP reduced the total cholesterol (TC) levels, increased the total BA levels, and decreased the cholesterol saturation index (CSI) in gallbladder bile. The protective effect of GLP was attributed to the inhibition of farnesoid X receptor (FXR) signaling, increased hepatic BA synthesis and decreased hepatic cholesterol synthesis and secretion. GLP also altered the BA composition in the ileum, reducing FXR-agonistic BAs and increasing FXR-antagonistic BAs, which may contribute to the inhibition of intestinal FXR signaling. Additionally, GLP improved dysbiosis of the intestinal flora and reduced the serum levels of hydrogen sulfide (H2S), a bacterial metabolite that can induce hepatic FXR, thereby inhibiting hepatic FXR signaling. Moreover, the protective effect of GLP against CG formation could be reversed by both the global and gut-restricted FXR agonists. CONCLUSIONS Taken together, GLP ameliorates CG formation by regulating cholesterol and BA metabolism in an FXR-dependent manner. Our study demonstrates that GLP may be a potential strategy for the prevention against CG disease.
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Affiliation(s)
- Dan Huang
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Shuang Shen
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Qian Zhuang
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Xin Ye
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Yueqin Qian
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
| | - Zhixia Dong
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China.
| | - Xinjian Wan
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China.
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Han F, Zhao T, Zhang Y, Yun Y, Xu Y, Guo S, Zhong Y, Xie X, Shen J. Discovery and exploration of novel somatostatin receptor subtype 5 (SSTR5) antagonists for the treatment of cholesterol gallstones. Eur J Med Chem 2024; 264:116017. [PMID: 38070432 DOI: 10.1016/j.ejmech.2023.116017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/27/2023] [Accepted: 11/28/2023] [Indexed: 12/30/2023]
Abstract
The shortage of cholesterol gallstones treatment intensifies the need to discover of effective small molecule drugs. Clinical follow-up and studies have found that activation of somatostatin receptor subtype 5 (SSTR5) reduce gallbladder contraction and thus increase the risk of cholesterol gallstones, implying that antagonizing SSTR5 may promote gallbladder emptying and reduce the formation of gallstones. Herein, we discovered novel SSTR5 antagonists and firstly investigated its effects on cholesterol gallstone. From loperamide, a reported seed structure with micromole activity, we identified optimal compound 23 as an SSTR5 antagonist exhibiting single-digit nanomolar potency, low hERG inhibition and oral availability. Further in vivo evaluation revealed that 23 significantly promoted gallbladder emptying. Moreover, in a mouse cholesterol gallstone model, 23 (3 mg/kg) effectively reduced the cholesterol gallstones formation, showing better efficacy than the clinical first-line drug UDCA (60 mg/kg), providing a new insight into the development of anti-gallstone drugs.
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Affiliation(s)
- Fanghui Han
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China
| | - Tingting Zhao
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China
| | - Yanglong Zhang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China
| | - Ying Yun
- School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China
| | - Yuanyuan Xu
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China
| | - Shimeng Guo
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
| | - Yongqing Zhong
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; School of Pharmacy, Nanchang University, Nanchang, 330000, Jiangxi Province, China
| | - Xin Xie
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, 264117, China.
| | - Jianhua Shen
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
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Chatterjee A, Irani R. Molecular aspect of gallstone formation: a systematic review. GALLSTONE FORMATION, DIAGNOSIS, TREATMENT AND PREVENTION 2024:71-82. [DOI: 10.1016/b978-0-443-16098-1.00010-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Peng T, Zhou C, Zhang Z, Liu Y, Lin X, Ye Y, Zhong Y, Wang P, Jia Y. Review on bile dynamics and microfluidic-based component detection: Advancing the understanding of bilestone pathogenesis in the biliary tract. BIOMICROFLUIDICS 2024; 18:014105. [PMID: 38370511 PMCID: PMC10869170 DOI: 10.1063/5.0186602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 01/19/2024] [Indexed: 02/20/2024]
Abstract
Bilestones are solid masses found in the gallbladder or biliary tract, which block the normal bile flow and eventually result in severe life-threatening complications. Studies have shown that bilestone formation may be related to bile flow dynamics and the concentration level of bile components. The bile flow dynamics in the biliary tract play a critical role in disclosing the mechanism of bile stasis and transportation. The concentration of bile composition is closely associated with processes such as nucleation and crystallization. Recently, microfluidic-based biosensors have been favored for multiple advantages over traditional benchtop detection assays for their less sample consumption, portability, low cost, and high sensitivity for real-time detection. Here, we reviewed the developments in bile dynamics study and microfluidics-based bile component detection methods. These studies may provide valuable insights into the bilestone formation mechanisms and better treatment, alongside our opinions on the future development of in vitro lithotriptic drug screening of bilestones and bile characterization tests.
