Background: Although integrase strand transfer inhibitor (INSTI)-based regimens are guideline-preferred, implementation in routine antiretroviral therapy (ART) programs remains gradual, and EFV-, NVP-, and PI-based regimens continue to contribute treatment exposure. Evidence is limited on long-term virological outcomes across ART anchor classes when regimen use changes over time and viral-load monitoring is clinically driven. Methods: We analyzed people living with HIV aged ≥15 years who initiated ART in Henan, China, during 2015-2024. ART class was categorized as EFV-, NVP-, INSTI-, or PI-based and assessed as initial and time-updated exposure. Outcomes were HIV RNA ≥200 copies/mL, HIV RNA ≥1000 copies/mL, and virological rebound after prior suppression. Cox models, IPTW MSMs, and joint IPTW-IIW MSMs were fitted, with joint IPTW-IIW MSMs prespecified as primary. Results: Among 44,746 participants, 8,399, 5,821, and 5,364 developed non-suppression, high-level viremia, and rebound, respectively. In primary joint MSMs, INSTI-based ART was associated with lower hazards across all outcomes in initial-regimen analyses (HRs, 0.56 [95% CI, 0.45-0.69], 0.42 [0.31-0.56], and 0.66 [0.50-0.87]) and time-updated analyses (0.54 [0.45-0.66], 0.40 [0.31-0.52], and 0.64 [0.51-0.81]). NVP-based ART was consistently associated with higher hazards. PI-based ART was also associated with higher hazards, particularly in time-updated analyses. Conclusions: During ART transition, INSTI-based regimens showed more favorable virological profiles, whereas NVP- and PI-based regimens were associated with higher virological risk. Accounting for both initial and changing regimen use, together with informative viral-load observation, improves real-world evaluation of regimen-class performance in care.

While air pollution may adversely affect acute upper respiratory infection (AURI), whether meteorological factors modify this effect rarely been studied. This study sought to examine the association of air pollution with the morbidity of AURI as well as the modification effects of temperature and relative humidity (RH). Daily AURI visits data were obtained from Zhengzhou university hospital from 2014 to 2019. Distributed lagged nonlinear model (DLNM) was used to assess the effect of air pollutants on AURI morbidity. The modification effects of temperature and RH on the association of air pollution with AURI morbidity was explored by DLNM with an interaction term of the cross-basis of air pollutants and the temperature or RH. During the study period, 87,186 college students sought medical care for AURI. The relative risk (RR) and 95

AIMS:This study aims to examine the effect of relative muscle strength (RMS) on the progression to diabetes or regression to normoglycemia in individuals with prediabetes. METHODS:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS), which followed 3250 individuals aged ≥45 years with prediabetes. RMS was calculated as the ratio of grip to appendicular skeletal muscle mass (ASM). Multinomial logistic regression was used to assess the association of RMS with subsequent glycemic transitions, including regression to normoglycemia, persistence of prediabetes, and progression to diabetes. Mediation analysis explored the role of inflammation and lipid profiles in this association. RESULTS:During the follow-up period, 1953 participants remained in the prediabetes stage, 698 reverted to normoglycemia, and 599 progressed to diabetes. Participants regressing to normoglycemia exhibited significantly higher RMS than those remaining prediabetic [M (IQR): 2.25 (1.85, 2.62) vs. 2.16 (1.78, 2.55)], whereas those who progressed to diabetes showed lower RMS [1.97 (1.61, 2.32)]. Compared to the low RMS group, the OR (95% CI) for the high RMS group was 0.49(0.38, 0.64). Mediation analysis showed that high-density lipoprotein (HDL), triglycerides (TG), and C-reactive protein (CRP) partially mediated the effect between RMS and prediabetes progression, accounting for 14.47%, 4.41%, and 0.21% of the overall effect, respectively. CONCLUSIONS:Higher RMS independently protects against prediabetes progression and may aid regression, mediated by HDL, TG, and CRP.

