Hyperuricemia is associated with higher all-cause and cardiovascular mortality. However, the role of social determinants of health (SDoH) in this context remains unclear. This study aims to examine the relationship between SDoH, hyperuricemia, all-cause and cardiovascular mortality, and explore the mediating role of SDoH in these relationships.

This cohort study analyzed data from 23,919 US adults (aged ≥ 20) in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016, with linked mortality data through December 31, 2019. Two primary exposures were examined: hyperuricemia, defined as serum uric acid level > 420 µmol/L in males and > 360 µmol/L in females, and SDoH, which encompassed education level, marital status, income-to-poverty ratio (PIR), food security, health insurance, regular health-care access, housing instability, and employment. The primary outcomes were all-cause and cardiovascular mortality. Statistical methods included logistic regression, Cox proportional hazard model, and mediation analysis.

The study cohort had a mean (SD) age of 49.27 (17.63) years, with 48.28% (95%Cl, 47.69%-48.86%) being male, and 68.52% (95%Cl, 65.27%-71.60%) identified as non-Hispanic White. Having three or more unfavorable SDoH significantly mediated the link between hyperuricemia and both all-cause and cardiovascular mortality. SDoH ≥ 6, SDoH = 5, SDoH = 4, and SDoH = 3 mediated 20.30% (P = 0.004), 13.94% (P = 0.044), 23.59% (P = 0.018), and 13.88% (P = 0.008) of the association between hyperuricemia and all-cause mortality, respectively. SDoH ≥ 6, SDoH = 5, SDoH = 4, and SDoH = 3 mediated 15.35% (P = 0.006), 14.87% (P = 0.050), 20.68% (P = 0.026), and 9.45% (P = 0.012) of the association between hyperuricemia and cardiovascular mortality.

SDoH significantly mediated the relationship between hyperuricemia and both all-cause and cardiovascular mortality.

Pegloticase rapidly reduces serum urate (SU) in uncontrolled gout. This preliminary retrospective analysis of a large US rheumatology database examined post-pegloticase use and SU-lowering efficacy of oral urate-lowering therapy (ULT; allopurinol, febuxostat, probenecid).

Patients in the United Rheumatology (UR)-NICE data repository with first pegloticase code (J2507) in 2012-2022 and data for ≥ 60 days following last infusion were included. Post-pegloticase oral ULT efficacy was defined as SU < 6 mg/dL after oral ULT initiation and examined by shorter (< 12 infusions) and longer (≥ 12 infusions) pegloticase course and by time to post-pegloticase oral ULT start.

A total of 211 patients (77.3% male; 62.7 ± 12.8 years, body mass index 32.9 ± 7.2 kg/m2, estimated glomerular filtration rate 66.0 ± 24.7 ml/min/1.73 m2) with gout [74.4% tophaceous, SU 7.9 ± 2.5 mg/dL (n = 148)] were included; 66.8% received pre-pegloticase oral ULT (48.8% allopurinol, 32.2% febuxostat, and/or 12.3% probenecid). Patients received 12.3 ± 12.6 pegloticase infusions [median 9; 88 (42%) ≥ 12 infusions; 2.3 ± 2.0 weeks between infusions], with 115 patients (54.5%) beginning oral ULT after pegloticase discontinuation (67.0% allopurinol, 43.5% febuxostat, and/or 16.5% probenecid) most-often (66.1%) ≤ 30 days of last infusion. More patients who received ≥ 12 infusions than < 12 infusions had SU < 6 mg/dL with post-pegloticase oral ULT use [first post-ULT SU < 6 mg/dL, 78.4% vs. 36.2%; SU 4.7 ± 3.0 (n = 37) vs. 7.4 ± 2.9 (n = 47) mg/dL].

In this uncontrolled gout population, approximately two-thirds of patients began oral ULT within 30 days after their last pegloticase infusion. Those with longer pegloticase course more often had oral ULT efficacy, perhaps because of greater urate burden depletion, suggesting oral ULTs may be effective after successful pegloticase therapy. Further studies to understand any influence of urate burden on oral ULT efficacy are warranted.

BACKGROUNDHyperinsulinemia and insulin resistance often accompany elevated serum urate levels (hyperuricemia), a highly heritable condition that triggers gout; however, the underlying mechanisms are unclear.METHODSWe evaluated the association between the index of hyperinsulinemia and the fractional excretion of urate (FEUA) in 162 outpatients. The underlying mechanisms were investigated through single-cell data analysis and kinase screening combined with cell culture experiments. In 377,358 participants of the UK Biobank (UKBB), we analyzed serum urate, hyperinsulinemia, and salt intake. We also examined gene-environment interactions using single nucleotide variants in SLC22A12, which encodes urate transporter 1 (URAT1).RESULTSThe index of hyperinsulinemia was inversely associated with FEUA independently of other covariates. Mechanistically, URAT1 cell-surface abundance and urate transport activity were regulated by URAT1-Thr408 phosphorylation, which was stimulated by hyperinsulinemia via AKT. Kinase screening and single-cell data analysis revealed that serum and glucocorticoid-regulated kinase 1 (SGK1), induced by high salt, activated the same pathway, increasing URAT1. Arg405 was essential for these kinases to phosphorylate URAT1-Thr408. In UKBB participants, hyperinsulinemia and high salt intake were independently associated with increased serum urate levels. We found that SLC22A12 expression quantitative trait locus (eQTL) rs475688 synergistically enhanced the positive association between serum urate and hyperinsulinemia.CONCLUSIONURAT1 mediates the association between hyperinsulinemia and hyperuricemia. Our data provide evidence for the role of gene-environment interactions in determining serum urate levels, paving the way for personalized management of hyperuricemia.FUNDINGACRO Research Grants of Teikyo University; Japan Society for the Promotion of Science; the Japanese Society of Gout and Uric & Nucleic Acids; Fuji Yakuhin; Nanken-Kyoten; Medical Research Center Initiative for High Depth Omics.

The association between low-carbohydrate diets and hyperuricemia risk, a significant risk factor for gout and cardiometabolic morbidities, remains inconclusive, partly due to differing effects of replacing carbohydrates with animal- or plant-based macronutrients. This study examined associations between low-carbohydrate diet patterns and hyperuricemia risk in 39,880 adults in the Korea National Health and Nutritional Examination Study 2016-2022.

Diet was assessed via a 24-hour dietary recall. The overall, animal-rich, and plant-rich low-carbohydrate diet score (LCDS) was calculated based on percent energy derived from protein and fat in animal and plant food sources. Hyperuricemia was defined as serum uric acid levels > 7.0 mg/dL for men and > 6.0 mg/dL for women. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models to estimate the risk of hyperuricemia across quintiles of LCDS.

A significantly greater risk of hyperuricemia was observed among individuals with higher overall LCDS (OR for quintile 5 vs. quintile 1 [Q5vs.Q1]: 1.41, 95%CI:1.22-1.63, P-trend: <0.001) and animal-rich LCDS (ORQ5vs.Q1: 1.28, 95%CI:1.12-1.47, P-trend: <0.001), but not with plant-rich LCDS (ORQ5vs.Q1: 1.00, 95%CI: 0.87-1.16). These positive associations for overall LCDS and animal-rich LCDS were evident in overweight individuals (ORQ5vsQ1: 1.53, 95%CI: 1.29-1.82 for overall LCDS; and 1.39, 95%CI: 1.19-1.63 for animal-rich LCDS; all P-trends < 0.001), but not in non-overweight individuals (all P-interactions: <0.001).

