With the global aging trend escalating, the holistic well-being of the elderly has become a paramount concern within public health. Traditional observational studies often struggle with confounding factors and establishing causality, leaving the relationship between age-related hearing loss (ARHL) and gout largely unexplored. Employing bidirectional two-sample Mendelian randomization (MR) analysis, this investigation elucidated the genetic underpinnings associated with age-related hearing impairment, gout, and urate levels within the IEU Open-GWAS database, thereby uncovering potential causal connections that underlie the intricate interplay between gout, serum urate concentrations, and auditory decline in the geriatric demographic. In the forward MR phase, a cohort of 30 single nucleotide polymorphisms was leveraged to dissect the causal dynamics between ARHL and both gout and urate concentrations. Conversely, in the reverse MR phase, gout and urate levels were posited as the exposome to delineate their impact on hearing acuity, employing an array of models for rigorous validation and sensitivity scrutiny. In the forward MR analysis, a statistically significant correlation was discerned between ARHL and gout (P = .003, odds ratio = 1.01, 95% confidence interval: 1.00-1.02), alongside a notable association with serum urate levels (P = .031, odds ratio = 1.39, 95% confidence interval: 1.03-1.88), intimating that ARHL could potentially influence the incidence of gout and urate concentrations. Conversely, the reverse MR investigation revealed that neither gout nor serum urate levels exerted significant impact on auditory degradation (P > .05), insinuating that these factors might not predominantly contribute to hearing loss. Sensitivity analyses concurred with this inference. This study enriches the comprehension of geriatric health intricacies and unveils that ARHL potentially influences gout and serum urate concentrations. This suggests that monitoring ARHL may play a crucial role in the early identification and management of gout and hyperuricemia, potentially contributing to a comprehensive approach to improving geriatric health outcomes.

UNASSIGNED: As a natural antioxidant, uric acid has neuroprotective effects. The association between uric acid levels and dementia risk was reported by previous studies. However, recently published studies showed that the relationship between uric acid and dementia risk might be heterogeneous in dementia subtypes.
UNASSIGNED: This study aimed to clarify the relationship between hyperuricemia (or gout) and dementia.
UNASSIGNED: The PubMed and Web of Science databases were systematically searched up to April 2024 to identify relevant studies. A meta-analysis was conducted using hazard ratios (HR) or odds ratios (OR) and 95% confidence interval (CI) as pooled indicators. Heterogeneity between the studies was examined using Cochran\'s Q statistic and I2 statistic. Subgroup analyses were conducted for gender and age. Stratification analysis, sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Publication bias was assessed by funnel plot and Egger\'s test.
UNASSIGNED: A total of 11 studies met the inclusion criteria including 2,928,152 participants were abstracted. Hyperuricemia (or gout) did not reduce the overall risk of dementia (OR/HR = 0.92, 95% CI: 0.81-1.05) and vascular dementia (OR/HR = 0.74, 95% CI: 0.53-1.05), but may have a protective effect against Alzheimer\'s disease (OR/HR = 0.82, 95% CI: 0.70-0.96). Subgroup analysis showed that a lower risk of dementia was observed in men (OR/HR = 0.83, 95% CI: 0.77-0.90) and patients whose age under 65 (OR/HR = 0.83, 95% CI: 0.72-0.95).
UNASSIGNED: Patients with gout or hyperuricemia have a low risk of Alzheimer\'s disease.

BACKGROUND: Observational studies have suggested a correlation between hyperuricemia and pulmonary arterial hypertension (PAH), yet the causal relationship remains uncertain. We aimed to establish this link using Mendelian Randomization (MR) methods.
OBJECTIVE: Based on publicly accessible data, our study employs MR to determine the causal relationship between uric acid (UA) and PAH.
METHODS: MR analysis was conducted among individuals of European descent. Genetic instruments linked to UA (p-value < 5 × 10-8) were extracted from the Chronic Kidney Disease Genetic Consortium and genome-wide association study databases. PAH risk genetic associations were sourced separately. We employed four MR methods (MR-Egger, weighted median, inverse variance weighted, and weighted mode) with selected instrumental variables to assess the causal association between UA and PAH. MR-PRESSO was used to evaluate pleiotropy and outlier Single Nucleotide Polymorphisms (SNPs), while Cochran\'s Q test and funnel plot assessed SNP heterogeneity. Leave-one-out analysis examined SNP impacts on causal assessment.
RESULTS: Two-sample MR analysis revealed a positive, causal relationship between UA levels and PAH.
CONCLUSIONS: Our MR analysis provides robust evidence of a causal link between serum UA and PAH, suggesting UA\'s potential as a biomarker and therapeutic target for PAH.

