BACKGROUND:Little is known about the associations between long-term patterns of sleep and frailty and their impact on cardiovascular disease risk. We aimed to delineate trajectories of nighttime sleep duration and frailty, compare baseline characteristics across trajectory groups, and evaluate their independent and joint associations with cardiovascular disease (CVD) risk. METHODS:Trajectories of sleep duration and frailty index (FI) were modeled using three biennial waves (2011-2015) of the China Health and Retirement Longitudinal Study (CHARLS). Group-based and dual trajectory modeling identified distinct patterns. Baseline characteristics across trajectories were examined using multinomial logistic regression. Cox proportional hazards models estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for CVD events occurring during 2015-2018 follow-up. RESULTS:Among 6972 participants, four sleep trajectories and three frailty trajectories were identified. Compared with the stable-8-hours sleep trajectory, the stable-5-hours group had higher risks of CVD (HR: 1.33, 95 % CI: 1.05-1.68) and heart disease (HR: 1.42, 95 % CI: 1.07-1.88), significant only for women in sex-stratified analyses. Stable pre-frail and frail trajectories were linked to elevated risks of CVD (HR: 1.92, 95 % CI: 1.45-2.55; HR: 3.70, 95 % CI: 2.63-5.21) and heart disease (HR: 2.28, 95 % CI: 1.60-3.24; HR: 4.61, 95 % CI: 3.03-7.00) in both sexes. Dual-trajectory analyses revealed co-development patterns of sleep and frailty, with the highest CVD risk (HR: 3.04, 95 % CI: 1.88-4.91) observed among individuals with both stable pre-frail/frail and stable-5-hours trajectories. CONCLUSION:Sleep duration and frailty trajectories are interrelated over time and jointly influence CVD risk. Monitoring their long-term patterns may improve the precision of CVD prevention.

The impact of specific comorbidity combinations on the risk and severity of acute kidney injury (AKI) in older critically ill patients remains unclear. This study aimed to identify comorbidity phenotypes using latent class analysis (LCA) and quantify their associations with hospital-acquired AKI. We conducted a retrospective study using the MIMIC-IV database on first-time ICU patients (> 65 years) with a length of stay ≥ 48 h. Patients with baseline chronic kidney disease (CKD) or early-onset AKI were excluded. LCA was applied to baseline chronic conditions to identify distinct comorbidity phenotypes. Subsequently, we employed multivariable Cox proportional hazards models to evaluate AKI incidence, and logistic regression to assess AKI severity (KDIGO Stage ≥ 2), adjusting for potential confounders. Of 5,721 eligible patients, 2,202 (38.5

Viral myocarditis (VMC) is a prevalent inflammatory cardiac condition, characterized by highly variable clinical manifestations that present significant challenges for early diagnosis and the development of personalized treatment strategies. Consequently, there is an urgent need to develop novel biomarkers and targeted therapeutic approaches to enhance its clinical management. Circulating microRNAs (miRNAs) have emerged as promising candidates for disease diagnosis and treatment due to their stability as intercellular communication molecules and resistance to nuclease degradation. Their significance in various disease contexts has garnered considerable research attention. Recent advancements in high-throughput sequencing technologies, coupled with deep learning and the integration of artificial intelligence (AI) into RNA/protein structure prediction, have improved our understanding of the roles of regulatory networks involving circulating microRNAs in the pathogenesis of viral myocarditis. This systematic review covers recent evidence for the clinical applicability and limitations of the use of circulating miRNAs as specific diagnostic and therapeutic targets for viral myocarditis. It was performed with the aim of establishing a theoretical foundation and strategic framework to improve the precision of this condition's diagnosis and treatment.

Objective To test associations of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 ( CDKAL1 ) gene variants with the risk of adverse pregnancy outcome in Chinese women and whether the association was mediated by occurrence of gestational diabetes mellitus. Methods We organized a 1:1 age-matched study nested within a prospective cohort of pregnant women (207 pairs) established in urban Tianjin. Adverse pregnancy outcome was defined as a composite outcome of preterm birth, low birth weight or macrosomia. Logistic regression analyses were used to estimate associations of CDKAL1 gene variants with adverse pregnancy outcome and its components. The CDKAL1 genetic marker was defined as encompassing any of the identified susceptibility variants for adverse pregnancy outcome. Results The CDKAL1 genetic marker was associated with the risk of adverse pregnancy outcome (OR: 2.51, 95%CI: 1.47, 4.28), low birth weight (OR: 19.80, 95%CI: 2.15, 182) and macrosomia (OR: 2.40, 95%CI: 1.17, 4.93), but not with preterm birth ( P = 0.105) after adjusting for traditional risk factors. Further adjusting for gestational diabetes mellitus, the CDKAL1 genetic marker remained significantly associated with adverse pregnancy outcome, and the OR (95%CI) was 2.52 (1.48, 4.30). Conclusion The maternal CDKAL1 gene variants were associated with increased risk of adverse pregnancy outcome, low birth weight and macrosomia, independent of gestational diabetes mellitus. CDKAL1 gene might be a useful marker for identification of individuals at a particularly high risk of adverse pregnancy outcome in early pregnancy.