In our study, animal-based low-carbohydrate diets were associated with a greater risk of hyperuricemia, while no association was observed for plant-based low-carbohydrate diets. Larger cohort studies are warranted to replicate these findings.

Gout is the most common form of inflammatory arthritis in adults worldwide. There has been a steady increase in prevalence, which varies across different geographic areas and is high in the Indigenous (First Nations) peoples of the Pacific region. Palaeo-archaeological studies demonstrate that gout was present in the Pacific region prior to European colonization, which is suggestive of genetic predisposition. Genetic risk factors, including population-specific genetic variants and genetic variants shared across populations, particularly those influencing urate transporters, have been identified in Indigenous peoples of the Pacific that partly explain the earlier age of onset of gout. Indigenous peoples of the Pacific experience severe gout, with frequent flares, high hospitalization rates and tophaceous gout, all aggravated by socio-cultural factors. Despite a specific need for effective gout management, Indigenous peoples of the Pacific are under-represented in gout research and inequities in care continue. Indigenous peoples-led, holistic gout management programmes are systematically and urgently required in this region, where gout is a major public health issue. Importantly, a foundation of cultural safety is necessary to underpin such programmes.

Purine is a major factor contributing to the development of hyperuricemia and gout, and it is found in large quantities in Huangjiu as free bases. Purine production in Huangjiu is strongly associated with microbial metabolism. However, to the best of our knowledge the microorganisms responsible for and the mechanisms of purine formation during Huangjiu fermentation are yet to be evaluated. Herein, changes in purine levels during Huangjiu fermentation were analyzed. Further, the microbes responsible for purine production were identified and their gene abundance was studied. Results revealed that adenine, guanine, hypoxanthine, and xanthine are produced during Huangjiu fermentation. The total purines content on day 0 (27.99 mg/L) was found to be considerably lower than that produced on day 24 (122.15 mg/L) during Huangjiu fermentation. Metagenomics showed that the composition of the microbial community fluctuates sharply during five fermentation periods of Huangjiu, with the microbial community richness and diversity being the most prominent on day 3. At the genus level, Klebsiella, Lactobacillus, Staphylococcus, Saccharopolyspora, and Saccharomyces were abundant during Huangjiu fermentation and were involved in purine metabolism. Relationships between the dominant microorganisms and key enzyme genes of the purine pathways were also established based on the Kyoto Encyclopedia of Genes and Genomes database. Correlation analysis showed that Lactobacillus and Saccharomyces were the main genera involved in purine formation. Saccharomyces cerevisiae, Lactobacillus paralimentarius, and Lactiplantibacillus plantarum were involved in purine formation during Huangjiu fermentation. Overall, this study improves our understanding of the purine formation mechanism during Huangjiu fermentation and provides valuable insights into the regulation of purine formation by microorganisms.

Beer, the most popular alcoholic beverage, poses health risks for individuals with gout and hyperuricemia due to its high purine content. Herein, we identified a novel purine nucleoside phosphorylase (AbPNP) from the edible mushroom Agaricus bisporus and heterologously expressed it in Pichia pastoris. The recombinant AbPNP exhibited optimal activity at 60 °C and pH 7.0, retaining >80% activity at pH 6.0-9.0 and >85% activity after 3 h at ≤60 °C. Kinetic analysis revealed high catalytic efficiency (kcat/Km = 2.02 × 106 s-1⋅M-1) toward inosine, with strong resistance to metal ions except for Co2+ and Cu2+. The application of AbPNP (1.0-5.0 U/mL) during wort saccharification reduced purine nucleosides by 33.54% (from 151.53 to 100.65 mg/L) while increasing yeast utilization of free purine bases. The resulting beer showed improved fermentation performance (alcohol content increased by 3.6%) without compromising flavor profiles. This study provides the food-grade enzymatic strategy for low-purine beer production, leveraging the GRAS status of both A. bisporus and P. pastoris.

Hyperuricemia (HUA) is a metabolic disease characterized by elevated serum uric acid, which is closely related to the gut microbiota. Probiotics have great potential in improving HUA. The purpose of this study was to evaluate the effect and mechanism of probiotic product (SQK) containing Heyndrickxia coagulans TBC169 on HUA rats. Forty SD rats (6 weeks old, 200 ± 20 g) were randomly divided into four groups (Ctrl group, HUA group, SQK1 group, and SQK2 group) of 10 rats each. Rats were given potassium oxonate (100 mg potassium oxonate/100 g BW/day) for 12 weeks to establish HUA model and simultaneously administered with sterile saline (HUA group) or different dose of SQK (SQK1 group, 20.48 mg SQK/100 g BW/day; SQK2 group, 40.95 mg SQK/100 g BW/day) throughout the 12 weeks. The results showed that SQK could degrade uric acid precursors and inhibit the xanthine oxidase (XOD) activity in vitro. Oral supplementation of SQK can reverse the increase of serum uric acid, the increase of the liver and serum XOD activity, and the decrease of ABCG2 expression in the ileum induced by HUA. In addition, SQK could restore the changes in α and β diversity of the ileal microbiota and prevent the increase in pathogenic Helicobacter and Staphylococcus caused by HUA. 16S rRNA sequencing and correlation analysis showed that the chondroitin sulfate (CS) degradation pathway of the gut microbiota played a key role in the prevention of HUA in the SQK group. These findings suggest that SQK may improve HUA by reducing uric acid synthesis and increasing uric acid excretion and provide a basis for its development into a probiotic product to improve HUA.

Elevated serum uric acid levels are the essential pathophysiology of gout. Although gout rarely develops in childhood, chronic persistent hyperuricemia can induce precipitation and deposition of sodium urate crystals, leading to the development of gout. Hyperuricemia is caused by increased uric acid production and/or decreased uric acid excretion capacity of the kidneys and/or intestinal tract. Increased production of uric acid, the final metabolite of purine, is associated with an increase of phosphoribosyl pyrophosphate, the key compound in the purine synthesis pathways, as observed in hypoxanthine-guanine phosphoribosyltransferase deficiency. Another mechanism for increased uric acid production is increased adenosine triphosphate consumption that is found in glycogen storage disease type I. On the other hand, in uromodulin-associated kidney disease, the accumulation of abnormal uromodulin in the kidneys leads to tubulointerstitial damage and fibrosis, and the ability to excrete uric acid is compromised, with reduced secretion and increased reabsorption in the proximal tubules. Decreased uric acid excretion from the kidneys or intestinal tract is also mediated by decreased function of the ATP-binding cassette subfamily G member 2, a urate transporter that acts in the urate secretion. This review summarizes the selected pathophysiological mechanisms underlying the genetic basis of hyperuricemia and gout in children, both in terms of purine metabolism and uric acid excretion.