To investigate the association between atmospheric temperature and embryonic development and pregnancy outcomes in women undergoing IVF/ICSI, and to evaluate the interaction between temperature and PM2.5. This study included 3747 patients undergoing IVF/ICSI treatment at one tertiary hospital in Henan Province from January 2015 to August 2023. Daily mean temperature, relative humidity, and PM2.5 concentrations were sourced from publicly available datasets. Temperature exposure was evaluated across seven time windows, with average levels calculated for each. Outcome measures encompassed oocyte and embryo quality indicators and pregnancy outcomes. Compared with the reference temperature range, exposure to low temperature dTimes New Romanuring Period C (from the start of gonadotropin treatment to oocyte retrieval) was associated with − 2.95 (95

OBJECTIVES:To compare associations of antiretroviral therapy (ART) strategies with all-cause mortality and assess whether first opportunistic infection (OI) occurrence and time partly explain survival differences. METHODS:We analyzed 38,692 people with HIV in Henan Province (2015-2024). ART initiation timing and regimen were assessed, with early initiation defined as CD4+ T cell counts ≥500 cells/μL. Cox regression estimated associations with all-cause mortality and first OI. Multistate models characterized transitions to first OI and death, and time-to-event mediation analyses quantified the contribution of OI occurrence and time. RESULTS:During a median follow-up of 5.07 years, 2868 deaths occurred. Compared with late ART initiation, early initiation was associated with lower all-cause mortality (HR: 0.46; 95% CI: 0.41-0.52), and a lower transition hazard from OI to death (HR: 0.47; 95% CI: 0.27-0.81). Compared with PI-based regimens, INSTI- and NNRTI-based regimens showed lower observed all-cause mortality risks, with HRs (95% CI) of 0.51 (0.35-0.73) and 0.60 (0.50-0.72), respectively. At 5 years, early ART initiation and INSTI-based therapy were associated with absolute reductions in cumulative mortality risk of 8.51% and 4.76%, respectively, with residual disparity close to the total effect and a small shifting distribution effect (< 0.30%) attributable to first OI occurrence and time. CONCLUSIONS:Earlier ART initiation, especially at CD4+T cell counts ≥500 cells/μL, was associated with better survival. INSTI- and NNRTI-based regimens showed more favorable observed mortality outcomes than PI-based regimens. OI occurrence and time explained only a limited proportion of survival differences.

BACKGROUND/OBJECTIVES:To evaluate the associations between sedentary behavior and physical activity (PA) with biological aging and the effect on biological aging of replacing sedentary behavior with an equal amount of time spent on different PA. METHODS:A total of 301,603 U.K. adults (aged 38-73 years) were included. Sedentary behavior was quantified by summing up the time spent on watching TV, using computer, and driving every day. PA was quantified by the duration and frequency of light, moderate, and vigorous PA. Biological aging was estimated by PhenoAge algorithms based on clinical traits. Linear regression and isotemporal substitution model were used to test the relationships of sedentary behavior and PA with biological aging. RESULTS:Compared with individuals with sedentary behavior ≤3 hr/day, those with sedentary behavior of 3-5, 5-8, and >8 hr/day were associated with higher biological age acceleration, respectively. Consistently, PA was associated with lower biological age acceleration (p < .001). The isotemporal substitution model suggested that replacing sedentary behavior with PA (in hours per day) can delay biological age acceleration (light PA: β = -0.12, 95% CI [-0.14 to -0.09]; moderate PA: β = -0.22, 95% CI [-0.25 to -0.18]; vigorous PA: β = -0.21, 95% CI [-0.28 to -0.14). Multiplicative interactions were observed between sedentary behavior and all type of PA on biological age acceleration (p for interaction <.001). CONCLUSION:Based on UK Biobank cohort, sedentary behavior and lack of PA were associated with accelerated biological aging, while replacing sedentary behavior with PA was linked to slower biological aging. Significance/Implications: To delay biological aging, the population should replace sedentary behaviors with PA.