The study aimed to investigate the separate, interactive, and combined effects of depression and physical multimorbidity on all-cause mortality using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), and multimorbidity was defined as the presence of ≥ 2 chronic conditions. Cox proportional hazards models were used to assess these associations. During a median follow-up of 8.3 years (interquartile range, 5.4-11.4), 3,005 deaths occurred. After adjusting for potential confounders and multimorbidity, each one-point increase in depression score was associated with a 3% higher risk of mortality (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02-1.04). Compared to those without depressive symptoms, mild and moderate to severe symptoms were linked to a 27% (HR: 1.27, 95% CI: 1.11-1.47) and 37% (HR: 1.37, 95% CI: 1.17-1.61) higher mortality risk, respectively. However, among women, only moderate to severe depression was significantly associated with increased mortality (HR: 1.50, 95% CI: 1.19-1.89). After adjusting for potential confounders and depression, multimorbidity was associated with a 64% higher mortality risk (HR: 1.64, 95% CI: 1.46-1.86). No significant interaction between depression and multimorbidity was found. Joint analysis showed that among participants without multimorbidity, moderate to severe depressive symptoms increased mortality risk (HR: 1.54, 95% CI: 1.09-2.17). In those with multimorbidity, risk increased with depression severity, peaking at HR: 2.22 (95% CI: 1.85-2.65). These findings highlight depression and multimorbidity as independent mortality risk factors, with their combined presence further amplifying this risk.

OBJECTIVES:The relationship between actigraphy-derived sleep parameters, day-to-day deviations in sleep parameters, and metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of nonalcoholic fatty liver disease (NAFLD), remains unclear. We aimed to explore the associations of sleep duration, midpoint, variability and irregularity with MASLD risk. METHODS:We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Sleep duration and midpoint were estimated from 4 to 7 days of 24-hour actigraphy measurements. Sleep duration and midpoint standard deviation were used as indicators of sleep variability and irregularity, respectively. MASLD was diagnosed according to the multi-society Delphi consensus. Hepatic steatosis was defined as fatty liver index ≥ 60. Multivariable weighted logistic regression models were used to explore correlations and perform subgroup analyses. RESULTS:A total of 5,316 participants were included, of whom 2,339 had MASLD. After adjusting for socio-demographic characteristics, lifestyle factors, and depression, compared to sleep variability < 60 minutes, the odds ratio (OR) [95% confidence interval (CI)] was 1.13 (0.96-1.34) for 60-90 minutes, and 1.17 (1.00-1.38) for > 90 minutes (P for trend = .034). After further adjustment for other sleep variables, short sleep duration (<7 hours) was associated with a 24% higher risk of MASLD (OR: 1.24, 95% CI: 1.01-1.53); compared to sleep irregularity < 38 minutes, OR (95% CI) was 1.27 (1.02-1.59) for 38-61 minutes and 1.43 (1.24-1.65) for > 61 minutes (P for trend = .003). CONCLUSION:In addition to sleep duration, sleep irregularity may need to be considered in the prevention of MASLD.

BACKGROUND Several studies have suggested a close link between depression, overweight, and new-onset diabetes, particularly among middle-aged and older populations; however, the causal associations remain poorly understood. AIM To investigate the role of overweight in mediating the association between depression and new-onset diabetes in middle-aged and older populations. METHODS Data of 9426 individuals aged ≥ 50 years from the 1998-2016 Health and Retirement Study database were analyzed. Weighted logistic regression was employed to obtain odds ratios (ORs) and 95% confidence intervals (95%CIs) for depression and new-onset diabetes in the middle-aged and older populations. Mediation analysis and the Sobel test were used to test the mediating effects of overweight between depression and the risk of new-onset diabetes. RESULTS New-onset diabetes was identified in 23.6% of the study population. Depression was significantly associated with new-onset diabetes (OR: 1.18, 95%CI: 1.03-1.35, P value: 0.014). Further adjustment for overweight attenuated the effect of depression on new-onset diabetes to 1.14 (95%CI: 1.00-1.30, P = 0.053), with a significant mediating effect (P of Sobel test = 0.003). The mediation analysis demonstrated that overweight accounted for 61% in depression for the risk of new-onset diabetes, with overweight having a partially mediating role in the depression-to-diabetes pathway. CONCLUSION New-onset diabetes was not necessarily a direct complication of depression; rather, depression led to behaviors that increase the risk of overweight and, consequently, new-onset diabetes.

