Both ambient air pollution exposure and biological aging are associated with incident liver diseases, but previous studies mainly focused on single-factor associations. This study aimed to assess the combined effects of air pollutant exposure and biological aging on liver diseases incidence and investigate the potential mediating role of biological aging. We analyzed 418 576 UK Biobank participants. Annual mean concentrations of PM2.5, PM10, PM2.5-10, NO2, and NO in 2010 were used to generate a weighted air pollution score. Biological ages were assessed using the Klemera-Doubal method biological age (KDM-BA) and phenotypic age (PhenoAge). Cox regression models and quantile g-computation were used to evaluate associations and joint effects. Mediation analyses explored the role of biological aging. Over a median follow-up of 13.57 years, 7991 (1.91%) participants developed liver diseases. Exposure to all pollutants and biological aging were associated with higher liver diseases risk. And NO2 contributed 42.31% to the mixture effect. Participants with higher levels of air pollutant exposure and biologically older status had a higher risk. Furthermore, the mediated proportion of accelerated biological aging was 1.9% to 7.7% for air pollution-associated liver diseases. Ambient air pollution exposure may increase liver diseases risk, with biological aging potentially involved in the mechanisms.

Objective:To investigate the association between thyroid hormone sensitivity indices and metabolic dysfunction-associated fatty liver disease (MAFLD) in euthyroid Chinese adults. Methods:This cohort study included 5,356 euthyroid patients. The peripheral and central thyroid hormone sensitivity indices were calculated. Cox regression models were used to evaluate associations with MAFLD risk, and restricted cubic splines were used to assess potential nonlinearity. Mediation analyses based on an accelerated failure-time model were used to examine the role of the triglyceride-glucose (TyG) index. Results:MAFLD incidence in euthyroid participants was 18.26%. After adjustment, higher free thyroxine (FT4) levels were inversely associated with MAFLD ( HR = 0.973, 95% CI: 0.948 to 0.999, P = 0.043), whereas higher free triiodothyronine (FT3) levels increased MAFLD risk ( HR = 1.118, 95% CI: 1.000 to 1.250, P = 0.050). Enhanced thyroid hormone sensitivity, as reflected by elevated FT3/FT4 levels and lower total thyroxine resistance index (TT4RI), thyroid stimulating hormone index (TSHI), and thyroid feedback quantile-based index (TFQI FT4), was also associated with a higher incidence (all P < 0.05). Mediation analyses indicated that TyG partially mediated the FT3/FT4-MAFLD and TFQI FT4-MAFLD associations, with indirect effects of -96.27 (95% CI: -124.67 to -70.42) and -4.95 (95% CI: -8.29 to -2.10), respectively. Conclusion:Increased FT3/FT4 and decreased TFQI FT4 levels were significantly associated with a higher MAFLD risk in euthyroid adults, with TyG acting as a partial mediator.