INTRODUCTION:To compare the mortality effects of dynamic antiretroviral therapy (ART) regimens among people with HIV (PWH), while accounting for time-varying CD 4+ T cell counts and HIV viral loads. METHODS:Leveraging data from 32 713 ART-naïve individuals (2015-2024) in Henan, China, we compared three approaches: baseline, time-fixed Cox model that classified participants by ART class at initiation, time-varying Cox model that updated ART class over follow-up; and marginal structural model (MSM) to address time-varying confounding. ART regimens were classified as nonnucleoside reverse transcriptase inhibitor (NNRTI)-, integrase strand transfer inhibitor (INSTI)-, or protease inhibitor (PI)-based regimens (reference: NNRTI). Outcomes included all-cause mortality and AIDS-related mortality. RESULTS:Effect estimates shifted from the baseline time-fixed model toward stronger protective associations after incorporating time-updated ART exposure and further adjusting for time-varying confounding. In the MSM, compared with NNRTI-based regimens, INSTI- and PI-based regimens were associated with lower all-cause mortality [INSTI: hazard ratio (HR) = 0.38, 95% confidence interval (CI): 0.29-0.49; PI: HR=0.69, 95% CI: 0.52-0.91] and lower AIDS-related mortality (INSTI: HR = 0.31, 95% CI: 0.17-0.57; PI: HR = 0.47, 95% CI: 0.25-0.89). Secondary exploratory cumulative exposure analyses yielded patterns broadly consistent with lower mortality for INSTI exposure, whereas estimates for PI exposure were closer to the null and should be interpreted cautiously. CONCLUSION:Accounting for time-updated ART exposure and time-varying confounding, INSTI-based regimens were associated with lower all-cause and AIDS-related mortality than NNRTI-based regimens. These findings underscore the need to account for dynamic ART exposure and time-varying confounding in observational comparative effectiveness studies of ART regimens.

OBJECTIVE:This study investigated the associations of intrinsic capacity, a multidomain measure of functional health, with the incidence and progression of ischemic heart disease, and the mediation of such associations by indices related to insulin resistance (IR). METHODS:We included 386,462 adults from the UK Biobank who were free of ischemic heart disease and its associated complications, including heart failure and arrhythmia, at baseline. Associations were estimated using Cox models, and multistate models for transitions. Mediation by IR-related indices was quantified in a counterfactual framework. RESULTS:Over a median 13.68 years of follow-up, 29,994 ischemic heart disease events occurred. Hazard ratios (95% confidence intervals) for ischemic heart disease were 1.15 (1.11-1.18), 1.38 (1.33-1.43), 1.68 (1.61-1.75), and 2.24 (2.12-2.37) for intrinsic capacity scores of 1, 2, 3, and ≥4 versus 0. Estimates from the multistate model for the transition from baseline to ischemic heart disease were consistent with the Cox results. Hazard ratios (95% confidence intervals) for transition from ischemic heart disease to death were 1.32 (1.14-1.53) for intrinsic capacity score 3 and 1.46 (1.21-1.74) for intrinsic capacity score ≥ 4, and 1.30 (1.09-1.56) from complications to death for intrinsic capacity score ≥ 4. IR-related indices accounted for 6.77-22.40% of the association between intrinsic capacity and ischemic heart disease, 5.38-24.24% for complications, and 2.22-10.04% for death. CONCLUSIONS:Lower intrinsic capacity was associated with higher risks of ischemic heart disease and its progression, partly through IR-related pathways, supporting metabolic dysfunction as a modifiable target for early risk stratification.

Atherosclerosis have been implicated in cardiovascular disease (CVD) risks, and whether frailty played a mediating role in this association was unclear. This study aimed to assess the associations of cumulative atherosclerosis index of plasma (CumAIP) exposure with incidence of CVD and evaluate the mediating role of frailty. The study analyzed data from the China Health and Retirement Longitudinal Study (CHARLS) cohort. Triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were extracted to calculate the CumAIP. Frailty was assessed using the frailty index (FI). CVD events were confirmed based on medical history. Cox proportional hazards, linear regression, and restricted cubic spline (RCS) models were employed, along with mediation analysis. Increased atherosclerosis was associated with increased risks of CVD. In the fully adjusted Cox model, compared to the CumAIP Q1 group, the HR and 95