ABSTRACT Objective To estimate the disease burden of type 2 diabetes (T2D) in early‐onset (age < 40) and late‐onset (age ≥ 40) in the U.S. Methods Data obtained from the National Health and Nutrition Examination Survey 2003–2018. Prevalence, number, and disability‐adjusted life years (DALYs) in early‐onset and late‐onset T2D were assessed. Results There was a clear and steady upward trend in early‐onset T2D, although the prevalence and number of late‐onset T2D were higher than early‐onset. The average loss of DALYs per capita (DALYs/per) in the early‐onset T2D was higher than that in the late‐onset. DALYs/per is higher in males than females in both early‐ and late‐onset T2D groups. People living at or below the poverty line and those with education of high school and below had a higher DALYs/per of early‐onset T2D. Among individuals with early‐onset T2D, the DALYs/per loss was higher in the non‐obesity group. Conclusion There was a clear upward trend in the prevalence of early‐onset T2D, and the loss of DALYs/per in early‐onset T2D was higher than that in late‐onset T2D. The attribution risk factors, like sex, education levels, income levels, and body mass index, for the burden of early‐onset T2D varied, and measures need to be taken to target different populations.

Education, as a proxy for cognitive reserves, has been linked to dementia; however, the association between education attainment and brain health remains unclear. We aim to investigate the association between education attainment and neuroimaging based brain-predicted age difference (BPAD, the difference between brain age and chronological age). The study included 32,322 chronic neurological disease-free participants (mean age 54.74 ± 7.49 years, 46.58% female) who underwent brain MRI scans 9+ years after baseline. Years of education were self-reported and categorized as low (7 and 10 years), medium (13, 15, and 19 years), and high (20 years) according to the International Standard Classification of Education. BPAD was predicted based on 1,079 multimodal imaging-derived phenotypes (including structural and functional MRI) by a LASSO machine learning model. Alzheimer's disease-related polygenic risk score (PRS AD ) was tertiled as low, moderate and high. Data were analyzed using linear regressions. At baseline, 6,332 (19.59%), 10,872 (33.64%), and 15,118 (46.77%) participants had low, medium, and high education, separately. Compared to low education, high education (β [95% CI]: -0.230 [-0.392, -0.067]) was related to more negative BPAD. In joint-effect analysis, the β (95% CI) of BPAD was -0.542 (-0.796, -0.289) among participants with high education and low-to-moderate PRS AD , compared to those with low education and high PRS AD . High education attainment was associated with more negative BPAD, particularly among people with a low-to-moderate genetic susceptibility for dementia.

Background Social app recruiting-based and peer-led testing strategies have been proven effective in increasing human immunodeficiency virus (HIV) testing among men who have sex with men (MSM), though their combination remains underevaluated. We aimed to assess the efficiency of a combined strategy named "standardly trained peer volunteer-led, social app recruiting-based HIV testing strategy using rapid testing kits" (SPARK).Methods Between March 2020 and December 2021, 177 trained peer volunteers tested 7256 eligible MSM testers. Volunteers primarily recruited testers to undergo HIV testing and counseling in social apps. Volunteers tested testers with HIV rapid antibody tests and interviewed testers while waiting for the results. Moreover, HIV testing data from other testing strategies, both pre- and postimplementation of SPARK, were collected to evaluate the capacity of SPARK to increase HIV testing.Results During this study, MSM testers underwent 10 441 HIV tests; HIV testing volume increased 3-fold from 2020 to 2021. On average, each volunteer recruited 40.99 testers and facilitated 58.99 HIV tests. After SPARK implementation, HIV tests in 2021 increased 1-fold compared with those in 2019; especially for rural MSM testers, the number of HIV tests performed in 2020 and 2021 increased to 2.86 and 5.85 times, respectively, that in 2019. In spatial analysis, most testers sought geographical proximity volunteers for testing; similarly, most testers recruited were from volunteers' own or nearby districts. More than 60% of HIV tests were performed outside of working hours on weekdays, regardless of whether the testers came from urban, periurban, or rural areas.Conclusions SPARK, an MSM-friendly, geographically accessible, and time-flexible testing strategy, has the potential to promote HIV testing among MSM. SPARK, a social app recruiting-based and peer-led testing strategy, is MSM-friendly, time-flexible, and geographically accessible, offering an alternative to existing HIV testing strategies. These new findings provide a novel HIV testing strategy for MSM in areas with social network infrastructure but limited testing resources.