Gout is characterized by deposition of monosodium urate (MSU) crystals in or around joints, tendons, bursae, and other tissues, resulting in painful recurrent flares and tissue damage. Gout is the most common form of inflammatory arthritis, with a prevalence of 5.1% in the United States, affecting 12.1 million adults. When urate levels exceed the limit of solubility (6.8 mg/dL [400 μmol/L]), MSU crystals may form or grow. Gout flares are the result of inflammatory responses to MSU crystals. The primary method to prevent and reduce gout flares, tophi, chronic inflammatory arthritis, and joint damage is to reduce urate levels below the saturation threshold. The pathophysiology of gout is well understood, and inexpensive and effective therapies are available. However, outcomes for patients with gout remain poorly optimized.

Our objective was to evaluate associations of weight reduction with serum urate (SU) changes and achieving an SU level <6 mg/dL in the real-world setting, outside of specific weight reduction interventions.

We analyzed systematically collected data of annual medical examination participants from October 2012 to October 2022. Exposure was weight change (increase or decrease) between two consecutive visits, categorized as minimal (≤0.9 kg, reference), small (1.0-4.9 kg), moderate (5.0-9.9 kg), and large (≥10 kg). Outcomes included SU changes between two consecutive visits and achieving an SU level <6 mg/dL in participants with hyperuricemia (SU level ≥7 mg/dL at the previous visit).

We identified 58,630 eligible participants (median age 46 years, 51.3% female, 19.4% with overweight, median SU level 5.3 mg/dL, and 5.6% with a history of gout and/or hyperuricemia) with 336,814 visits over a median of 5.3 years. After adjustment for relevant covariates, linear general estimating equations estimated mean SU changes based on observed weight reductions (vs minimal changes) were as follows: small, -0.10 mg/dL (95% confidence interval [CI] -0.10 to -0.09 mg/dL); moderate, -0.34 mg/dL (95% CI -0.36 to -0.32 mg/dL); and large, -0.64 (95% CI -0.70 to -0.58 mg/dL). In participants with hyperuricemia, adjusted relative risks for achieving an SU level <6 mg/dL by modified Poisson regression were 1.25 (95% CI 1.15-1.37) in small weight reductions, 2.82 (95% CI 2.43-3.27) in moderate weight reductions, and 5.27 (95% CI 4.15-6.70) in large weight reductions, with corresponding numbers needed to treat of 61.1 for small weight reductions, 8.5 for moderate weight reductions, and 3.6 for large weight reductions.

Small weight reductions were associated with only small SU changes. Some participants with hyperuricemia can achieve the target SU level with moderate to large weight reductions.

Heart failure (HF) is a terminal stage of cardiovascular diseases, classified based on ejection fraction. Serum uric acid (SUA) has been implicated in the pathogenesis and progression of coronary artery disease (CAD) with HF, yet its predictive value remains unclear. This study aimed to evaluate the predictive role of SUA in the progression of HF in CAD patients and its potential to differentiate HF types. A retrospective analysis was conducted on 342 CAD patients, including 29 with CAD alone and 313 with CAD complicated by varied HF types. Biochemical parameters and HF severity were assessed, and logistic regression analyses were performed to identify independent predictors of HF progression. Significant differences were observed in biochemical parameters, including glutamic-pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), creatine kinase-MB (CK-MB), SUA, lactate dehydrogenase (LDH), myoglobin (MTO), between groups. SUA levels were significantly higher in CAD patients with HF, particularly in those with reduced ejection fraction. Univariate and multivariate logistic regression analyses identified history of hypertension, AST, and SUA as independent predictors of HF progression, with SUA showing the highest odds ratio. In addition, SUA levels were positively correlated with Gensini scores, indicating its association with CAD severity. SUA is a strong predictor of HF progression in CAD patients, especially for patients with HFrEF, which can serve as a diagnostic and prognostic marker for HF progression in CAD patients.

The association of food-sourced Coenzyme Q10(CoQ10) intake with hyperuricemia (HUA) remains unclear. We aimed to investigate the association between dietary CoQ10 intake and HUA among Chinese adults.

A total of 7953 Chinese adults from the 2009 China Health and Nutrition Survey (CHNS) were included in the present cross-sectional. Dietary CoQ10 was assessed by 3 consecutive 24-h dietary recall interviews combined with a household food inventory. Multivariable logistic regression models and restricted cubic spline models were used to explore the associations between dietary CoQ10 and HUA.

In an adjusted logistic regression model, the multivariable odds ratio (OR) and 95% confidence interval (CI) for HUA in the highest versus the lowest quartile of total, animal-based, and plant-based CoQ10 intake were 1.40 (95% CI: 1.15 to 1.70), 1.46 (95% CI: 1.20 to 1.78), and 0.80 (95% CI: 0.65 to 0.97), respectively. Dose-response analyses revealed similar linear patterns, with the exception of plant-derived CoQ10, which did not reach statistical significance (p for nonlinearity = 0.09). In stratified analysis, there were no significant interactions between sex, age, BMI, smoking status, drinking status and total dietary CoQ10 intake in relation to the HUA (All p for interaction > 0.05).

Our study documented a novel positive association between total dietary CoQ10 intake and HUA, with similar trends for animal-derived CoQ10 and an inverse trend for plant-derived CoQ10.

Oxidative stress and neuroinflammation are recognized as key factors in the development of neurodegenerative diseases, yet effective interventions and biomarkers to address oxidative stress and neuroinflammation in these conditions are limited. Uric acid (UA), traditionally associated with gout, is now gaining prominence as a potential target in neurodegenerative diseases. Soluble UA stands out as one of the most vital antioxidant compounds produced by the human body, accounting for up to 55% of the extracellular capacity to neutralize free radicals. While there is increasing evidence supporting the neuroprotective properties of UA in Parkinson's disease and Alzheimer's disease, gaps in knowledge still exist regarding the underlying mechanisms and how to effectively translate these benefits into clinical practice. Moreover, the current UA elevation therapy exhibits unstable antioxidant properties, individual variability, and even adverse effects, limiting its potential clinical applications. This review consolidates recent advancements in understanding how UA exerts neuroprotective effects on neurodegenerative diseases and emphasizes the dual roles of UA in managing oxidative stress and neuroinflammation. Additionally, the review elucidates the mechanisms through which UA confers neuroprotection. Based on this, the review underscores the significance of UA as a potential biomarker and aims to provide a comprehensive understanding of its potential as a therapeutic target, while also addressing possible challenges to clinical implementation.

Limited studies have suggested an effect of dietary choline intake on uric acid levels. We aim to investigate the associations between choline intake and hyperuricemia (HUA), as well as the mediating role of kidney function in this relationship, among the Chinese population aged 6-17 years.

Participants were divided into quartiles according to residual energy-adjusted dietary choline intake in our cross-sectional study. Dietary choline intake was assessed using the 24-h dietary recalls method over three consecutive days, including two weekdays and one weekend day. The primary outcome was the HUA prevalence. Based on recommendation in Clinical Paediatric Nephrology (3rd ed), HUA is defined based on fasting serum uric acid levels, with cutoffs varying by age and sex. The associations between choline intake and HUA were analysed using weighted logistic regression models, restricted cubic spline models, and linear regression models. The mediated proportions of estimated glomerular filtration rate (eGFR) in the associations were estimated with mediation effect models. The data for this study were collected from the China National Nutrition and Health Surveillance of Children and Lactating Mothers (2016-2017) conducted between October 2016 and December 2018. Eligible participants were identified through a database search conducted from October to December 2023.