Objectives: Individuals with type 2 diabetes (T2D) remain at high cardiovascular disease (CVD) risk. The pan-immune-inflammation value (PIV) integrates circulating neutrophils, monocytes, platelets, and lymphocytes but does not capture albumin-related nutritional and inflammatory reserve. We investigated associations between the PIV-to-albumin ratio (PIVA) and incident CVD, cardiovascular mortality, and disease progression in individuals with T2D. Methods: This prospective study included 15,355 UK Biobank participants with T2D and no baseline CVD. PIVA was calculated from peripheral blood cell counts and serum albumin and was natural log-transformed. Fine–Gray competing-risk and cause-specific Cox models were used to evaluate incident CVD and cardiovascular mortality. Multi-state models characterized transitions from T2D to CVD and death. We also examined nonlinear associations, renal biomarker mediation, joint associations with the CVD polygenic risk score and triglyceride–glucose index, sensitivity analyses, and external validation of cardiovascular mortality in the National Health and Nutrition Examination Survey. Results: During median follow-ups of 12.94 years for incident CVD and 14.49 years for cardiovascular mortality, 4829 incident CVD events and 514 cardiovascular deaths occurred. Each 1-unit increase in lnPIVA was associated with higher risks of incident CVD (subdistribution hazard ratio [sHR], 1.140; 95% confidence interval [CI], 1.088–1.194) and cardiovascular mortality (sHR, 1.449; 95% CI, 1.247–1.684). Associations were nonlinear. Higher lnPIVA was also associated with transitions from T2D to CVD, from T2D directly to cardiovascular death, and from incident CVD to cardiovascular death. Cystatin C explained a larger proportion of these associations than creatinine. Elevated lnPIVA identified excess cardiovascular risk across strata of genetic susceptibility and insulin resistance, and the findings were generally supported by sensitivity and external validation analyses. Conclusions: lnPIVA was associated with incident CVD, cardiovascular mortality, and adverse cardiovascular transitions in individuals with T2D. As an immune-inflammatory and albumin-based index, PIVA may help identify high-risk individuals beyond conventional cardiometabolic and genetic risk profiles.

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension (HTN) remains unclear despite their known association. Using data from the Beijing Health Management Cohort (BHMC) with a 5-year follow-up, we investigated these bidirectional links through Cox proportional hazards regression and a cross-lagged panel model (CLPM), adjusting for confounders. Systolic/diastolic blood pressure (SBP/DBP) and hepatic steatosis index (HSI) were treated as continuous variables to enhance biological interpretability. Cox regression revealed that HTN increased the risk of NAFLD (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.30, p < 0.05) among participants without NAFLD at baseline, while NAFLD elevated the risk of HTN (HR: 1.11, 95% CI: 1.02-1.21, p < 0.05) among those without HTN at baseline. However, CLPM involving 7349 participants identified a unidirectional temporal relationship from HTN to NAFLD, regression coefficients βSBP2017→HSI2022: 0.036 (95% CI: 0.012, 0.059), βDBP2017→HSI2022: -0.044 (95% CI: -0.068, -0.020), both p < 0.05; but not from NAFLD to HTN, regression coefficients βHSI2017→SBP2022: 0.017 (95% CI: -0.003,0.037), βHSI2017→DBP2022:0.006 (95% CI: -0.016,0.028), both p > 0.05. Overall, our study demonstrates a unidirectional temporal association from HTN to NAFLD. However, a bidirectional relationship was also observed in individuals under 60 years and in those without central obesity. These findings highlight the importance of considering age and central obesity to manage HTN to reduce the risk of future NAFLD and to manage NAFLD to reduce the risk of future HTN.

BACKGROUND:Although some studies examined the association of individual risk factors for cardiovascular-kidney-metabolic (CKM) syndrome (diabetes, chronic kidney disease, and stroke) with the risk of incident dementia, little is known about the impact of overall CKM health on dementia risk. This study investigated (1) the association between CKM syndrome and risk of incident dementia in 400,740 UK Biobank participants and (2) whether systemic inflammation mediated this association. METHODS:The association between CKM syndrome and the risk of dementia was assessed using Cox proportional hazards models. The mediating role of systemic inflammation markers was evaluated in 389,287 individuals. RESULTS:Compared with stage 0 CKM syndrome, stages 3 and 4 were significantly associated with an increased risk of dementia (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.14-1.59; HR, 1.80; 95% CI 1.57-2.07). A significant linear trend was observed between CKM syndrome stages and dementia risk. Stage 2 CKM syndrome with more than two risk factors for CKM significantly increased dementia risk (HR, 1.25; 95% CI 1.07-1.46). Advanced CKM syndrome was associated with an increased risk of dementia (HR, 1.62; 95% CI 1.53-1.71). Four systemic inflammation markers significantly mediated the association between CKM syndrome and the risk of dementia. CONCLUSIONS:Higher stages of CKM syndrome are associated with an increased risk of dementia, and systemic inflammation mediates this association. These results highlight the importance of early and comprehensive management of poor CKM health to reduce the risk of dementia.