BACKGROUND AND OBJECTIVES:Cardiovascular health (CVH) has been associated with cognitive decline and dementia, but the extent to which CVH affects brain health remains unclear. We investigated the association of CVH, assessed using Life's Essential 8 (LE8), with neuroimaging-based brain age and brain-predicted age difference (brain-PAD). METHODS:This longitudinal community-based study was based on UK Biobank participants aged 40-69 years who were free from dementia and other neurologic diseases at baseline. LE8 score at baseline was assessed with 8 measures and tertiled as low, moderate, and high CVH. Structural and functional brain MRI scans were performed approximately 9 years after baseline, and 1,079 measures from 6 neuroimaging modalities were used to model brain age. A Least Absolute Shrinkage and Selection Operator regression model was trained in 4,355 healthy participants and then used to calculate brain age and brain-PAD in the whole population. Data were analyzed using linear regression models. RESULTS:The study included 32,646 participants (mean age at baseline 54.74 years; 53.44% female; mean LE8 score: 71.90). In multivariable-adjusted linear regression, higher LE8 score was associated with younger brain age (β [95% CI] -0.037 [-0.043 to -0.031]) and more negative brain-PAD (β [95% CI] -0.043 [-0.048 to -0.038]) (brain looks younger for chronological age). Compared with high CVH, low/moderate CVH was associated with older brain age (β [95% CI] 1.030 [0.852-1.208]/0.475 [0.303-0.647]) and increased brain-PAD (β [95% CI] 1.193 [1.029-1.357]/0.528 [0.370-0.686]). The associations between low CVH and older brain age/brain-PAD remained similar and significant in both middle-aged (β [95% CI] 1.199 [0.992-1.405]/1.351 [1.159-1.542]) and older adults (β [95% CI] 0.764 [0.417-1.110]/0.948 [0.632-1.263]). DISCUSSION:Low CVH is associated with older brain age and greater brain-PAD, even among middle-aged adults. Our findings suggest that optimizing CVH could support brain health. The main limitation of our study is that the study sample was healthier than the general population, thus caution is required when generalizing our findings to other populations.

Abstract Background Several studies have demonstrated the population-level effectiveness of oral PrEP in reducing the risk of HIV infection. However, oral PrEP utilization among MSM in China remains below 1%. While existing literature has primarily focused on oral PrEP preference and willingness, there is limited exploration of the underlying factors contributing to oral PrEP cessation in China. This study aims to fill this gap by investigating the factors associated with oral PrEP cessation among MSM in China. Methods Assisted by MSM community organizations, we collected 6,535 electronic questionnaires from 31 regions across China, excluding Taiwan, Hong Kong, and Macau. The questionnaire focused on investigating MSM's awareness, willingness, usage, and cessation of oral PrEP. Additionally, 40 participants were randomly chosen for key informant interviews. These qualitative interviews aimed to explore the reasons influencing MSM discontinuing oral PrEP. Results We eventually enrolled 6535 participants. Among the 685 participants who had used oral PrEP, 19.70% (135/685) ceased oral PrEP. The results indicated that individuals spending > ¥1000 on a bottle of PrEP (aOR = 2.999, 95% CI: 1.886–4.771) were more likely to cease oral PrEP compared to those spending ≤ ¥1000. Conversely, individuals opting for on-demand PrEP (aOR = 0.307, 95% CI: 0.194–0.485) and those using both daily and on-demand PrEP (aOR = 0.114, 95% CI: 0.058–0.226) were less likely to cease PrEP compared to those using daily PrEP. The qualitative analysis uncovered eight themes influencing oral PrEP cessation: (i) High cost and low adherence; (ii) Sexual inactivity; (iii) Lack of knowledge about PrEP; (iv) Trust in current prevention strategies; (v) Poor quality of medical service and counseling; (vi) PrEP stigma; (vii) Partner and relationship factors; (viii) Access challenges. Conclusions The cessation of oral PrEP among MSM in China is associated with various factors, including the cost of oral PrEP medication, regimens, individual perception of HIV risk, stigma, and the quality of medical services. It is recommended to provide appropriate regimens for eligible MSM and develop tailored combinations of strategies to enhance PrEP awareness and acceptance among individuals, medical staff, and the MSM community. The findings from this study can support the refinement of HIV interventions among MSM in China, contributing to efforts to reduce the burden of HIV in this population.