Evidence is limited on the incidence of depression and anxiety in relation to active commuting. Our study aimed to explore their association and examine the mediating role of inflammatory. This study included 240,547 workers in the UK Biobank. The exposure variable was the mode of transport used to get to and from work including active (walking, cycling, mixed mode) and non-active commuting (car or public transport). The incidence of depression and anxiety was defined using ICD-10 codes. Cox proportional hazard regression models were used to explore the hazard ratios (HRs) of active commuting with depression and anxiety, and mediation analyses were used to test the mediating role of inflammatory in this association. There were 10,862 depression and 9407 anxiety events. Active commuting was associated with lower risk of depression [cycling: HR 0.775, 95% confidence interval (0.674-0.890); mixed mode walking: 0.858 (0.800-0.919); mixed mode cycling: 0.821 (0.744-0.907)] and anxiety [cycling: 0.781 (0.675-0.904); mixed mode walking: 0.867 (0.805-0.934); mixed mode cycling 0.810 (0.728-0.902)], and there were distinct dose-response trends between commuting distance and incidence of depression or anxiety. Inflammatory explained 19.75% of the association between cycling with depression, and 18.05% with anxiety. There were interactions between commuting and occupation type. Cycle and mix mode commuting were associated with lower risk of depression and anxiety, and inflammation partially mediated these association. Implementing initiatives that facilitate active commuting may help alleviate the poor mental health.

The dynamic and heterogeneous process of obesity measurement can be better assessed by change trajectories. Utilizing multiple metrics to assess obesity could provide more comprehensive insights. Currently, the associations of adiposity measures trajectories with metabolic diseases and plant-based dietary patterns remain unclear. Using latent class mixed modeling approach, we identified body mass index (BMI), waist-to-hip ratio (WHR) and fat mass index (FMI) trajectory groups based on measures acquired at four time points. We examined associations between adiposity measures trajectories and plant-based dietary patterns, using logistic regression. Cox proportional hazards regression models were applied to investigate the association between adiposity measures trajectories and metabolic diseases. We identified two latent classes of BMI trajectories: low-smooth and high-growth-decline, two WHR trajectories: low-growth and high-growth, and two FMI trajectories: low-smooth and high-growth-decline. Participants who had a high healthful plant-based diet index had lower odds of being in the high-growth-decline BMI trajectory (OR = 0.491, 95% CI: 0.402, 0.600), the high-growth WHR trajectory (OR = 0.526, 95% CI: 0.438, 0.632) or the high-growth-decline FMI trajectory (OR = 0.533, 95% CI: 0.446, 0.638). We found that participants in the high-growth-decline BMI trajectory (HR = 1.925, 95% CI: 1.542, 2.404), the high-growth WHR trajectory (HR = 1.314, 95% CI: 1.003, 1.722) or the high-growth-decline FMI trajectory (HR = 1.562, 95% CI: 1.236, 1.975) had higher risks. A healthy plant-based dietary pattern assists in maintaining normal body size over time. Concurrently, long-term stabilization of a normal body size may be linked to a reduced risk of metabolic diseases.

BACKGROUND:Cardio-renal-metabolic multimorbidity is defined as the coexistence of two or three cardio-renal-metabolic diseases, namely cardiovascular disease, type 2 diabetes mellitus, and chronic kidney disease. The association between sleep traits and cardio-renal-metabolic disease progression is often overlooked. Anxiety and depression may affect both sleep and cardio-renal-metabolic diseases, while their mediating role is unclear. METHODS:We conducted a multistate analysis using data from 375,837 UK Biobank participants (42.16% men, mean age 55.77 years, 95.37% White) to investigate the associations between sleep traits and the longitudinal progression from healthy to first cardio-renal-metabolic disease, cardio-renal-metabolic multimorbidity, and death. Sleep traits, including sleep duration, ease of getting up in the morning, chronotype, napping during day, insomnia, and snoring, were self-reported at baseline, and an integrated sleep score was calculated, with higher scores indicating healthier sleep. Counterfactual mediation analysis assessed the role of anxiety and depression. RESULTS:During a median follow-up of 13.68 years, 110,287 participants developed first cardio-renal-metabolic disease, 14,562 experienced cardio-renal-metabolic multimorbidity, and 2709 died. Healthy sleep traits were associated with a decreased risk of progressing from healthy to first cardio-renal-metabolic disease (HR=0.70, 95% CI: 0.67-0.72), healthy to death (HR=0.79, 95% CI: 0.70-0.88), and first cardio-renal-metabolic disease to cardio-renal-metabolic multimorbidity (HR=0.70, 95% CI: 0.64-0.76). Anxiety or depression mediated 16.48% of the first cardio-renal-metabolic disease risk, 14.48% of cardio-renal-metabolic multimorbidity risk, and 25.17% of mortality risk. CONCLUSIONS:Healthy sleep traits were associated with a protective effect in early- to mid-stage cardio-renal-metabolic disease development, with anxiety and depression acting as mediators. Adhering to healthy sleep traits and addressing anxiety and depression may help prevent cardio-renal-metabolic diseases and their progression.