Among the 10749 participants, 3398 (31.6%) individuals were found to have HUA. A negative dose-dependent relationship was found between dietary choline intake and HUA. Compared to participants in the lowest intake quartile of total choline, phosphatidylcholine, and betaine, those in the 4th quartile had lower odds of HUA, with odds ratio (OR) of 0.75 (95% confidence interval [95% CI], 0.63-0.90), 0.75 (95% CI, 0.64-0.89), and 0.75 (95% CI, 0.59-0.94), respectively. The eGFR mediated 10.60%-14.58% of the associations. Participants in the 4th quartile of lipid-soluble dietary choline exhibited 24.00% reduced odds of HUA compared to those in the lowest intake quartile, with an OR of 0.76 (95% CI, 0.64-0.90).

Moderate to high intake of dietary choline (181.20-357.92 mg/d), particularly phosphatidylcholine (120.22-207.58 mg/d), and betaine (189.24-282.37 mg/d), may reduce the odds of HUA by improving glomerular filtration function. Further interventional studies are needed to establish causal relationships.

This work was supported by the National Natural Science Foundation of China (82003443, 42375180), the Natural Science Foundation of Guangdong Province of China (2024A1515012088), and the Construction of High-level University of Guangdong (G624330422).

Gout is the most common inflammatory arthritis in adults, associated with hyperuricemia and the chronic deposition of monosodium urate (MSU) crystals. Hyperuricemia results from increased production of uric acid and decreased excretion by the kidneys and intestines. Urate excretion is regulated by a group of urate transporters, and decreased renal or intestinal excretion is the primary mechanism of hyperuricemia in most people. Genetic variability in these urate transporters is strongly related to variances in serum urate levels. Not all individuals with hyperuricemia show deposition of MSU crystals or develop gout. The initiation of the inflammatory response to MSU crystals is mainly mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing protein 3 (NLRP3) inflammasome. The activated NLRP3 inflammasome complex cleaves pro-interleukin-1β (IL-1β) into its active form, IL-1β, which is a key mediator of the inflammatory response in gout. IL-1β leads to the upregulation of cytokines and chemokines, resulting in the recruitment of neutrophils and other immune cells. Neutrophils recruited to the site of inflammation also play a role in resolving inflammation. Aggregated neutrophil extracellular traps (NETs) trap and degrade cytokines and chemokines through NET-bound proteases, promoting the resolution of inflammation. Advanced gout is characterized by tophi, chronic inflammatory responses, and structural joint damage. Tophi are chronic foreign body granuloma-like structures containing collections of MSU crystals encased by inflammatory cells and connective tissue. Tophi are closely related to chronic inflammation and structural damage.

Serum levels of uric acid (S-UA) are influenced by the interaction of genetic and environmental factors; detailed studies of hyperuricemia in children are rare. This retrospective study aimed to analyze the causes, risk factors, and therapeutic approaches associated with the development of hyperuricemia in childhood.

In a single-center study, serum uric acid levels were analyzed in 33,900 samples from 13,890 children and adolescents<19 years (6760 girls and 7130 boys) obtained between 2013 and 2023. Hyperuricemia was defined as S-UA>370μmol/L (6.22mg/dL) in girls and>420μmol/L (7.06mg/dL) in boys; mild hyperuricemia was defined as 370-420μmol/L in boys<13 years.

In the analyzed group, hyperuricemia was found in 1753 patients (12.6%), including 586 girls and 864 boys; mild hyperuricemia was found in 303 boys<13 years. The most common associated conditions were obesity with body mass index>95th percentile (27.8% of girls, 26.3% of boys) and chronic kidney disease (18.6% of boys, 11.4% of girls). Hyperuricemia was also relatively common in children with connective tissue disorders (10.6%) or different inherited metabolic disorders (10.7%). Transitory hyperuricemia was found in 19.1% of girls and 10.1% of boys with acute gastroenteritis. Urate-lowering therapy was used in 73 children and adolescents with severe hyperuricemia (S-UA 556±107μmol/L, fraction excretion of UA 3.27±1.98%). Eight treated children had chronic kidney disease, nine were extremely obese, one had combined antiepileptic therapy, and 55 had inherited metabolic diseases, including 26 children with disorders of purine metabolism. The initial daily dose of allopurinol (50-100mg) normalized the S-UA (350±80μmol/L) in a majority of children, except for extremely obese adolescents (weight 98-149kg) where the dose had to be increased to 200-300mg.

Asymptomatic hyperuricemia is a relatively common biochemical finding in pediatric clinical practice. The etiology of hyperuricemia should be carefully analyzed, and the value of individualized hyperuricemia management and the eventual benefits of urate-lowering therapy in children must be carefully considered.

Gout is one of the oldest known diseases and the most common form of inflammatory arthritis. The established risk factors for gout include hyperuricemia, chronic renal disease, genetic, alcohol consumption, dietary factors, diuretic use, hypertension, obesity, and metabolic syndrome. Patients with gout have an increased risk of all-cause mortality, particularly from cardiovascular disease, cancer, and infectious diseases. Gout is also associated with several complications, such as nephrolithiasis. This literature review describes the global epidemiology and trends associated with gout, before providing an overview of its risk factors and complications.

This research used the narrative review method. Thorough searches were performed in PubMed and Google scholar, up to June 15, 2024, for articles that evaluated the risk factors, comorbidities or complications associated with gout. Moreover, we also included studies that reported the epidemiological characteristics or burden of gout at the global, regional, or national level.

Gout is more prevalent in developed countries, than in developing countries, although its prevalence is increasing globally. In addition, gout is much more prevalent among males than among females. Hyperuricemia has the largest role in the development of gout, although many risk factors contribute to the increasing prevalence of gout, including genes, several medications, and diet. Gout is associated with several comorbidities and complications, which need to be taken into consideration when managing gout. In recent years, gout has been found to be associated with several new comorbidities.

Our findings provide a comprehensive and informative overview that can be useful for the prevention, diagnosis, and management of gout.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age and is associated with a variety of multi-system complications. The prevailing treatment strategy for PCOS is to individualize the interventions based on individual symptoms and patient complaints. However, optimal efficacy in treatment necessitates a focus on addressing the underlying pathogenic mechanisms. Uric acid (UA), the end product of purine metabolism, has been suggested to be involved in the development of several diseases, including PCOS. However, the precise mechanisms by which UA may affect PCOS remain incompletely understood. This literature review aims to investigate the correlation between UA and the various clinical presentations of PCOS, such as hyperandrogenism, insulin resistance (IR), ovulation disorders, obesity, and other related manifestations, through the analysis of epidemiological and clinical studies. The purpose of this study is to improve our comprehension of how UA contributes to each aspect of PCOS and their interrelationship, thus identifying the potential role of UA as a facilitator of PCOS. Furthermore, we explore potential pathways linking UA and PCOS, and propose therapeutic interventions based on these findings to optimize the management of this condition.