Background: Insulin resistance (IR) is strongly related to non-alcoholic fatty liver disease (NAFLD). Triglycerideglucose (TyG) index serves as a novel substitute indicator for IR. However, research on the effect of TyG index on NAFLD remains sparse. This study aims to investigate the causal association between TyG index and incident NAFLD. Methods: The primary cohort consisted of 27,052 participants from the Beijing Health Management Cohort, while the external validation cohort included 75,023 participants from the Taiwan MJ Cohort. Entropy balancing for continuous treatments (EBCT) combined with logistic regression and targeted maximum likelihood estimation (TMLE) were used to evaluate the causal association between the TyG index and incident NAFLD. Results: During a median follow-up of 2.49 years in the primary cohort, 6,168 participants (median age: 36.0 years) developed incident NAFLD. EBCT combined with logistic regression revealed the odds ratio (95 % CI) of NAFLD risk was 1.742 (1.478-2.054) for each 1-unit increase in the baseline TyG index. In the TMLE model, the risk ratio (95 % CI) for NAFLD was 1.540 (1.406-1.687) in the Q4 (quartile 4) group compared with the Q1 group. These findings were consistent with those from the external validation cohort, reinforcing the robustness of the causal relationship between the TyG index and NAFLD incidence. Conclusions: The advanced double-robust estimation method suggests that a higher baseline TyG index may be causally associated with an increased NAFLD risk, providing more reliable evidence for its role as a simple biomarker and demonstrating the utility of double-robust estimation causal inference models in epidemiology.

BACKGROUND:Studies investigating lipid-depression associations have reported inconsistent findings, and few have considered the interrelationships among lipid parameters. Additionally, the moderating role of inflammation in these associations remains unclear. This study aims to (1) assess lipid-depression associations after controlling for other lipid parameters, and (2) explore the moderating effect of inflammation. METHODS:The study included 87,636 participants from the UK Biobank. A pairwise mixed graphical model (MGM) network was constructed in the entire sample to examine the prospective associations between seven lipid parameters and depression. The moderating role of inflammation was explored by: (1) estimating pairwise MGM networks for groups stratified by high-sensitivity C-reactive protein (hs-CRP) levels, (2) conducting network comparison tests (NCTs), and (3) constructing moderated network models (MNMs). RESULTS:In the full-sample network, edges connecting triglycerides (TG, edge weight = 0.034), high-density lipoprotein cholesterol (HDL-C, edge weight = -0.011), low-density lipoprotein cholesterol (LDL-C, edge weight = -0.009), and lipoprotein(a) (Lp(a), edge weight = 0.012) with depression were identified. The non-elevated and elevated hs-CRP networks exhibited opposite signs for the Lp(a)-depression edge. In NCTs, HDL-C-depression and apolipoprotein A1 (Apo A1)-depression showed significant differences in edge weights. hs-CRP moderates the associations of HDL-C, Apo A1, and Lp(a) with depression in MNMs. CONCLUSIONS:After controlling for other lipid parameters, TG and Lp(a) are positively, while HDL-C and LDL-C are negatively associated with depression in the overall study population. Inflammation moderates the associations of HDL-C, Apo A1, and Lp(a) with depression. Our study provides further evidence for the lipid-depression associations.