The present study attempted to investigate the associations of PM2.5 and its components with the acute upper respiratory infections (AURI) and the modification effects of temperature and relative humidity (RH). Daily AURI visits data were obtained from Zhengzhou university hospital from 2014 to 2019. Distributed lag nonlinear modelling (DLNM) was used to assess the associations between PM2.5 and its components and AURI morbidity. The modifying effects of temperature and RH on the associations of PM2.5 and its components with AURI were explored by DLNM with cross-base interaction terms of PM2.5 and its components with temperature or RH. During the study period, 87,186 university students visited AURI. The relative risk (RR) per interquartile range (IQR) increase for PM2.5 and its components NO3-, SO42-, NH4+, BC and OM were 1.03 (0.99, 1.09) and 1.05 (0.99, 1.11), 0.98 (0.93, 1.04), 1.02 (0.97, 1.08), 1.07 (1.02, 1.12), 1.08 (1.03, 1.15), respectively. Low temperature increased the adverse effects of PM2.5 and its components NO3-, BC, OM. High relative humidity enhanced the adverse effects of PM2.5 and its components NO3-, NH4+, BC, OM. The adverse effects of NO3-, BC, and OM were only evident in the female university students and during the cold season. PM2.5 components may adversely affect AURI morbidity in university students. Low temperatures and high relative humidity may exacerbate the deleterious effects of PM2.5 components. This reminds us to enhance the prevention of AURI caused by PM2.5 components, especially in cold and humid meteorological conditions.

Aims The association between female reproductive factors and migraine risk remains inconclusive. This study aimed to investigate the association between reproductive factors and migraine. Methods This study included 268,440 female participants enrolled in the UK Biobank from 2006 to 2010. Cox proportional hazard models and restricted cubic spline were used for association analyses. Results With a median of 13.67 years follow-up, a total of 4,394 cases of migraine were documented. The adjusted HR (95 % CI) for menarche > 14 years was 1.16(1.04,1.28) compared with 12 to 14 years; 1.48(1.32,1.66) for menopause < 45 years compared with 45 to 55 years; 1.32 (1.18,1.48) for reproductive life expectancy < 33 years compared with 33 to 40 years; 1.60(1.43,1.79) for hysterectomy; 1.52(1.37,1.69) for oophorectomy; 1.31(1.19,1.45) for pregnant; 1.66(1.47,1.86) for first live birth < 22 years compared with > 27 years; 1.31(1.17,1.47) for last live birth < 27 years compared with > 33 years; 1.16(1.03,1.30), 1.16(1.06,1.27), and 1.17(1.05,1.29) for 1, 2, and 3 or more children compared with no children; 1.18(1.10,1.28) for miscarriages; 1.13(1.04,1.24) for abortions; 1.62(1.51,1.74) for using HRT. Age at menarche, age at first or last live birth, age started oral contraceptive pills, age started HRT, and HRT duration were nonlinearly associated with migraine risk (P < 0.001). Discussion Female reproductive factors, including gynecologic surgery, early first birth, and using HRT, were associated with incident migraine. The findings emphasize the need to incorporate reproductive history into clinical profiles and provide an evidence base for personalized prevention strategies in women.

AIMS:This study aimed to assess the educational inequalities in cardiovascular disease (CVD), coronary heart disease (CHD), and stroke among four generations, and to analyse the mediating role of healthy lifestyles and metabolic factors. METHODS AND RESULTS:This prospective cohort study included 447 227 participants from UK Biobank, with a mean age of 56.10 (8.08) years, divided into four generations born in 1930s, 1940s, 1950s, and 1960s. Cox regression models and the relative index of inequality (RII) were employed to estimate educational inequality on CVD, CHD, and stroke. Counterfactual mediation analysis was utilized to estimate the mediating effects of healthy lifestyles and metabolic factors. After a median of 13.39 years follow-up, 81 470 cases of CVD were documented. In the fully adjusted model, compared to participants with college education, participants with primary school or below had hazard ratios [95% confidence interval (CI)] for CVD of 1.03 (0.96, 1.11), 1.05 (1.03, 1.08), 1.15 (1.10, 1.20), and 1.37 (1.25, 1.51) in 1930s, 1940s, 1950s, and 1960s, respectively. RII (95% Cl) in CVD increased from 1.04 (0.94,1.14) in the 1930s to 1.35(1.22,1.49) in the 1960s. Across all generations, the proportion mediated by healthy lifestyles and metabolic factors on CVD was 13.36-21.72% and 30.65-40.70%, respectively. Similar results were observed for CHD and stroke. CONCLUSION:Educational inequalities in CVD incidence persisted across generations, with potentially greater disparities in 1960s. Implementing effective interventions for healthy lifestyle and metabolic factors that target the less educated population may help reduce these health disparities.