Serum uric acid (SUA) has been linked to mortality in heart failure, hypertension, diabetes, hyperlipidemia, obstructive sleep apnea, and metabolic dysfunction-associated fatty liver disease. However, data are lacking on how it affects the mortality risk of patients with cardiovascluar disease (CVD). This study evaluated the data of 4 308 individuals from the National Health and Nutrition Examination Survey 1999-2008 using multivariate Cox proportional hazards regression, trend, restricted cubic splines (RCS), subgroup and inflection point analyses. All-cause and cardiovascular mortality accounted for 42.8% and 17.6% of cases, respectively, over a median 80- month follow-up. Upon control for confounding variables, no linear trend was seen in the Cox proportional hazards regression analysis between SUA and all-cause (P = 0.001) or cardiovascular death (P = 0.007) mortality. On the RCS analysis, SUA showed an L-shaped connection with all-cause (non-linear P < 0.001) and cardiovascular mortality (non-linear P = 0.003) mortality. On the inflection point analysis, patients with CVD and an SUA ≥ 6.127 mg/dL had an all-cause mortality hazard ratio of 1.146 (95% confidence interval, 1.078-1.217; P < 0.001), while those with CVD and an SUA ≥ 5.938 mg/dL had a cardiovascular mortality hazard ratio of 1.123 (95% confidence interval, 1.03-1.225; P = 0.007). In patients with CVD, higher SUA was non-linearly correlated with all-cause and cardiovascular mortality.

Early-onset gout (EOG) is characterized by the occurrence of the first symptoms of gout at an unusually young age, usually <40 years. The aim of this review is to provide an overview of the epidemiology, clinical presentation and prognosis, association with comorbidities and specific management of EOG. A particularly high proportion of patients with EOG come from ethnic groups with stronger genetic factors, such as populations in the Pacific and Taiwan, who therefore have the highest prevalence of gout overall. The clinical presentation and severity of gout are broadly similar between EOG and common gout, although a longer disease duration exacerbates the disease, which more often tends to become polyarticular. Patients suffering from EOG develop metabolic comorbidities commonly associated with gout earlier in life, although those tend to be less frequent at the time of diagnosis. Some international guidelines recommend early treatment of EOG patients with urate-lowering therapies.

Background: Scientific societies disagree on serum uric acid (SUA) thresholds for the diagnosis of hyperuricaemia (HU) according to epidemiological or physiochemical criteria (SUA ≥ 7.0 mg/dL for men and ≥6.0 mg/dL for women [HU-7/6]; SUA ≥ 7.0 mg/dL for both genders [HU-7/7], respectively). HU is not included among the diagnostic criteria for metabolic syndrome or cardiovascular-renal-metabolic syndrome (CKM), although it promotes atherosclerosis and is associated with renal and cardiometabolic diseases. Both issues are of utmost importance and need to be clarified, hence the present study aims to assess the prevalence rates of HU and their associations with CKM factors. Methods: A cross-sectional observational study was conducted on a random population-based sample of 6489 adults. Bivariate and multivariate analyses were performed on the most well-known renal and cardiometabolic variables of the populations with and without HU-7/7 and HU-7/6. Results: The adjusted prevalence rates for HU-7/6 were 13.4% in adult population (18.4% in men; 9.6% in women) and 10.2% (18.4% in men; 3.8% in women) for HU-7/7. The main factors associated independently with HU for both genders were low estimated glomerular filtration rate, hypertension, hypertriglyceridaemia, and alcoholism, regardless of the criteria chosen, as well as albuminuria in women and central obesity in men. Conclusions: The prevalence rates of HU increase linearly with age for both genders. The associations of CKM factors with HU diagnosed according to physiochemical criterion are more similar between men and women than those using epidemiological criteria.

The study aimed to explore the risk factors for hyperuricemia (HUA) in the Naxi ethnic population residing in high-altitude areas of Yunnan, China, and assess the clinical value of the triglyceride/high-density lipoprotein cholesterol (TG/HDL-c) ratio as a diagnostic marker.

In this cross-sectional study, clinical data were collected from the health checkup population in the People's Hospital of Yulong Naxi Autonomous County, Yunnan Province, from January 2021 to January 2023. Participants were divided into quartiles based on the TG/HDL-c ratio (Q1, Q2, Q3, and Q4) for group analysis using chi-square tests, t-tests, and rank sum tests. Logistic regression analysis and linear regression models were employed to further investigate the correlation between the prevalence of hyperuricemia and TG/HDL-c ratio in this high-altitude Naxi population.

A total of 714 participants from the health checkup population were included in the study, of whom 61.5% were male participants and 38.5% were female participants, and the average age was 41.21 ± 11.69 years. The mean uric acid level was 388.51 ± 99.24. After correcting for confounding factors, TG/HDL-c, serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), red blood cells (RBCs), and hemoglobin (Hb) showed a positive correlation with blood uric acid. Further analysis involved categorizing the TG/HDL-c ratio from a continuous variable to a categorical variable using quartiles. The fully adjusted model showed results that were consistent with the trend observed in the continuous variable analysis when considering the TG/HDL-c ratio as a categorical variable. In addition, in all unadjusted and adjusted models, the serum uric acid (SUA) levels in the high TG/HDL-c ratio group were significantly higher than those in the low TG/HDL-c ratio group (trend p < 0.001). Further linear relationship analysis indicated that after adjusting for covariates, there was an approximate linear relationship between the TG/HDL-c and SUA levels, with a coefficient (β) of 5.421.

The prevalence of hyperuricemia is greater in high-altitude areas of Yunnan, showing a nearly linear positive correlation with the TG/HDL-c ratio. Monitoring TG/HDL-c levels may benefit patients with hyperuricemia.

The synthesis of cobalt nanocrystal-graphene quantum dot-Ti3C2TX monolithic film electrode (Co-GQD-Ti3C2TX) is reported via self-assembly of Ti3C2TX nanosheets induced by protonated arginine-functionalized graphene quantum dot and subsequent reduction of cobalt (III). The resulting Co-GQD-Ti3C2TX shows good monolithic architecture, mechanical property, dispersibility and conductivity. The structure achieves excellent supercapacitor and sensing behavior. The self-charging supercapacitor produced by printing viscous Co-GQD-Ti3C2TX hydrogel on the back of flexible solar cell surface provides high specific capacitance (296 F g-1 at 1 A g-1), high-rate capacity (153 F g-1 at 20 A g-1), capacity retention (98.1% over 10,000-cycle) and energy density (29.6 W h kg-1 at 299.9 W kg-1). The electrochemical chip produced by printing Co-GQD-Ti3C2TX hydrogel on paper exhibits sensitive electrochemical response towards uric acid. The increase of uric acid between 0.01 and 800 μM causes a linear increase in differential pulse voltammetry signal with a detection limit of 0.0032 μM. The self-powered sensing platform integrating self-charging supercapacitor, electrochemical chip and micro electrochemical workstation was contentedly applied to monitoring uric acid in sweats and shows one broad application prospect in wearable electronic health monitoring device.

Although previous studies have explored the association of drinking with gout risk, we sought to explore the dose-response relationship and the evidence between subtypes of alcoholic beverages and gout risk.

