• Acute Pancreatitis
• Acute kidney injury
• LASSO regression
• MIMIC-IV database
• Nomogram

• Humans
• Acute Disease
• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/epidemiology
• Intensive Care Units
• Pancreatitis/diagnosis
• Retrospective Studies
• Risk Assessment

• NIR-remotely triggered
• adjustable activity behavior
• controlled sterilization
• hyperthermia
• modified spores
• transitive nanoheaters

Bile acids (BAs) are amphiphilic molecules with 24 carbon atoms and consist of a hydrophobic and a rigid steroid nucleus, to which are attached a hydrophilic hydroxyl group and a flexible acidic aliphatic side chain. The steroidal core of BAs constitutes a saturated cyclopentanoperhydrophenanthrene skeleton, consisting of three six-membered (A, B, and C) and one five-membered ring (D). Primary BAs are produced in the hepatocytes, while secondary BAs are formed by modifying the primary BAs in the intestinal lumen, i.e., by the reactions of 7α-dehydroxylation and deconjugation of cholic acid (CA) and chenodeoxycholic acid (CDCA). The most important secondary BAs are deoxycholic acid (DCA) and lithocholic acid (LCA). The BAs realize their effects through nuclear farnesoid X receptors (FXRs) and membrane TGR5 receptors. It has been found that BAs are also associated with other receptors such as the vitamin D receptor (VDR), from which the most significant ligand is calcitriol, as well as with pregnane X receptor (PXR) and potentially with the constitutive androstane receptor (CAR), whose ligands are numerous, structurally different xenobiotics that show greater affinity to BAs. The BAs as therapeutic agents (drugs) have the potential to produce beneficial effects in cases of sexually transmitted diseases, primary biliary cirrhosis (PBC), primary sclerosing cholangitis, gallstones, digestive tract diseases, cystic fibrosis, and cancer. Ursodeoxycholic acid (UDCA) was the only drug approved by the US Food and Drug Administration (FDA) for the treatment of PBC. In this paper, the different pathways of bile acid biosynthesis are explained as well as chemical modifications and the synthesis of different keto derivatives of BAs. Also, the effects of BAs on digestion of nutrients, their role as drugs, and, in particular, the emphasis on the hypoglycemic properties of 7α, 12α-dihydroxy−12–keto−5β-cholanic acid in the treatment of diabetes mellitus are examined in detail.

• BAs
• biosynthesis of BAs
• chemical modification
• chemical synthesis
• drugs

• Metformin
• diabetes
• glucotoxicity
• heart failure
• lipotoxicity

• Animals
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• Glycation End Products, Advanced/metabolism
• Heart Failure/drug therapy
• Heart Failure/metabolism
• Humans
• Hypoglycemic Agents/therapeutic use
• Metformin/therapeutic use

Notoginseng (Sanqi), the roots and rhizomes of Panax notoginseng and safflower, the flowers of Carthamus tinctorius, are widely used traditional Chinese medicines (TCMs) for the treatment of cardiovascular diseases. Positive evidences have fueled growing acceptance for cardioprotective effects of the combination of the notoginseng total saponins and safflower total flavonoids (CNS) against myocardial ischemia (MI). However, the underlying cardioprotective mechanisms of CNS are still obscured. Metabolomics is a comprehensive tool for investigating biological mechanisms of disease, monitoring therapeutic outcomes, and advancing drug discovery and development. Herein, we investigated the cardioprotective effects of CNS on the isoproterenol (ISO)-induced MI rats by using plasma and urine metabolomics based on ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) and multiple pharmacodynamics approaches. The results showed that pretreatment with CNS could attenuate the cardiac injury resulting from ISO, as evidenced by decreasing the myocardial infarct size, converting the echocardiographic, histopathological, and plasma biochemical abnormalities, and reversing the perturbations of plasma and urine metabolic profiles, particularly for the 55.0 mg/kg dosage group. In addition, 44 metabolites were identified as the potential MI biomarkers, mainly including a range of free fatty acids (FFAs), sphingolipids, and glycerophospholipids. CNS pretreatment group may robustly ameliorate these potential MI-related biomarkers. The accumulation of LysoPCs and FFAs, caused by PLA₂, may activate NF-κB pathway and increase proinflammatory cytokines. However, our results showed that CNS at 55.0 mg/kg dosage could maximally attenuate the NF-κB signaling pathway, depress the expressions of TNF-α, IL-6, IL-1β, and PLA₂. The results suggested that the anti-inflammatory property of CNS may contribute to its cardioprotection against MI. Our results demonstrate that the integrating of metabolomics with pharmacodynamics provides a reasonable approach for understanding the therapeutic effects of TCMs and CNS provide a potential candidate for prevention and treatment of MI.