Emerging evidence suggested a potential link between lipid-lowering therapies and neurocognitive effects, raising concerns regarding the possible adverse impact of PCSK9 inhibitors on memory loss. We extracted adverse events associated with memory loss for PCSK9 inhibitors from the Food and Drug Administration Adverse Event Reporting System (FAERS), covering the period from the first quarter (Q1) of 2022 to Q1 of 2025. Reporting odds ratio (ROR), Medicines and Healthcare Products Regulatory Agency (MHRA), empirical Bayesian geometric mean (EBGM), and information component (IC) were used for pharmacovigilance analysis. Drug target Mendelian randomization (MR) was utilized to assess the causal association between PCSK9 inhibitors and memory loss. A total of 389 occurrences of memory loss associated with PCSK9 inhibitors were recorded among 388 patients. In the pharmacovigilance analysis, memory loss did not show a significant signal for PCSK9 inhibitors in both the full dataset [ROR (95% CI): 0.79 (0.72, 0.88); PRR = 0.79, χ2 = 20.64; EBGM05 = 0.73; IC025 = −2.00] and the lipid-lowering targets dataset [ROR (95%CI): 0.59 (0.53, 0.66); PRR = 0.59, χ2 = 95.33; EBGM05 = 0.59; IC025 = −2.30]. The drug target MR revealed no causal association between PCSK9 inhibitors and memory loss (p < 0.05). The present study failed to establish a causal relationship between PCSK9 inhibitors and memory loss. By providing both real-world and genetic evidence, our findings might help alleviate concerns and support the notion that PCSK9 inhibitors were relatively safe regarding memory function.

BACKGROUND AND AIM:Atrial fibrillation (AF) frequently coexists with other complications, including myocardial infarction (MI), heart failure (HF), stroke, and dementia. The contribution of metabolic dysfunction-associated steatotic liver disease (MASLD) to the development and mortality of AF was under-recognized. This study aims to investigate the impact of MASLD on the progression of AF and the mediating effect of carotid intima-media thickness (cIMT). METHODS AND RESULTS:Multistate analysis was conducted to investigate the associations of MASLD with the progression from health to AF, further AF-related complications, and ultimately death. Counterfactual mediation analysis was employed to quantify the extent to which cIMT explained the associations of MASLD with AF, AF-related complications, and death. As many as 350,745 participants were followed for a median of 13.67 (IQR = 12.94 to 14.38) years. Among them, 21,240 (6.06 %) participants experienced AF, 5,808 (27.34 %) developed AF-related complications, afterwards, 1,854 (31.92 %) were died. Compared with non-MASLD, MASLD patients exhibited a higher risk of transitions from health to AF, then to AF-related complications, particularly transition from health to AF, with HR was 1.52 (95 % CI: 1.48-1.57). The proportion mediated by cIMT for AF, AF-related complications, and mortality were 16.51 %, 18.06 %, and 15.14 %, respectively. CONCLUSIONS:Our study revealed that MASLD heightened the risk of the longitudinal advancement of AF, with cIMT recognized as a crucial mediator. This highlights the significance of managing MASLD patients and monitoring atherosclerosis for the subclinical prevention of AF progression.

