Accumulating animal studies have demonstrated associations between ambient air pollution (AP) and metabolic dysfunction-associated fatty liver disease (MAFLD), but relevant epidemiological evidence is limited. We evaluated the association of long-term exposure to AP with the risk of incident MAFLD in Northwest China. The average AP concentration between baseline and follow-up was used to assess individual exposure levels. Cox proportional hazard models and restricted cubic spline functions (RCS) were used to estimate the association of PM2.5 and its constituents with the risk of MAFLD and the dose-response relationship. Quantile g-computation was used to assess the joint effects of mixed exposure to air pollutants on MAFLD and the weights of the various pollutants. We observed 1516 cases of new-onset MAFLD, with an incidence of 10.89%. Increased exposure to pollutants was significantly associated with increased odds of MAFLD, with hazard ratios (HRs) of 2.93 (95% CI: 1.22, 7.00), 2.86 (1.44, 5.66), 7.55 (3.39, 16.84), 4.83 (1.89, 12.38), 3.35 (1.35, 8.34), 1.89 (1.02, 1.62) for each interquartile range increase in PM2.5, SO42-, NO3-, NH4+, OM, and BC, respectively. Stratified analyses suggested that females, frequent exercisers and never-drinkers were more susceptible to MAFLD associated with ambient PM2.5 and its constituents. Mixed exposure to SO42-, NO3-, NH4+, OM and BC was associated with an increased risk of MAFLD, and the weight of BC had the strongest effect on MAFLD. Exposure to ambient PM2.5 and its constituents increased the risk of MAFLD.

OBJECTIVE: To compare antibody responses after vaccinations between patients with rheumatoid arthritis (RA) and patients with metabolic disorders (MD). The study places special emphasis on understanding how common diseases affect antibody responses in individuals with RA within real-world settings.
METHODS: The participants were 117 patients with RA (66 with RA only and 51 with RA and MD) and 37 patients with MD who received both the primary series of vaccinations and a booster. Antibody titers were compared after the primary series of vaccinations and a booster, and factors influencing the antibody response were assessed.
RESULTS: Following the primary series of vaccinations, a significant reduction in antibody titers was observed in patients with longer days between vaccination and antibody measurement, the use of IL-6 inhibitors, selective T cell co-stimulation modulators, and methotrexate. Comorbid MD did not exhibit significant influences on antibody response in RA. Notably, the presence of RA itself was not significant in multivariate linear regression analysis. After the administration of the booster, however, day between vaccination and antibody measurement, the use of IL-6 inhibitor, and methotrexate no longer remained significant. Only the use of selective T cell co-stimulation modulators retained its significance.
CONCLUSIONS: MD did not exhibit a significant impact on antibody responses in RA patients. The reduced antibody response following the primary series in RA patients appeared to be attributed more to specific RA medications rather than to the disease itself. Booster vaccines are vital in restoring the antibody response in RA.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is emerging globally as a significant problem. The mainstay of treatment is lifestyle intervention (LSI). We hypothesized that providing information regarding LSI and MASLD through a social media application generally used in the respective society would improve clinical outcomes in MASLD more than standard of care (SOC). This is a randomized controlled study in noncirrhotic MASLD patients aged 18-65 years in Thailand. Eligible patients were randomly assigned to either the control (SOC) or intervention arm. Patients in both groups received standard LSI advice. Infographics about MASLD and LSI information were sent to the intervention group every 3-7 days via the LINE official account. The outcomes are changes in liver steatosis and liver stiffness by FIBROSCAN at 24 weeks, as well as weight loss, body composition, and serum alanine aminotransferase (ALT) level between the two groups. A total of 122 patients were enrolled. The median age of eligible participants was 53 years, 64.7% were female, and median body mass index was 27.3 kg/m2. After a complete 24-week study period, both groups had an improvement in weight, ALT level, liver steatosis, and fat mass, but the differences in those changes between groups were not statistically significant. Interestingly, a significant improvement in liver stiffness was observed in the intervention group than in the control group (- 0.7 ± 1.8 kPa vs. 0.1 ± 2.4 kPa, P = 0.035). Encouraging LSI and delivering MASLD information via a social media application (LINE official account) to patients with MASLD demonstrated a better outcome of liver stiffness measurement than SOC.Clinical trial number: TCTR20210304002 (04/03/2021) ( http://www.thaiclinicaltrials.org/show/TCTR20210304002 ).