• UPLC-Q-TOF/MS
• cardioprotective effects
• metabolomics
• myocardial ischemia
• notoginseng total saponins
• safflower total flavonoids

非酒精性脂肪性肝炎(non-alcoholic steatohepatitis, NASH)是非酒精性脂肪肝病的进展形式, 可能会进展为肝硬化或肝细胞性肝癌. 单纯的节食及生活方式改变难以坚持, 且无法减缓疾病进展. 传统治疗方法对脂肪变性和炎症有效, 但其对纤维化无效, 而纤维化恰巧是判断患者预后的一种重要标准. 随着对NASH发病机制和进展了解的不断深入, 目前正在进行的研究评估了一些前景良好的、靶向治疗, 同时可逆转纤维化的新型治疗方法, 这些均使得未来NASH治疗前景更加乐观.

• 非酒精性脂肪肝病
• 非酒精性脂肪性肝炎
• 治疗
• 法尼酯X受体
• 胰高血糖素样肽-1
• 活性氧

Congenital heart defects (CHDs) affect approximately 1% of live births and are a major source of childhood morbidity and mortality even in countries with advanced healthcare systems. Along with phenotypic heterogeneity, the underlying etiology of CHDs is multifactorial, involving genetic, epigenetic, and/or environmental contributors. Clear dissection of the underlying mechanism is a powerful step to establish individualized therapies. However, the majority of CHDs are yet to be clearly diagnosed for the underlying genetic and environmental factors, and even less with effective therapies. Although the survival rate for CHDs is steadily improving, there is still a significant unmet need for refining diagnostic precision and establishing targeted therapies to optimize life quality and to minimize future complications. In particular, proper identification of disease associated genetic variants in humans has been challenging, and this greatly impedes our ability to delineate gene–environment interactions that contribute to the pathogenesis of CHDs. Implementing a systematic multileveled approach can establish a continuum from phenotypic characterization in the clinic to molecular dissection using combined next-generation sequencing platforms and validation studies in suitable models at the bench. Key elements necessary to advance the field are: first, proper delineation of the phenotypic spectrum of CHDs; second, defining the molecular genotype/phenotype by combining whole-exome sequencing and transcriptome analysis; third, integration of phenotypic, genotypic, and molecular datasets to identify molecular network contributing to CHDs; fourth, generation of relevant disease models and multileveled experimental investigations. In order to achieve all these goals, access to high-quality biological specimens from well-defined patient cohorts is a crucial step. Therefore, establishing a CHD BioCore is an essential infrastructure and a critical step on the path toward precision child health cardiovascular medicine.

• RNA-sequencing
• bio banking
• congenital heart defects
• repository
• transcriptome
• variants
• whole-exome sequencing

AIM: To compare lymph node dissection results of minimally invasive esophagectomy (MIE) and open surgery for esophageal squamous cell carcinoma.

METHODS: We retrospectively reviewed data from patients who underwent MIE or open surgery for esophageal squamous cell carcinoma from January 2011 to September 2014. Number of lymph nodes resected, positive lymph node (pN+) rate, lymph node sampling (LNS) rate and lymph node metastatic (LNM) rate were evaluated.

RESULTS: Among 447 patients included, 123 underwent MIE and 324 underwent open surgery. The number of lymph nodes resected did not significantly differ between the MIE and open surgery groups (21.1 ± 4.3 vs 20.4 ± 3.8, respectively, P = 0.0944). The pN+ rate of stage T3 esophageal squamous cell carcinoma in the open surgery group was higher than that in the MIE group (16.3% vs 11.4%, P = 0.031), but no differences was observed for stages T1 and T2 esophageal squamous cell carcinoma. The LNS rate at left para-recurrent laryngeal nerve (RLN) site was significantly higher for open surgery than for MIE (80.2% vs 43.9%, P < 0.001), but no differences were noted at other sites. The LNM rate at left para-RLN site in the open surgery group was significantly higher than that in the MIE group, regardless of pathologic T stage.

CONCLUSION: For stages T1 and T2 esophageal squamous cell carcinoma, the lymph node dissection result after MIE was comparable to that achieved by open surgery. However, the efficacy of MIE in lymphadenectomy for stage T3 esophageal squamous cell carcinoma, particularly at left para-RLN site, remains to be improved.

• Esophageal cancer
• Lymph node
• Minimally invasive
• Surgery

• Aged
• Carcinoma, Squamous Cell/pathology
• Carcinoma, Squamous Cell/surgery
• China
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Esophageal Squamous Cell Carcinoma
• Esophagectomy/methods
• Female
• Humans
• Laparoscopy
• Lymph Node Excision/methods
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Recurrent Laryngeal Nerve Injuries/etiology
• Retrospective Studies
• Risk Factors
• Treatment Outcome

The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors.

• DNA repair
• HSP90 inhibitor ganetespib
• apoptosis
• cell cycle
• ionizing radiation
• lung adenocarcinoma
• senescence
• xenografted tumors

• P30 CA047904 NCI NIH HHS
• P50 CA090440 NCI NIH HHS
• R21 CA164740 NCI NIH HHS