The weekly alcoholic beverage consumption of patients in the UK Biobank was collected and calculated. The Cox regression model was applied to assess the effects of drinking alcohol in general and its subtypes on gout risk by calculating the hazard ratio (HR) and 95% CIs. Additionally, the restricted cubic splines were used to estimate the dose-response relationship between alcohol consumption and gout risk. To evaluate the robustness, we performed subgroup analysis across various demographic characteristics.

During a mean follow-up period of 11.7 years, a total of 5728 new incident gout cases were diagnosed among 331,865 participants. We found that light alcohol consumption was linked to a slight decrease in gout incidence among female individuals (HR 0.78, 95% CI 0.65-0.94, P = 0.01), whereas there was no significant association in male individuals. Moreover, the dose-response relationship showed that drinking light red wine and fortified wine could reduce the gout risk, whereas beer or cider, champagne or white wine, and spirits increased the gout risk at any dose.

Our study suggested a J-shaped dose-response relationship between drinking and gout risk in female individuals, but not in male individuals. For specific alcoholic beverages, light consumption of red wine and fortified wine was associated with reduced gout risk. These findings offer new insights into the roles of alcoholic beverages in gout incidence risk, although further validation is warranted.

The nucleic acids found in food play a crucial role in maintaining various bodily functions. This study investigated the potential anticancer effects of dietary nucleic acids, an area that is still not fully understood. By utilizing an in vivo mouse model and an in vitro cell model, we discovered an anti-proliferative impact of RNA in both systems. DNA exhibited anti-proliferative effects in the mouse model, while this phenomenon wasn't observed in the in vitro cell model using Ehrlich ascites tumor (EAT) cells. Conversely, DNA hydrolysate demonstrated distinct anti-proliferative effects in EAT cells, suggesting that nucleotides or nucleosides generated during nucleic acid digestion act as active constituents. Furthermore, we examined various nucleosides and two sodium-independent equilibrative nucleoside transporter inhibitors (ENTs), identifying guanosine and 2'-deoxyguanosine as pivotal in the anti-proliferative effect. We also found that the anti-proliferation activity with both nucleosides was suppressed by the treatment of dipyridamole, a non-selective inhibitor for ENT1 and ENT2, but not nitrobenzylthioinosine, a low inhibitor for ENT2. The uptake of these compounds into cells is likely facilitated by ENT2. These nucleotides impeded the progression of cancer cells from the G1 phase to the S phase in the cell cycle. Another significant finding is the increased expression of CCAAT/enhancer-binding protein (C/EBPβ) induced by guanosine and 2'-deoxyguanosine. Furthermore, immunostaining revealed that C/EBPβ diffuses into the nucleus, indicating its presence. This suggests that guanosine or 2-deoxyguanosine induces G1 arrest in cancer cells via the activation of C/EBPβ. Encouraged by these promising results, guanosine and 2'-deoxyguanosine show potential applications in cancer prevention.

Despite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change.

We conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates.

We analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (-0.019 (95% CI: -0.021 to -0.017) mg/dL). Beer had the largest association with SU (-0.036 (95% CI: -0.039 to -0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with -0.056 mg/dL (95% CI: -0.068 to -0.043) decrease in SU; the association became larger in hyperuricemic participants (-0.110 mg/dL (95% CI: -0.154 to -0.066) for alcohol discontinuation from a mean of 1.0 drinks/day).

This study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

To investigate the association between serum uric acid and women's ovarian reserve.

Retrospective observational study and Mendelian randomization study.

University-affiliated in vitro fertilization center.

Observational analyses were undertaken using data from 8,257 women with infertility who finished their first in vitro fertilization treatments between May 2017 and December 2021. Mendelian randomization analyses were based on genome-wide association summary statistics from several biobanks of predominantly European ancestries.

Observational study involved testing log2 transformed serum uric acid levels (for linear, negative regression, and logistic regression analyses); original uric acid levels (for nonlinear association analyses). Mendelian randomization study involved testing genetically predicted uric acid levels.

Biomarkers including antimüllerian hormone, basal antral follicle count, follicle-stimulating hormone, luteinizing hormone, ratio of follicle-stimulating hormone to luteinizing hormone, estradiol; indices of ovarian response to stimulation including poor ovarian response according to different criteria and oocyte yield.

In retrospective observational study, all ovarian reserve-related outcomes demonstrated significant differences across serum uric acid quartiles. A two-fold uric acid increase was associated with increased antimüllerian hormone (adjusted β = 0.69; 95% confidence interval [CI], 0.43-0.95), antral follicle count (adjusted incidence rate ratio = 1.10, 95% CI, 1.05-1.14), luteinizing hormone (adjusted β = 0.53, 95% CI, 0.28-0.78), decreased risks of Bologna poor ovarian response (adjusted odds ratio = 0.97; 95% CI, 0.95-0.99) and groups 2-4 Poseidon poor ovarian response (group 2: 0.63, 0.56-0.71; group 3: 0.71, 0.65-0.78; group 4: 0.50, 0.46-0.55), whereas an increased risk of group 1 (1.26, 1.13-1.41). Nonlinear analyses showed a common inflection point at 320-340 μmol/L of uric acid. Interactions between uric acid and antimüllerian hormone and antral follicle count were presented in association with oocyte yield. Mendelian randomization results suggested a significant association between genetically predicted uric acid levels and antimüllerian hormone levels (β = 0.08; 95% CI, 0.04-0.12) but none for uric acid in relation to polycystic ovarian syndrome or other related hormones.

Higher uric acid levels were associated with better ovarian reserve and increased levels of antimüllerian hormone albeit an increased risk of unexpected poor ovarian response.

Nutritional therapy, for example through beer, is the best solution to human chronic diseases. In this article, we demonstrate the physiological mechanisms of the functional ingredients in beer with health-promoting effects, based on the PubMed, Google, CNKI, and ISI Web of Science databases, published from 1997 to 2024. Beer, a complex of barley malt and hops, is rich in functional ingredients. The health effects of beer against 26 chronic diseases are highly similar to those of barley due to the physiological mechanisms of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. Functional beer with low purine and high active ingredients made from pure barley malt, as well as an additional functional food, represents an important development direction, specifically, ginger beer, ginseng beer, and coix-lily beer, as consumed by our ancestors ca. 9000 years ago. Low-purine beer can be produced via enzymatic and biological degradation and adsorption of purines, as well as dandelion addition. Therefore, this review paper not only reveals the physiological mechanisms of beer in overcoming chronic human diseases, but also provides a scientific basis for the development of functional beer with health-promoting effects.

Hyperuricaemia (HUA) poses a significant public health challenge on a global scale. It is mostly asymptomatic hyperuricemia (AHU) with unsatisfactory recognition and control rates. The role of health literacy in influencing health outcomes is of utmost importance, and enhancing health literacy is helpful for patients in managing risk factors. Additionally, social support and socioeconomic position (SEP) have been identified as potential factors influencing health. However, the exact relationships between these factors and AHU remain unclear. This study aimed to investigate the status of health literacy among patients with AHU and explore the relationships between health literacy, social support, SEP, and serum uric acid (SUA) levels.

A cross-sectional study was conducted among 349 participants with AHU in Luzhou, China. The research instruments included a sociodemographic characteristics questionnaire, the Health Literacy Scale for Chronic Patients (HLSCP), and the Social Support Scale (SSRS). The construction of the SEP index was achieved through the application of principal component analysis. Univariate and hierarchical regression analyses were used to evaluate the associations between SEP, social support, health literacy, and SUA levels. Furthermore, structural equation modelling (SEM) was utilized to examine these associations.