OBJECTIVE:Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of non-apoptotic cell death process. Previous studies have demonstrated that ferroptosis participates in the development of inflammatory arthritis. However, the role of ferroptosis in rheumatoid arthritis (RA) inflammatory hypoxic joints remains unclear. This study sought to explore the underlying mechanism of ferroptosis on lipopolysaccharide (LPS)-induced RA fibroblast-like synoviocytes (FLSs).METHODS:FLSs, isolated from patients with RA, were treated with LPS and ferroptosis inducer (erastin and RSL-3), and ferroptosis inhibitor (Fer-1 and DFO), respectively. The cell viability was measured by CCK-8. The cell death was detected by flow cytometer. The proteins level were tested by Western blot. The cytosolic ROS and lipid peroxidation were determined using DCFH-DA and C11-BODIPY581/591 fluorescence probes, respectively. The small interfering RNA (siRNA) was used to knock down related proteins. The levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), iron, inflammatory cytokines (IL6 and IL8), and LDH were analyzed by commercial kits.RESULTS:Ferroptosis was activated by LPS in RA FLS with increased cellular damage, ROS and lipid peroxidation, intracellular Fe and IL8, which can be further amplified by ferroptosis inducer (erastin and RSL-3) and inhibited by ferroptosis inhibitor (Fer-1 and DFO). Mechanistically, LPS triggered ferroptosis via NCOA4-mediated ferritinophagy in RA FLSs, and knockdown of NCOA4 strikingly prevent the process of ferroptosis. Intriguingly, LPS-induced RA FLSs became insensitive to ferroptosis and NCOA4-mediated ferritinophagy under hypoxia compared with normoxia. Knockdown of HIF-1α reverted ferroptosis and ferritinophagy evoking by LPS-induced RA FLSs inflammation under hypoxia. In addition, low dose of auranofin (AUR) induced re-sensitization of ferroptosis and ferritinophagy through inhibiting the expression of HIF-1α under hypoxia.CONCLUSIONS:NCOA4-mediated ferritinophagy was a key driver of ferroptosis in inflammatory RA FLSs. The suppression of NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in LPS-induced inflammation under hypoxia. Targeting HIF-1α/NCOA4 and ferroptosis could be an effective and valuable therapeutic strategy for synovium hyperplasia in the patients with RA.

Abstract Background Osteoarthritis (OA) is a common joint disease that may affect brain function via a joint-brain axis, but its causal impact on brain cortical structures is unclear. Method We used Mendelian randomization (MR), a method that leverages genetic variants as natural experiments, to examine the effects of OA, including knee and hip OA, on cortical surface area (SA) and thickness (TH) of the whole brain and 34 functional regions. We used summary statistics from large-scale genome-wide association studies (GWAS) of OA and brain cortical structures in individuals of European ancestry. Result We found that overall OA was causally associated with reduced SA of the isthmus cingulate (beta: -296.2, 95% CI: -439.1, -153.3, P = 4.82e-05), a brain region involved in mood, memory, and spatial orientation. This suggests that OA may influence neuropsychiatric disorders in OA patients. We also detected several suggestive associations between OA and other brain regions. Conclusion Our study reveals a novel causal link between OA and brain cortical structures, with implications for understanding and treating cognitive impairment and other disorders in OA patients. Our findings also highlight the importance of considering the joint-brain axis in clinical practice and future research.