OBJECTIVE: To analyze the function of the left heart in patients with different courses of gout, the independent influencing factors for left heart functional changes, and interactions between left atrial and left ventricular functions.
METHODS: Patients with gout (n = 171) were selected; 87 patients with a disease course <10 years were included in Group I, and 84 patients with a disease course ≥10 years were included in Group II. Ninety-four healthy volunteers comprised the control group.
RESULTS: The intergroup differences in cardiac strain parameters were statistically significant (p < .05). Moreover, the differences gradually declined with disease progression. Multivariate logistic regression analysis showed that uric acid was an independent predictor of decreased left ventricular global longitudinal strain (LVGLS). Moreover, LVGLS had a positive effect on the left atrial systolic rate (LASr) and the left atrial systolic contraction time (LASct) but no interaction with the left atrial systolic contraction duration (LAScd).
CONCLUSIONS: The course of the disease significantly affected the function of the left heart in gout patients, and uric acid was observed to be an independent predictor of decreased LVGLS in gout patients.

BACKGROUND: The pathogenic causes of primary gout include urate overproduction and/or renal or extra-renal urate underexcretion. The aim of this study was to evaluate the association of gout subtypes with the response to low-purine diet (LPD).
METHODS: This is a single-center prospective clinical study. Gout patients visiting from 2019 to 2022, from Shandong Gout Clinic Center at the Affiliated Hospital of Qingdao University, China, assigned to three groups according to clinical subtypes, were enrolled and all treated with 2-week low-purine diet. General characteristics, serum uric acid (sUA) and other clinical biochemical variables before and after the diet were evaluated.
RESULTS: A total of 626 gout patients (age 41.20 ± 13.41 years, male 98.0%) were included. Of these, 69 (11.0%) were overproduction type, 428 (68.37%) were underexcretion type, and 129 (20.61%) were combined type. Overall, there was a substantial decrease in sUA after a 2-week LPD (p < 0.001). In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum triglycerides (TG), serum total cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) levels were lower than those at baseline (p < 0.05). On the other hand, there were significant differences in the reduction of sUA among different types, the rank order being overproduction type (- 88.81 ± 63.01 μmol/L) > combined type (- 65.22 ± 44.13 μmol/L) > underexcretion type (- 57.32 ± 61.19 μmol/L). After adjusting for age, BMI and baseline sUA and eGFR, there were still significant differences in the decline of serum uric acid among different types. Higher baseline sUA (95%CI - 0.285, - 0.191; p < 0.001) and BUN (95%CI - 6.751, - 0.602; p < 0.001) were correlated with greater decrease of sUA.
CONCLUSIONS: Our findings support the protective role of low-purine diet on sUA levels in gout patients, especially overproduction type. Furthermore, LPD could exert a beneficial effect on gout patients\' blood pressure, BMI, blood lipid, BUN and Scr levels. Trial registration Registered with ChiCTR, No. ChiCTR1900022981 at 06/05/2019.

The metabolic disorders in the purine degradation pathway have proven to be closely associated with several human diseases. However, the etiology is not yet fully understood. Profile assay of purine intermediates and uric acid involved in the metabolic pathway can provide additional insight into the nature and severity of related diseases. Purine metabolites are endogenous chemicals with high hydrophilicity, polarity, and similar structures, thus there is a great need for a specific method to quantify them directly in biological fluids with a short running time. Herein, eight purine degradation pathway metabolites, including xanthine, hypoxanthine, guanine, xanthosine, inosine, guanosine, adenosine and uric acid, in human plasma were quantitatively measured using hydrophilic interaction chromatography-tandem high-resolution mass spectrometry (HILIC-HRMS) in a short running time of 10 min. The method was systematically validated for specificity, linearity of the calibration curve, the limit of detection, the limit of quantification, the lower limit of quantification, precision, accuracy, extraction recovery, matrix effect, and stability. The results showed that the method was linear (R2 > 0.99), accurate (the intra- and inter-day recoveries of all analytes ranged from 90.0 % to 110.0 %), and precise (the intra- and inter-day precisions were less than 6.7 % and 8.9 %, respectively) with the lower limits of quantification ranging from 3 to 10,000 ng/mL. The extraction recoveries and matrix effects were repeatable and stable. All the analytes were stable in the autosampler and could be subject to three freeze-thaw cycles. The developed method was ultimately applied to 100 plasma specimens from healthy individuals. The results showed that the concentrations of different purine metabolites varied dramatically in plasma specimens. Diet and body mass index (BMI) were the most significant factors determining purine levels, followed by drinking and sex. Age, smoking and bedtime showed a very weak correlation with purine metabolism. The findings of the present work reveal the characteristics of purine metabolism in human plasma under non-pathological conditions. The results also highlight the factors that can cause changes in purine metabolism, which are useful in developing effective treatment strategies for metabolic disorders of purines, particularly for those caused by lifestyle factors.