Background Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world,and the prevalence of NAFLD in China has continued to increase over the past 20 years.Some cohort studies have confirmed the causal relationship between NAFLD and dysglycaemia,but the temporal relationship between the two remains unclear.Objective To analyse the bidirectional time-series association between NAFLD and dysglycemia using cross-lagged panel models with the Beijing Health Management Cohort as the study population.Methods Based on the Beijing Health Management Cohort Study,follow-up data were collected from 2016 to 2021,with one follow-up visit per year,including questionnaire and physical examination information.According to the pre-established inclusion and exclusion criteria,44 838 study subjects were finally included.A cross-lagged panel model was constructed using hepatic steatosis(HS)and fasting plasma glucose(FPG)as surrogate indicators of NAFLD and dysglycaemia,and stratified by gender and BMI to explore the temporal relationship between NAFLD and dysglycaemia in different populations.Results(1)In the total population,the cross-lagged path coefficient βbaseline HS → follow-up FPG was statistically significant(P＜0.05)at 0.009(95%CI=0.002-0.016);however,the cross-lagged path coefficient in the opposite direction was not statistically significant(P＞0.05).(2)In women,the cross-lagged path coefficients in both directions were statistically significant(P＜0.05)with βbaseline HS → follow-up FPG of 0.025(95%CI=0.015-0.035),and βbaseline FPG → follow-up HS of 0.026(95%CI=0.014-0.038);in men,the cross-lagged path coefficients in both directions were not statistically significant(P＞0.05).(3)Among those with BMI≥25.0 kg/m2,the cross-lagged path coefficient βbaseline HS → follow-up FPG was statistically significant(P＜0.05)at 0.114(95%CI=0.103-0.125);however,the cross-lagged path coefficients in the opposite direction were not statistically significant(P＞0.05);and among those with BMI＜25.0 kg/m2,the cross-lagged path coefficients in both directions were statistically significant(P＞0.05).Cross-lagged path coefficients were statistically significant(P＜0.05),with βbaseline HS → follow-up FPG of 0.101(95%CI=0.092-0.111)and βbaseline FPG→follow-up HS of 0.021(95%CI=0.012-0.031).Conclusion There was a unidirectional temporal relationship from NAFLD to dysglycaemia in the total population and in the population with BMI≥25.0 kg/m2;and there was a bidirectional temporal relationship between NAFLD and dysglycaemia in the female population and in the population with BMI＜25.0 kg/m2,which provides clues for adopting the treatment idea of co-prevention of the two disorders,NAFLD and dysglycaemia,in clinical practice.

BACKGROUND:Environmental chemical exposure has emerged as an important risk factor for cardiometabolic and other chronic diseases. Cardiovascular-kidney-metabolic (CKM) syndrome conceptualizes the overlap of cardiovascular, kidney, and metabolic diseases as a systemic condition, providing a comprehensive framework for systematically identifying their risk factors. This study aimed to assess the associations between multiple environmental chemicals and CKM syndrome and to examine the potential mediating role of inflammation. METHODS:The analysis was based on NHANES data from the 2013-2016 period. An exposome-wide approach was applied to identify environmental chemicals associated with CKM syndrome. Restricted cubic splines (RCS) were used to examine potential nonlinear associations. To evaluate the joint associations of multiple exposures, both weighted quantile sum (WQS) regression and quantile-based g-computation (Qgcomp) were employed. Mediation analyses were performed to explore inflammation as a possible pathway. RESULTS:Six environmental chemicals were found to be associated with CKM syndrome, including metals (tin), volatile organic compound metabolites (VOCMs: n-A-S-(3-hydrxprpl-1-metl)-L-cys, n-ace-S-(3,4-dihidxybutl)-L-cys), polycyclic aromatic hydrocarbons (PAHs: 1-hydroxyphenanthrene, 2&3-hydroxyphenanthrene), and iodine. A U-shaped relationship was observed between barium, cobalt, strontium, thallium, nitrate, and 2&3-hydroxyphenanthrene and the risk of advanced CKM syndrome. Mixed exposure analyses suggested that combined exposure to multiple metals was associated with a higher risk of advanced CKM syndrome. Moreover, inflammation may mediate the association between environmental chemicals and CKM syndrome. CONCLUSION:This study underscored the importance of controlling exposure to harmful environmental chemicals in the prevention and control of chronic multisystem diseases, and provided new research perspectives for elucidating the potential biological mechanisms underlying CKM syndrome.