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Affiliation(s)
- Tao Peng
- Zhuhai UM Science & Technology Research Institute, Zhuhai, China
| | - Chenxiao Zhou
- Li Po Chun United World College of Hong Kong, Hong Kong, China
| | | | | | - Xiaodong Lin
- Zhuhai UM Science & Technology Research Institute, Zhuhai, China
| | - Yongqing Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yunlong Zhong
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Ping Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yanwei Jia
- Authors to whom correspondence should be addressed: and
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Shukla R, Chadha M, Shekh R, Tiwari RK. Role of probiotics in gallstone treatment. GALLSTONE FORMATION, DIAGNOSIS, TREATMENT AND PREVENTION 2024:169-187. [DOI: 10.1016/b978-0-443-16098-1.00006-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Yuk JS, Park JY. Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study. PLoS One 2023; 18:e0294356. [PMID: 38048308 PMCID: PMC10695378 DOI: 10.1371/journal.pone.0294356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 10/30/2023] [Indexed: 12/06/2023] Open
Abstract
OBJECTIVE To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer. DESIGN A retrospective cohort study. PATIENTS OR OTHER PARTICIPANTS Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019. INTERVENTIONS Participants were divided into MHT and non-MHT groups; the MHT group was analyzed in detail by dividing participants into tibolone, combined estrogen plus progestin by the manufacturer (CEPM) or physician (CEPP), oral estrogen alone, and topical estrogen subgroups. MAIN OUTCOME MEASURES The incidence of gallstones and gallbladder cancer was compared between the two groups. RESULTS This study enrolled 1,004,034 and 381,711 patients in the non-MHT and the MHT groups, respectively. The incidence of gallstones was 2.6% in the non-MHT group and 3.4%, 2.6%, 3.4%, 3.2%, and 4.4% in the tibolone, CEPM, oral estrogen alone, CEPP, and topical estrogen groups, respectively. Cox proportional hazard analysis revealed that all hormones increased the risk of gallstones ([tibolone] hazard ratio [HR]: 1.347, 95% confidence interval [CI]: 1.309-1.387, [CEPM] HR: 1.146, 95% CI: 1.1-1.19, [oral estrogen alone] HR: 1.241, 95% CI: 1.18-1.305, [CEPP] HR: 1.164, 95% CI: 1.01-1.341, [topical estrogen] HR: 1.602, 95% CI: 1.295-1.983). However, the risk of gallbladder cancer did not change with any hormone therapy. CONCLUSIONS All types of MHT including tibolone, increased the risk of gallstones. This risk was the highest with topical estrogen, which may be a result of selection bias due to concerns regarding the adverse effects of CEE and MPA.
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Affiliation(s)
- Jin-Sung Yuk
- Department of Obstetrics and Gynecology, Sanggye Paik Hospital, School of Medicine, Inje University, Seoul, Republic of Korea
| | - Ji Young Park
- Department of Internal Medicine, Sanggye Paik Hospital, School of Medicine, Inje University, Seoul, Republic of Korea
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Yang XT, Wang J, Jiang YH, Zhang L, Du L, Li J, Liu F. Insight into the mechanism of gallstone disease by proteomic and metaproteomic characterization of human bile. Front Microbiol 2023; 14:1276951. [PMID: 38111640 PMCID: PMC10726133 DOI: 10.3389/fmicb.2023.1276951] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 11/16/2023] [Indexed: 12/20/2023] Open
Abstract
Introduction Cholesterol gallstone disease is a prevalent condition that has a significant economic impact. However, the role of the bile microbiome in its development and the host's responses to it remain poorly understood. Methods In this study, we conducted a comprehensive analysis of microbial and human bile proteins in 40 individuals with either gallstone disease or gallbladder polyps. We employed a combined proteomic and metaproteomic approach, as well as meta-taxonomic analysis, functional pathway enrichment, and Western blot analyses. Results Our metaproteomic analysis, utilizing the lowest common ancestor algorithm, identified 158 microbial taxa in the bile samples. We discovered microbial taxa that may contribute to gallstone formation, including β-glucuronidase-producing bacteria such as Streptococcus, Staphylococcus, and Clostridium, as well as those involved in biofilm formation like Helicobacter, Cyanobacteria, Pseudomonas, Escherichia coli, and Clostridium. Furthermore, we identified 2,749 human proteins and 87 microbial proteins with a protein false discovery rate (FDR) of 1% and at least 2 distinct peptides. Among these proteins, we found microbial proteins crucial to biofilm formation, such as QDR3, ompA, ndk, pstS, nanA, pfIB, and dnaK. Notably, QDR3 showed a gradual upregulation from chronic to acute cholesterol gallstone disease when compared to polyp samples. Additionally, we discovered other microbial proteins that enhance bacterial virulence and gallstone formation by counteracting host oxidative stress, including sodB, katG, rbr, htrA, and ahpC. We also identified microbial proteins like lepA, rtxA, pckA, tuf, and tpiA that are linked to bacterial virulence and potential gallstone formation, with lepA being upregulated in gallstone bile compared to polyp bile. Furthermore, our analysis of the host proteome in gallstone bile revealed enhanced inflammatory molecular profiles, including innate immune molecules against microbial infections. Gallstone bile exhibited overrepresented pathways related to blood coagulation, folate metabolism, and the IL-17 pathway. However, we observed suppressed metabolic activities, particularly catabolic metabolism and transport activities, in gallstone bile compared to polyp bile. Notably, acute cholelithiasis bile demonstrated significantly impaired metabolic activities compared to chronic cholelithiasis bile. Conclusion Our study provides a comprehensive metaproteomic analysis of bile samples related to gallstone disease, offering new insights into the microbiome-host interaction and gallstone formation mechanism.
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Affiliation(s)
- Xue-Ting Yang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Jie Wang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Ying-Hua Jiang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Lei Zhang
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
| | - Ling Du
- Key Laboratory of Digestive Cancer Full Cycle Monitoring and Precise Intervention of Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, Shanghai, China
| | - Jun Li
- Department of Surgery, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Feng Liu
- Minhang Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, Shanghai, China
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