Monosodium urate (MSU) crystallisation deposited in local tissues and organs induce inflammatory reactions, resulting in diseases such as gout. MSU has been recognized as a common and prevalent pathology in various clinical conditions. In this study, we investigated the role of MSU in the pathogenesis of diabetic kidney disease (DKD). We induced renal injury in diabetic kidney disease mice using streptozotocin (STZ) and assessed renal histopathological damage using Masson\'s trichrome staining and Collagen III immunofluorescence staining. We measured the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and uric acid (UA) using ELISA. Protein expression levels of NLRP3, p-NF-κB, SHP2, p-STAT3, and p-ERK1/2 were analyzed by Western blot. To further investigate the role of MSU in diabetic kidney disease, we conducted in vitro experiments. In our in vivo experiments, we found that compared to the Model group, there was a significant increase in interstitial fibrosis in the kidneys of mice after treatment with MSU, accompanied by elevated levels of MDA, SOD, and UA. Furthermore, the protein expression of NLRP3, p-NF-NB, SHP2, p-STAT3, and p-ERK1/2 was upregulated. In our subsequent studies on mouse fibroblasts (L929 cells), we discovered that high glucose, MSU, and TGF-β could promote the expression of P22, GP91, NLRP3, NF-κB, p-NF-κB, p-SHP2, p-EGFR, p-STAT3, and Collagen-III proteins. Additionally, we found that SHP2 could counteract the upregulation trend induced by MSU on the expression of p-SHP2, p-EGFR, p-STAT3, and Collagen-III proteins, and inhibitors YQ128, NAC, and Cetuximab exhibited similar effects. Furthermore, immunofluorescence results indicated that SHP2 could inhibit the expression of the fibrosis marker α-SMA in L929 cells. These findings suggest that MSU can promote renal fibroblast SHP2 expression, induce oxidative stress, activate the NLRP3/NF-κB pathway, and enhance diabetic kidney disease fibroblast proliferation through the TGFβ/STAT3/ERK1/2 signaling pathway, leading to renal fibrosis.

We introduce the FlexoSERS sensor, which is notable for its high stretchability, sensitivity, and patternability. Featuring a hierarchically oriented jellyfish-like architecture constructed from stretchable gold nanowires, this sensor provides an ultrasensitive SERS signal even under 50% strain, with an enhancement factor (EF) of 3.3 × 1010. Impressively, this heightened performance remains consistently robust across 2,500 stretch-release cycles. The integration of nanowires with 3D-printed hydrogel enables a customizable FlexoSERS sensor, facilitating localized sweat collection and detection. The FlexoSERS sensor successfully detects and quantifies uric acid (UA) in both artificial and human sweat and functions as a pH sensor with repeatability and sensitivity across a pH range of 4.2-7.8, enabling real-time sweat monitoring during exercise. In summary, the rational architectural design, scalable fabrication process, and hydrogel integration collectively position this nanowire-based FlexoSERS sensor as a highly promising platform for customizable wearable sweat diagnostics.

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The disease can recur frequently and tends to form tophus in the joints. Current therapeutic drugs for the acute phase of GA have many side effects and limitations, are unable to prevent recurrent GA attacks and tophus formation, and overall efficacy is unsatisfactory. Therefore, we need to advance research on the microscopic mechanism of GA and seek safer and more effective drugs through relevant targets to block the GA disease process. Current research shows that the pathogenesis of GA is closely related to NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, and Ferroptosis. However, after synthesizing and sorting out the above mechanisms, it is found that the presence of ROS is throughout almost the entire spectrum of micro-mechanisms of the gout disease process, which combines multiple immune responses to form a large network diagram of complex and tight connections involved in the GA disease process. Current studies have shown that inflammation, oxidative stress, cell necrosis, and pathological signs of GA in GA joint tissues can be effectively suppressed by modulating ROS network-related targets. In this article, on the one hand, we investigated the generative mechanism of ROS network generation and its association with GA. On the other hand, we explored the potential of related targets for the treatment of gout and the prevention of tophus formation, which can provide effective reference ideas for the development of highly effective drugs for the treatment of GA.

OBJECTIVE: Our aim was to explore the relationship between serum uric acid (UA) levels in early pregnancy and the development of gestational diabetes mellitus (GDM), and to further explore whether there is a causal relationship.
METHODS: 684 pregnant women with GDM and 1162 pregnant women without GDM participated in this study. 311 pregnant women with GDM and 311 matched controls were enrolled in a 1:1 case-control study. We used conditional logistic regression to explore the relationship between UA levels and the risk of developing GDM. The causal relationship between the two was examined by two-sample Mendelian randomization (MR) analysis.
RESULTS: In the 1:1 matched population, the odds ratio (OR) of developing GDM compared with the extreme tertiles of UA levels was 1.967 (95% confidence interval [CI]: 1.475-2.625; P < 0.001). Restricted cubic spline analyses showed a linear relationship between UA and GDM when UA exceeded 222 µmol/L. GDM and UA levels maintained a statistically significant positive correlation in different stratified regression analyses (P < 0.001). However, no evidence of a causal relationship between uric acid and GDM was found by MR analyses with an OR of 1.06 (95% CI: 0.91-1.25) per unit increase in UA.
CONCLUSIONS: There is a positive correlation between UA levels in early pregnancy and the subsequent risk of developing GDM. However, no genetic evidence was found to support a cause-effect relationship between UA and GDM.