The prevalence of cardiometabolic multimorbidity (CMM) has increased substantially in recent years. Previous studies have established the associations between vitamin D, vitamin D receptor (VDR) polymorphisms, and the risk of individual cardiometabolic disease (CMD). However, the role of these factors in the progression of CMD to CMM or mortality remains unclear. This study aimed to investigate the associations between vitamin D, VDR polymorphisms, and the dynamic progression of CMM, as well as to explore the potential modification effect of VDR polymorphisms. Data for this cohort study were extracted from the UK Biobank. CMM was defined as the coexistence of at least two CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. A multi-state model was used to analyze associations between serum 25(OH)D, VDR polymorphisms and the dynamic progression of CMM. The sample included 396,192 participants. Over a median follow-up of 13.8 years, 55,772 individuals experienced at least one CMD and 28,624 died. Compared to participants with 25(OH)D < 25 nmol/L, those with 25(OH)D ≥ 75 nmol/L had HRs of 0.70 (95

Aim: To investigate the natural history and progression of non-alcoholic fatty liver disease (NAFLD) in Chinese adults using a community-based longitudinal cohort. Methods: We analyzed data from 24,893 adults in the Beijing Health Management Cohort (2016–2021) with annual follow-up, including questionnaires, physical examinations, and laboratory tests. Participants were categorized into three states: healthy (S1, n = 17,906), NAFLD with body mass index (BMI) < 24 kg/m2 (S2, n = 1,139), and NAFLD with BMI ≥ 24 kg/m2 (S3, n = 5,848). Transition probabilities, mean sojourn times, and determinants of progression were estimated using a multi-state Markov model, with analyses stratified by sex. Results: Most individuals remained in their baseline state. Females in S1 were more likely to stay healthy than males (93.76% vs. 83.52%), while males had a higher risk of progression to S3 (12.59% vs. 4.23%). Females in S3 had a greater chance of reverting to S1 (21.33% vs. 18.18%). Mean sojourn time in S1 was longer for females (18.58 vs. 6.97 years), whereas males spent more time in S3 (5.37 vs. 4.18 years). Age, hyperuricemia, abdominal obesity, high triglycerides, and low high-density lipoprotein cholesterol (HDL-C) significantly increased the risk of progression. Conclusions: Sex differences strongly affect NAFLD progression in Chinese adults. Males are more likely to deteriorate, while females show higher recovery. Metabolic factors and obesity are key targets for early prevention and intervention.

Objectives: Previous studies have confirmed that biological age (BA) acceleration is associated with single cardio-renal–metabolic diseases (CRMDs), typically including type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease. However, its association with progression to cardio-renal–metabolic multimorbidity (CRMM, coexistence of ≥2 CRMDs) and subsequent mortality remains unexplored. Methods: Using the multi-state model, we analyzed 278,927 UK Biobank participants free of CRMDs at baseline to investigate the association between BA acceleration—measured by phenotypic age (PhenoAge) and Klemera–Doubal method age (KDMAge)—and CRMM progression trajectory, from health to the first CRMD and then to CRMM and death. BA acceleration was the residual from regressing BA on chronological age; positive values indicated a biologically older individual. Results: PhenoAge acceleration showed stronger associations than KDMAge acceleration. Per the 1-SD increase in PhenoAge acceleration; HRs (95% CIs) were observed at 1.18 (1.17–1.19) for baseline to first CRMD; 1.24 (1.22–1.26) for first CRMD to CRMM; 1.25 (1.22–1.27) for baseline to death; 1.13 (1.11–1.15) for first CRMD to death; and 1.09 (1.06–1.12) for CRMM to death. Biologically older individuals by PhenoAge acceleration showed greater reductions in CRMD-free and total life expectancy than those by KDMAge acceleration. Age, socioeconomic status, education, smoking status, alcohol consumption, physical activity, and diet-modified risks for specific transitions. Conclusions: BA acceleration, particularly PhenoAge acceleration, relates to higher CRMM progression risk and shorter life expectancy. Combining BA acceleration with sociodemographic or lifestyle factors improves risk identification for specific transitions. BA acceleration offers the potential to guide CRMM prevention across its entire progression.