Abstract Introduction Few studies focused on the Pre-Exposure Prophylaxis (PrEP) -related aspects, and the applicability of prior evidence to young men who have sex with men (YMSM) students was unknown. This study aimed to assess the awareness, willingness, uptake, and adherence (AWUA) to PrEP among YMSM students in China and to explore the associated factors with these stages. Methods A cross-sectional survey with a sizable sample of 1151 was conducted among YMSM students aged 16 and above, who self-identified as men who have sex with men(MSM) and resided in mainland China between October 20 and December 20, 2021. The chi-square test and Fisher’s exact test were used for univariate analysis, followed by multivariable logistic regression analysis of influencing factors at all levels. Results According to the cascade analysis approach, 88.71% of the participants were aware of PrEP, among which 66.7% expressed willingness to use it. Among those who were willing to use PrEP, only 13.80% took it, and of those who took it, 44.68% adhered to it. The students taking PrEP were those with higher education (OR = 4.239, 95% CI: 1.334–13.467), residence in pilot cities (OR = 2.791, 95% CI: 1.498–5.198), residence in high-risk areas (OR = 5.082, 95% CI: 2.224–11.612), engagement in multi-person sexual behavior (OR = 2.186, 95% CI: 1.236–3.867), and substance use (OR = 1.908, 95% CI: 1.167–3.118). Furtherly, students with higher adherence to PrEP were likely to have receptive sexual behaviors (OR = 8.702, 95% CI: 2.070-36.592), absence of substance use (OR = 4.468, 95% CI: 1.371–14.561), and uptake of PrEP through daily oral route. (OR = 7.065, 95% CI: 1.699–29.371). Conclusion YMSM students exhibit distinct patterns of “high awareness, low willingness, low uptake, and low adherence” to PrEP. Strategies for reduction in the acquisition of HIV prioritizing the current features of utilizing PrEP were urgently warranted.

Men who have sex with men (MSM) are at a high risk of HIV infection and should be offered effective preventive measures, such as pre-exposure prophylaxis (PrEP). However, PrEP uptake among eligible MSM was not as high as desired. Diverse research findings on how risky sexual behaviors affect PrEP uptake highlight the necessity for a comprehensive investigation. Understanding the interconnectedness of different sexual behaviors is crucial for evaluating their impact on PrEP uptake among eligible MSM.Using a proportional sampling method, we recruited 5877 MSM aged 16 years and above in mainland China according to PrEP eligibility criteria. Through latent class analysis (LCA), three distinct sexual behavior patterns were identified among eligible MSM. Demographic variances and PrEP uptake among the three distinct sexual behavior patterns were examined using chi-squared tests and multinomial logistic regression.LCA revealed three patterns: low-risk (4,815 MSM), medium-risk (516 MSM), and high-risk (546 MSM). MSM aged 25 years or older with a monthly income of ≥¥8,000 were more likely to be in the medium-risk group. Those from areas with high HIV prevalence and engaging as ''top'' in anal sex were more likely to be in the medium- and high-risk groups. The medium- and high-risk groups had a higher willingness, uptake, and adherence rates for PrEP than the low-risk group.LCA is effective in identifying diverse sexual behavior patterns among MSM, aiding targeted interventions to enhance PrEP uptake. Addressing demographic variations and tailoring interventions for specific risk groups are crucial for promoting PrEP dissemination and reducing HIV infection risk in eligible MSM.

Background Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis. Methods The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout. Results We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A. Conclusion According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.

ObjectivesExposure to air pollution has been linked to an increased risk of premature mortality. However, the acute effects of air pollution on the risk of non-accidental mortality have not been extensively researched in developing countries, and the findings thus far have been inconsistent. Therefore, this study aimed to examine the association between short-term exposure to six pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and non-accidental mortality in Beijing, China.MethodsDaily data on non-accidental deaths were gathered from 1 January 2017 to 31 December 2018. Air pollution data for the same period were collected from 35 fixed-site air quality monitoring stations in Beijing. Generalized additive models (GAM) based on Poisson regression were used to investigate the association between non-accidental mortality in emergency department visits and the daily average levels of air pollutants.ResultsThere were 8,676 non-accidental deaths recorded during 2017–2018. After sensitivity analysis, short-term exposure to air pollutants, particularly gaseous pollutants, was linked to non-accidental mortality. Specifically, for every 10 μg/m3 increase (5 μg/m3 in SO2, 0.5 mg/m3 in CO) of SO2 (lag 04), NO2 (lag 04), O3 (lag 05), and CO (lag 04), the relative risk (RR) values were 1.054 (95% CI: 1.009, 1.100), 1.038 (95% CI: 1.013, 1.063), 1.032 (95% CI: 1.011, 1.054), and 1.034 (95% CI: 1.004, 1.066), respectively. In terms of causes of death, short-term exposure to NO2, SO2, and O3 increased the risk of circulatory mortality. Further stratified analysis revealed that the stronger associations were presented in females for O3 while in males for CO. People aged 65 and over were strongly associated with ambient air pollution.ConclusionsOur study showed that ambient air pollutants were associated with non-accidental mortality. Our findings suggested that efforts to control gaseous pollution should be stepped up, and vulnerable groups should be the focus of health protection education.