(1) Most patients exhibited low health literacy (90.18 ± 15.11), and only 44.4% possessed basic health literacy. (2) SEP was positively correlated with SUA levels (β = 4.086, P < 0.001), and health literacy was negatively related to SUA levels (β = -0.399, P < 0.001). There was no significant relationship between social support and SUA levels (β = 0.051, t = 1.085). (3) Health literacy mediated the association between SEP and SUA levels (β = -0.490, 95% CI: -0.620 to -0.382). SEP had a direct positive effect on SUA levels (β = 0.723) and health literacy (β = 0.696), and the total effect of SEP on SUA levels was 0.233.

The findings indicate a low level of health literacy among patients with AHU and suggest that health literacy might play a mediating role in the relationship between SEP and SUA levels. Consequently, future initiatives are recommended to prioritize health literacy and devise appropriate intervention strategies to enhance the self-management capabilities of patients with AHU.

Xanthine Oxidoreductase (XOR) is a ubiquitous, essential enzyme responsible for the terminal steps of purine catabolism, ultimately producing uric acid that is eliminated by the kidneys. XOR is also a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various physiological pathways, as well as contribute to the development and the progression of chronic conditions including kidney diseases, which are increasing in prevalence worldwide. XOR activity can promote oxidative distress, endothelial dysfunction, and inflammation through the biological effects of reactive oxygen species; nitric oxide and uric acid are the major products of XOR activity. However, the complex relationship of these reactions in disease settings has long been debated, and the environmental influences and genetics remain largely unknown. In this review, we give an overview of the biochemistry, biology, environmental, and current clinical impact of XOR in the kidney. Finally, we highlight recent genetic studies linking XOR and risk for kidney disease, igniting enthusiasm for future biomarker development and novel therapeutic approaches targeting XOR.

Limited data regarding the correlation between oxidative balance score (OBS) and hyperuricemia highlights the necessity for thorough investigations. This study aims to examine the link between OBS, which incorporates dietary and lifestyle factors, and the occurrence of hyperuricemia.

We conducted a cross-sectional study involving 13,636 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The oxidative balance score (OBS) was determined based on four lifestyle factors and sixteen dietary nutrients. We assessed the levels of serum uric acid (SUA) and the occurrence of hyperuricemia as outcomes. Weighted logistic regression and linear models were used for statistical analysis, using Restricted Cubic Splines (RCS) to examine potential nonlinear associations. Subgroup analysis and sensitivity assessments were performed to identify any variations and ensure the robustness of the findings.

Higher OBS was consistently correlated with decreased SUA levels and a reduced prevalence of hyperuricemia. RCS highlighted a significant negative nonlinear association, particularly in females. Subgroup analysis revealed gender-based differences and interactive correlation, providing additional insights regarding OBS and hyperuricemia relationship.

This study underscores a robust negative correlation between OBS and SUA levels as well as the incidence of hyperuricemia, emphasizing the importance of dietary and lifestyle factors. Incorporating RCS, subgroup analysis, and sensitivity assessments enhances the depth of our findings, providing valuable insights for further research.

Hyperuricemia (HUA) is a prevalent metabolic disorder whose development is associated with intestinal microbiota. Therefore, probiotics have emerged as a potential and safe approach for lowering uric acid (UA) levels. However, the underlying mechanisms of many effective probiotic strains remain unknown.

C57BL/6 mice were randomly divided into two groups: control and model groups. The model group received 12 weeks of potassium oxonate. Through 16s sequencing we found that HUA resulted in a significant decrease in the total diversity of all intestinal segments. When each intestinal segment was analyzed individually, the reduction in diversity was only significant in the cecum and colon sections. RDA analysis showed that lactobacilli in the rat colon exhibited a strong correlation with model group, suggesting that Lactobacillus may play an important role in HUA. Consequently, the preventive effects of Lactobacillus johnsonii YH1136 against HUA were investigated. C57BL/6 mice were randomly divided into three groups: control, model and YH1136 groups. The results showed that administering Lactobacillus johnsonii YH1136 effectively reduced serum UA levels in vivo by inhibiting hepatic xanthine oxidase (XOD) activity and promoting renal ABCG2 transporter expression. Moreover, supplementation with Lactobacillus johnsonii YH1136 significantly ameliorated pathological damage in the kidney and liver, thereby reducing UA accumulation.

Hyperuricemia is accompanied by an altered composition of multiple gut bacteria, of which Lactobacillus is a key genus. Lactobacillus johnsonii YH1136 may ameliorate renal involvement in HUA via the gut-kidney axis.

The association between hyperuricemia and cardiovascular diseases has been studied for many years. Research has shown a link between high uric acid levels and increased risk of including coronary artery disease hypertension and other cardiovascular conditions. Urate-lowering therapy, particularly with xanthine oxidase inhibitors like allopurinol, has shown promising results in reducing blood pressure in individuals with hyperuricemia and hypertension. Clinical trials and studies have demonstrated significant reductions in both systolic and diastolic blood pressure with urate-lowering treatment. Urate-lowering treatment has shown a favorable effect on reducing systolic blood pressure and major adverse cardiovascular events in patients with previous cardiovascular disease. In terms of cardiovascular safety, clinical trials have indicated that xanthine oxidase inhibitors such as febuxostat are non-inferior to allopurinol and do not increase the risk of death or serious adverse events. Overall, these findings highlight the importance of managing hyperuricemia and utilizing urate-lowering therapy to mitigate the adverse cardiovascular effects associated with elevated uric acid levels.

He, Ben, Jiayue Feng, Yan Shu, Lichun Yang, Zepin He, Kanxiu Liao, Hui Zhuo, and Hui Li. Prevalence and risk factors of hyperuricemia among young and middle-aged Tibetan men living at ultrahigh altitudes: a cross-sectional study. High Alt Med Biol. 25:42-48, 2024. Background: Few studies have examined the prevalence or risk factors of hyperuricemia among populations living at ultrahigh altitudes. Here we examined the prevalence of hyperuricemia and factors associated with it among young and middle-aged Tibetan men living at ultrahigh altitudes. Methods: This cross-sectional study analyzed 672 Tibetan men 18-60 years old living on the Qinghai-Tibet Plateau (mean altitude 4,014 m) within the county of Litang in the Ganzi Tibetan autonomous prefecture of Sichuan Province, China. Demographic and clinical data were collected from self-administered questionnaires, physical examinations and laboratory tests. Participants whose blood uric acid (UA) contained >420 μmol/l were classified as having hyperuricemia. Results: Of the 672 men analyzed, 332 (49.4%) had hyperuricemia. Multivariate logistic regression showed risk of hyperuricemia to correlate positively with body mass index (per 1 U increase: odds ratio [OR] 1.172, 95% confidence interval [CI] 1.1066-1.243), triglycerides (OR 1.408, 95% CI 1.084-1.828), red blood cell count (OR 1.376, 95% CI 1.009-1.875), and creatinine level (per 1 U increase: OR 1.051, 95% CI 1.033-1.070). Conversely, risk of hyperuricemia correlated negatively with the presence of diabetes mellitus (OR 0.412, 95% CI 0.175-0.968). Subgroup analyses showed that prevalence of hyperuricemia was significantly higher among those with polycythemia than among those without it, and that UA levels correlated positively with hematocrit and hemoglobin levels. Conclusions: Hyperuricemia is an important public health problem among Tibetan men living at ultrahigh altitudes in Ganzi autonomous prefecture. The region urgently requires appropriate prevention and management efforts.

Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, it remains unclear whether the observations are causal because of confounding factors.

To investigate the causal associations between urate levels and IBD using bidirectional Mendelian randomization (MR).

Independent genetic variants for urate levels and IBD were selected as instrumental variables from published genome-wide association studies (GWASs). Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD (the UK Biobank, the FinnGen database and a large GWAS meta-analysis) and one for urate levels (a large GWAS meta-analysis). MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger and sensitivity analyses (MR-PRESSO). A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model.

Genetically higher serum urate levels were strongly associated with an increased risk of UC [odds ratio (OR): 1.95, 95% confidence interval (CI): 1.86-2.05] after outlier correction, and the ORs (95%CIs) for IBD and CD were 0.94 (95%CI: 0.86-1.03) and 0.91 (95%CI: 0.80-1.04), respectively. Animal studies have confirmed the positive association between urate levels and UC. Moreover, genetically predicted IBD was inversely related to urate levels (OR: 0.97, 95%CI: 0.94-0.99). However, no association was observed between genetically influenced UC or CD and urate levels.

Urate levels might be risk factors for UC, whereas genetically predicted IBD was inversely associated with urate levels. These findings provide essential new insight for treating and preventing IBD.

The investigation of environmental effects on clinical measurements using individual samples is challenging because their genetic and environmental factors are different. However, using monozygotic twins (MZ) makes it possible to investigate the influence of environmental factors as they have the same genetic factors within pairs because the difference in the clinical traits within the MZ mostly reflect the influence of environmental factors. We hypothesized that the within-pair differences in the traits that are strongly affected by genetic factors become larger after genetic risk score (GRS) correction. Using 278 Japanese MZ pairs, we compared the change in within-pair differences in each of the 45 normalized clinical measurements before and after GRS correction, and we also attempted to correct for the effects of genetic factors to identify Cytosine-phosphodiester-Guanine (CpG) sites in DNA sequences with epigenetic effects that are regulated by genetic factors. Five traits were classified into the high heritability group, which was strongly affected by genetic factors. CpG sites could be classified into three groups: regulated only by environmental factors, regulated by environmental factors masked by genetic factors, and regulated only by genetic factors. Our method has the potential to identify trait-related methylation sites that have not yet been discovered.

We investigated the different life styles among the diet structures and exercise patterns of 100 patients with refractory gout and 79 healthy volunteers; of these, we selected 39 patients and 20 healthy volunteers for serum proton magnetic resonance (1H-NMR) metabolic network detection. We determined the potential biomarkers of refractory gout and attempted to explore the relation between potential biomarkers and diet structures and exercise patterns.

The study employed a questionnaire survey to analyze diet structures and exercise patterns from 100 patients of refractory gout and 79 healthy volunteers. At the same time, using 1H-NMR metabolic technology to analyze the metabolites present in the serum samples obtained from 39 patients of refractory gout (group B) and 20 healthy subjects (group A). Employing MestReNova (Version 8.0.1) to analyze the metabolites maps, collecting the NMR results, further importing into SIMCA-P+ 14.0 software (Umetrics, Sweden) for principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) statistical analysis. Combining patterns recognition and multivariate statistics, potential biomarkers were searched. Other experimental data, including creatinine and adiponectin, were counted by the SPSS21.0. The measurement data were expressed by X ± S and t test. The counting data were expressed in percent and performed by X2 test.

Our results revealed that patients with gout tended to be obese, and there were differences in their lifestyle with exercise, sleep, and smoking, as well as in their preference for fructose drinks, alcohol, and total and structural distribution of meat, milk, eggs, and so on when compared with the healthy volunteers. Importantly, we found the adiponectin in the gout group was lower as compared to the healthy group. Further, metabolomics in combination with KEGG analysis revealed that the biosynthesis of aminoacyl tRNA, biosynthesis of valine, leucine, and isoleucine, metabolism of alanine, aspartic, and glutamate, metabolism of glycine, serine, and threonine, phenylalanine, glycolysis/gluconeogenesis, ketone body synthesis and degradation, metabolism of D-glutamine, citric acid cycle (TCA cycle), triglyceride metabolism, and others could be used as specific biomarkers of this disease.

Recurrent refractory gout and formation of tophus may be related to the diet structures and lifestyles between the patients and the healthy people, and their abnormal metabolic network may be related to the disorder of mitochondrial energy metabolism, which further results in abnormal metabolism of glucose, lipids, amino acids, and deposition of uric acid in joints, peripheral connective tissue, and kidney, inducing an inflammatory response.

Hyperuricemia (HU) is a common disorder associated with gout, kidney injury, and high cardiovascular risk. However, whether high serum uric acid (sUA) is a causative factor or just comorbidity remains unclear. When asked if asymptomatic hyperuricemic patients need treatment, even artificial intelligence in the form of the GPT chat provides an ambivalent answer and refers us to a healthcare provider. We believe that such discrepancies stem from an incomplete understanding of the role that uric acid (UA) plays inside and outside the cell. With the rapid development of genomics, proteomics, immunology, and novel biomarkers, we are armed with new data to help us better understand the weight of inborn and environmental factors on an individual's UA concentrations. This review sums up the latest progress that has been made in the field of asymptomatic HU, compares the results presented by various research teams, and indicates new directions that emerge for future studies.

Obesity and hyperuricemia (HUA) often coexist and have been widely accepted as risk factors for hypertension, but the role of uric acid (UA) in the relationship between obesity and hypertension remains unknown in children and adolescents.

A total of 7525 subjects aged 6-16 years were from the School-based Cardiovascular and Bone Health Promotion Program (SCVBH) at baseline (2017) and followed up in 2019. Multivariable logistic regression with interaction terms, cross-lagged panel analysis, and causal mediation model were applied to delineate the joint impact of obesity and HUA on hypertension, including the interaction effect, the temporal association, and the mediating effect of UA in the relationship between obesity and hypertension. There were 10.8 % of the participants with normotension at baseline developed hypertension after two years of follow-up. Cross-lagged panel analysis showed that the two-time point association was significant only from baseline BMI to follow-up UA (β1 = 0.302, P < 0.001), but not from baseline UA to follow-up BMI (β2 = 0.002, P = 0.745). Multivariable logistic regression showed that both obesity and HUA increased the risk of hypertension, but no interaction effect between HUA and obesity. The causal mediation analysis found that UA partially mediated the association between BMI and SBP (mediate proportion: 20.3 %, 95 % CI: 17.4-22.9 %) or DBP (mediate proportion: 11.9 %, 95 % CI: 3.9-18.2 %). The results were consistent in the analysis of systolic hypertension rather than diastolic hypertension.

It is mediating effect that UA played in the progress from obesity to hypertension, particularly systolic hypertension in children and adolescents.