Background and aim: Previous studies have demonstrated an association between SUA and dyslipidemia. This study aims to explore the temporal relationship between SUA and dyslipidemia. Methods and results: Based on the Beijing Health Management Cohort conducted from 2013 to 2018, the data of a physical examination population was collected, including a total of 6630 study subjects. Cross -lagged panel analysis was employed to examine the temporal relationship between elevated SUA levels and dyslipidemia, indicated by either elevated TG or decreased HDL-C. The path coefficient and the 95 % CI from baseline TG to follow-up SUA were as follows: in the general population, men, women, and people with BMI >= 25 kg/m(2)were 0.027 (0.008 -0.045), 0.024 (0.001-0.048), 0.032 (0.001-0.063) and 0.033 (0.006-0.059) (P < 0.05); however, the path coefficient from baseline SUA to follow-up TG and the 95 % CI were not statistically significant. Furthermore, the path coefficients and 95 % CIs between elevated SUA and decreased HDL-C were not statistically significant, both in the general population and in populations stratified by gender and BMI. Conclusions: We found a temporal relationship from elevated TG to elevated SUA in the general population and the populations stratified by gender and BMI (>= 25 kg/m(2)). However, we did not observe a reverse relationship from elevated SUA to elevated TG. Additionally, we did not find a temporal relationship between decreased HDL-C and elevated SUA in both the general population and the stratified populations. (c) 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

BACKGROUND:Sepsis is a life-threatening condition caused by the body's severe response to infection,leading to widespread inflammation and organ failure.Ulinastatin,a glycoprotein hydrolase inhibitor from human urine,has anti-inflammatory properties and has shown potential in improving the outcomes in sepsis patients. OBJECTIVE:To systematically review the efficacy and safety of ulinastatin to clarify its clinical benefits in the treatment of sepsis. METHODS:Through searches of PubMed,Embase,Cochrane Library,and four Chinese databases(SINOMED,CNKI,VIP,and WANFANG data),we searched for published randomized controlled trials from January 1,2004,to November 30,2023.Stata 16.0 software was used to perform the meta-analysis. RESULTS:A total of 39 articles were included(37 in Chinese and 2 in English),involving a total of 2,911 patients.The results of meta-analysis show that the treatment of ulinastatin could reduce mortality(risk ratio[RR]=0.52,95%confidence interval[CI][0.43,0.63],P<0.05),multiple organ dysfunction syndrome(RR=0.30,95%CI[0.18,0.49],P<0.05),length of intensive care unit stay(mean difference[MD]=-5.42,95%CI[-8.13,-2.71],P<0.05),time on mechanical ventilation(MD=-5.84,95%CI[-7.60,-4.07],P<0.05),and length of hospital stay(MD=-12.40,95%CI[-15.03,-9.77],P<0.05).Nine articles reported adverse reactions,of which 1 article reported no obvious adverse reactions. CONCLUSIONS:The results of this meta-analysis show that ulinastatin reduces sepsis case-fatality rate and improves other related outcomes,suggest that ulinastatin is effective in the treatment of sepsis.