BACKGROUND:Educational attainment (EA) was associated with lifestyle behaviors and underlying mental disorders. However, the causality remained poorly understood. This study aimed to elucidate the causal association between EA and mental disorders while exploring the mediation role of lifestyle factors. METHODS:A two-step Mendelian randomization (MR) analysis was performed to evaluate the mediation role of lifestyle factors in the relationship between EA and mental disorders. The total effects of years of education (EduYears) and college completion (College) on 31 lifestyle factors and 7 mental disorders were estimated using univariable MR. Multivariable MR was utilized to assess the independent effects of lifestyle factors on mental disorders. Mediation effects were calculated for factors significantly associated with both EA and mental disorders. RESULTS:EduYears was significantly associated with anorexia nervosa (AN), major depression disorder (MDD), post-traumatic stress disorder (PTSD), and attention deficit hyperactivity disorder (ADHD), with OR (95% CIs) of 0.96 (0.92, 0.99), 0.97 (0.94, 1.00), 0.94 (0.91, 0.97), and 0.84 (0.82, 0.87), respectively. Similarly, genetically determined College was inversely associated with AN, MDD, PTSD, and ADHD. Smoking initiation, processed meat intake, beef intake, and cereal intake mediated the effect of EA on mental disorders from 9% to 31%. CONCLUSION:This study indicated the causal effect of EA on AN, MDD, PTSD, and ADHD. The mediation analysis indicated that smoking and diet partially explained the effect. The results underscored the significance of EA and lifestyle factors in mental health policies.

OBJECTIVE:The long-term effects of PM2.5 components and green space on cardiometabolic multimorbidity (CMM) remain unclear. This study aims to investigate the associations between PM2.5 components, green space, and their interaction with CMM. METHODS:A total of 10,300 participants were included from the China Health and Retirement Longitudinal Study (CHARLS). The associations between PM2.5 components, green space, and their interaction with CMM were examined using logistic regression models. RESULTS:Each interquartile range (IQR) increase in PM2.5 and its components was positively associated with CMM. The odds ratios (ORs) for CMM associated with exposure to PM2.5, organic matter, and nitrate (NO3-) were 1.326 (95% CI: 1.158-1.518), 1.232 (95% CI: 1.081-1.298), and 1.119 (95% CI: 1.041-1.382), respectively. The OR for CMM with each IQR increase in the Normalized Difference Vegetation Index was 0.776 (95% CI: 0.695-0.866). Green space was found to mitigate the adverse impacts of PM2.5 and its components on CMM. CONCLUSION:Long-term exposure to PM2.5 and its components have been positively associated with CMM. Green space may help mitigate the positive association between air pollutants and CMM.

BACKGROUND:The impact of dynapenic obesity on the progression of cardiometabolic multimorbidity (CMM) remains poorly understood. This study aimed to explore the association between dynapenic obesity and cardiometabolic diseases (CMD) progression, as well as the mediating roles of C-reactive protein (CRP) and the atherogenic index of plasma (AIP). METHODS:The study included 446,862 UK Biobank participants. CMM was defined as the coexistence of two or three CMDs, including type 2 diabetes (T2DM), coronary heart disease (CHD) and stroke. Dynapenic obesity was classified into dynapenic general obesity and dynapenic abdominal obesity, assessed by handgrip strength (HGS), body mass index (BMI), and waist circumference (WC). A multi-state model was employed to evaluate the influence of dynapenic obesity on CMD progression. Counterfactual mediation analyses were conducted to investigate the mediating role of CRP and AIP. RESULTS:Over a median 13.67-years follow-up, 54,555 participants developed CMD, 5842 developed CMM, and 32,930 died. Compared with non-dynapenia and non-general obesity (ND/NGO), the HRs (95% CI) of first CMD (FCMD), CMM, and death for dynapenia and general obesity (D/GO) were 2.75 (2.61,2.90), 4.61 (4.05,5.24), and 1.68 (1.56,1.80), respectively. Similar results were observed for dynapenic abdominal obesity. Compared with ND/NGO, the proportions of CRP and AIP mediated associations of D/GO with FCMD risk were 19.58% (95% CI: 18.66%, 20.18%) and 18.99% (95% CI: 18.12%, 19.62%), respectively, which were lower than the proportions mediated in the associations of dynapenia and abdominal obesity (D/AO) with FCMD (CRP: 30.38% vs. 19.58%; AIP: 31.40% vs. 18.99%). Furthermore, CRP and AIP accounted for a greater proportion of the association between dynapenic obesity and CMM than FCMD. CONCLUSION:This study indicated that there are differential effects associated with dynapenic obesity during the longitudinal progression of CMD. CRP and AIP may play a partial role in mediating this association.