Elevated arterial stiffness has been associated with exposure to heavy metals such as lead (Pb) and cadmium (Cd). However, the collective impact of multiple metals and the underlying mechanisms are not fully elucidated. The purpose of this study was to assess the combined effects of exposure to nine heavy metals on arterial stiffness and explore whether serum alkaline phosphatase (ALP) acts as a mediator in this relationship. In the retrospective analysis, data from 8,700 participants were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Arterial stiffness was measured by estimated pulse wave velocity (ePWV). The cumulative impact of exposure to multiple metals was examined using adaptive elastic-net, environmental risk score, weighted quantile sum regression, and quantile g-computation. Additionally, mediation analysis was conducted to explore the potential mediating role of serum ALP. We found that combined exposure to multiple metals was consistently associated with elevated ePWV, with Ba, Pb, and Sb exhibiting the greatest contributions. Notably, serum ALP partially mediated the associations between individual (Pb, Sb) and mixed metal exposure with ePWV, with mediation proportions at 10.76% for Pb, 18.22% for Sb, and 11.07% for mixed metal exposure. In conclusion, this study demonstrates a clear association between exposure to heavy metals, either individually or in combination, and heightened arterial stiffness. Furthermore, the findings suggest that serum ALP activity may act as a mediator in these relationships.

BACKGROUND AND AIMS:Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, which lacks effective drug treatments. This study aimed to construct an eXtreme Gradient Boosting (XGBoost) prediction model to identify or evaluate potential NAFLD patients. METHODS AND RESULTS:We conducted a longitudinal study of 22,140 individuals from the Beijing Health Management Cohort. Variable filtering was performed using the least absolute shrinkage and selection operator. Random Over Sampling Examples was used to address imbalanced data. Next, the XGBoost model and the other three machine learning (ML) models were built using balanced data. Finally, the variable importance of the XGBoost model was ranked. Among four ML algorithms, we got that the XGBoost model outperformed the other models with the following results: accuracy of 0.835, sensitivity of 0.835, specificity of 0.834, Youden index of 0.669, precision of 0.831, recall of 0.835, F-1 score of 0.833, and an area under the curve of 0.914. The top five variables with the greatest impact on the onset of NAFLD were aspartate aminotransferase, cardiometabolic index, body mass index, alanine aminotransferase, and triglyceride-glucose index. CONCLUSION:The predictive model based on the XGBoost algorithm enables early prediction of the onset of NAFLD. Additionally, assessing variable importance provides valuable insights into the prevention and treatment of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide, its close correlation with metabolic disorders has been demonstrated in numerous studies in recent years and an expert panel has proposed renaming it metabolic-associated fatty liver disease (MAFLD). NAFLD/MAFLD may not only increase the incidence and mortality of liver-related diseases but also relate to the incidence and mortality of cardiovascular diseases. This article compares the diagnostic criteria of NAFLD/MAFLD and reviews the research progress in the correlation of non-alcoholic fatty liver disease and metabolic-associated fatty liver disease with cardiovascular diseases. The results show that both NAFLD/MAFLD are significantly associated with the increased incidence of cardiovascular diseases and independent risk factors for cardiovascular diseases. Furthermore, MAFLD patients have a higher risk of developing cardiovascular diseases than NAFLD patients. This article provides clinical physicians with the basis for cardiovascular risk assessment and management in NAFLD/MAFLD patients, emphasizing that in addition to the treatment of liver disease, clinical physicians should also focus on the risk of cardiovascular disease in NAFLD/MAFLD patients.

The acceleration of aging is a risk factor for numerous diseases, and diet has been identified as an especially effective anti-aging method. Currently, research on the relationship between dietary nutrient intake and accelerated aging remains limited, with existing studies focusing on the intake of a small number of individual dietary nutrients. Comprehensive research on the single and mixed anti-aging effects of dietary nutrients has not been conducted. This study aimed to comprehensively explore the effects of numerous dietary nutrient intakes, both singly and in combination, on the acceleration of aging. Data for this study were extracted from the 2015–2018 National Health and Nutrition Examination Surveys (NHANES). The acceleration of aging was measured by phenotypic age acceleration. Linear regression (linear), restricted cubic spline (RCS) (nonlinear), and weighted quantile sum (WQS) (mixed effect) models were used to explore the association between dietary nutrient intake and accelerated aging. A total of 4692 participants aged ≥ 20 were included in this study. In fully adjusted models, intakes of 16 nutrients were negatively associated with accelerated aging (protein, vitamin E, vitamin A, beta-carotene, vitamin B1, vitamin B2, vitamin B6, vitamin K, phosphorus, magnesium, iron, zinc, copper, potassium, dietary fiber, and alcohol). Intakes of total sugars, vitamin C, vitamin K, caffeine, and alcohol showed significant nonlinear associations with accelerated aging. Additionally, mixed dietary nutrient intakes were negatively associated with accelerated aging. Single dietary nutrients as well as mixed nutrient intake may mitigate accelerated aging. Moderately increasing the intake of specific dietary nutrients and maintaining dietary balance may be key strategies to prevent accelerated aging.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The relationship between the trajectories of obesity indicators and incident NAFLD is unknown. Therefore, this study aims to explore the sex-speci fic association between the trajectories of obesity indicators and the incidence of NAFLD. Methods and results: In total, 9067 participants were recruited for this longitudinal study. Obesity indicators use body mass index (BMI) and waist circumference (WC). The trajectory of obesity indicators was analyzed using the growth mixture modeling. The multivariate logistic regression model was used to analyze the association between obesity indicators ' trajectories and incident NAFLD. Over a median follow-up of 1.82 years, 1013 (11.74%) participants developed NAFLD. We identi fied BMI and WC change trajectories as the stable group, increasing group, and decreasing group. After adjusting for baseline level and other confounders, multivariate logistic regression analysis showed that compared with stable group of BMI, the increasing group, and decreasing group odds ratio and 95% con fidence interval of NAFLD were 2.10 (1.06-4.15), and 0.25 (0.09 -0.67) in men, and 1.82 (1.08-3.04) and 0.32 (0.16-0.64) in women. Compared with stable group of WC, the increasing group was 2.57 (1.39-4.74) in men, the increasing group, and decreasing group were 2.29 (1.70-3.10) and 0.28 (0.12-0.64) in women. Sensitivity analysis showed that the results were stable. Conclusion: The BMI and WC changing trajectories are signi ficantly associated with the incidence of NAFLD in men and women. Populations of real-world health examinations can be categorized based on obesity indicator changes to prevent NAFLD.

Introduction Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. Methods In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was composed by a stepwise ordinal logistic model in the discovery population. The receiver operating characteristic (ROC) curve with the bootstrapping procedure was used to assess the performance of the glycan score. Results In the discovery population, the adjusted OR of GP20 (digalactosylated monosialylated biantennary with core and antennary fucose), IGP33 (the ratio of all fucosylated monosyalilated and disialylated structures), IGP44 (the proportion of high mannose glycan structures in total neutral IgG glycans), IGP58 (the percentage of all fucosylated structures in total neutral IgG glycans), IGP75 (the incidence of bisecting GlcNAc in all fucosylated digalactosylated structures in total neutral IgG glycans), and the glycan score are 4.03 (95% CI: 3.03-5.36, P<0.001), 0.69 (95% CI: 0.55-0.87, P<0.001), 0.56 (95% CI: 0.45-0.69, P<0.001), 0.52 (95% CI: 0.41-0.65, P<0.001), 7.17 (95% CI: 4.77-10.79, P<0.001), and 2.86 (95% CI: 2.33-3.53, P<0.001), respectively. Individuals in the highest tertile of the glycan score own an increased risk (OR: 11.41), compared with those in the lowest. The average multi-class AUC are 0.822 (95% CI: 0.786-0.849). Findings are verified in the validation population, with an average AUC of 0.807 (95% CI: 0.758-0.864). Discussion Our study demonstrated that IgG N-glycans and the proposed glycan score appear to be promising predictive markers for ESCC, contributing to the early prevention of esophageal cancer. From the perspective of biological mechanism, IgG fucosylation and mannosylation might involve in the carcinogenesis progression of ESCC, and provide potential therapeutic targets for personalized interventions of cancer progression.