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP.
METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality.
RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries.
CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

Patients with metabolic dysfunction-associated fatty liver disease (MAFLD) often present with concomitant metabolic dysregulation and alcohol consumption, potentially leading to distinct clinical outcomes. We analyzed data from 8043 participants with MAFLD in the Thai National Health Examination Survey with linked mortality records. According to the MAFLD criteria, 1432 individuals (17.2%) were categorized as having the diabetes phenotype, 5894 (71.0%) as the overweight/obesity phenotype, and 978 (11.8%) as the lean metabolic phenotype. Over 71,145 person-years, 916 participants died. Using Cox proportional hazard models adjusting for physiological, lifestyle, and comorbid factors, both diabetes (adjusted hazards ratio [aHR] 1.59, 95% CI 1.18-2.13) and lean metabolic phenotypes (aHR 1.28, 95% CI 1.01-1.64) exhibited significantly higher mortality risk compared to the overweight/obesity phenotype. A J-shaped relationship was observed between daily alcohol consumption and the risk of all-cause mortality. Daily alcohol intake exceeding 50 g for women and 60 g for men increased the all-cause mortality risk among MAFLD individuals with the lean metabolic phenotype (aHR 3.39, 95% CI 1.02-11.29). Our study found that metabolic phenotype and alcohol consumption have interactive effects on the risk of all-cause mortality in patients with MAFLD, indicating that evaluating both factors is crucial for determining prognostic outcomes and management strategies.

BACKGROUND: Compound Zaoren Granules (CZG), an optimized herbal formulation based on the traditional Chinese medicine prescription Suanzaoren decoction, are designed specifically for insomnia treatment. However, the mechanisms underlying its efficacy in treating insomnia are not yet fully understood.
OBJECTIVE: The research investigated the mechanisms of CZG\'s improvement in insomnia by regulating cAMP/CREB signaling pathway and metabolic profiles.
METHODS: The main components of CZG were characterized by liquid chromatography-mass spectrometry (LC-MS). Subsequently, these validated components were applied to network pharmacological analysis to predict signaling pathways associated with insomnia. We evaluated the effect of CZG on BV-2 cells in vitro. We also evaluated the behavioral indexes of CUMS combined with PCPA induced insomnia in rats. HE staining and Nissl staining were used to observe the pathological damage of hippocampus. ELISA was used to detect the levels of various neurotransmitters, orexins, HPA axis, and inflammatory factors in insomnia rats. Then we detected the expression of cAMP/CREB signaling pathway through ELISA, WB, and IHC. Finally, the metabolomics was further analyzed by using UHPLC-QTOF-MS/MS to investigate the changes in the hippocampus of insomnia rats and the possible metabolic pathways were also speculated.
RESULTS: The results of CZG in vitro experiments showed that CZG has protective and anti-inflammatory effects on LPS induced BV-2 cells. A total of 161 chemical components were identified in CZG. After conducting network pharmacology analysis through these confirmed components, we select the cAMP/CREB signaling pathway for further investigate. The behavioral research results on insomnia rats showed that CZG significantly prolonged sleep time, mitigated brain tissue pathological damage, and exhibited liver protective properties. CZG treats insomnia by regulating the content of various neurotransmitters, reducing levels of orexin, HPA axis, and inflammatory factors. It can also treat insomnia by upregulating the expression of the cAMP/CREB signaling pathway. Hippocampus metabolomics analysis identified 69 differential metabolites associated with insomnia. The metabolic pathways related to these differential metabolites have also been predicted.
CONCLUSIONS: These results indicate that CZG can significantly prolong sleep time. CZG is used to treat insomnia by regulating various neurotransmitters, HPA axis, inflammatory factors, cAMP/CREB signaling pathways, and metabolic disorders.

OBJECTIVE: Long working hour is a known risk factor for metabolic diseases. We explored the association between working hours and metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS: Data on working hours among 22,818 workers (11,999 females) from the Korea National Health and Nutrition Examination Survey (2013-2021) were used for this study.
METHODS: MASLD was defined as a combination of hepatic steatosis combined with one or more of cardiometabolic risk factors (overweight/obesity, prediabetes/diabetes, raised blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol). Hepatic steatosis was assessed using the hepatic steatosis index. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: The overall prevalence of MASLD was 30.4% in men and 18.1% in women. Among male workers, 20.2% worked ≥55 h/week, whereas among female workers, 10.1% worked ≥55 h/week. Compared with working 35-40 h/week, working ≥55 h/week was positively associated with overweight/obesity (OR: 1.21; 95% CI: 1.05-1.40), pre-diabetes mellitus (pre-DM)/DM (OR: 1.20; 95% CI: 1.04-1.38), raised blood pressure (OR: 1.17; 95% CI: 1.02-1.35), and presence of any cardiometabolic risk factors (OR: 1.56; 95% CI: 1.21-2.02). The adjusted OR (95% CI) of the association between working hours and MASLD was 1.27 (1.09-1.47) for ≥55 h/week compared with working 35-40 h/week in male workers. In female workers, long working hours were not clearly associated with cardiometabolic risk factors and MASLD.
CONCLUSIONS: Long working hours are positively associated with MASLD among Korean male workers. Policy interventions are needed to mitigate the adverse metabolic effects of prolonged working hours.

UNASSIGNED: The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups.
UNASSIGNED: This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves.
UNASSIGNED: Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m2 and 4.0% decrease in the overall cohort, 0.85 kg/m2 and 3.9% decrease in males, and 1.2 kg/m2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m2, the cutoff values were 0.75 kg/m2 and 2.7% BMI reduction.
UNASSIGNED: Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population.

UNASSIGNED: Several observational studies have documented a potential link between obesity and peripheral artery disease (PAD), although conflicting findings exist. The causal relationship between obesity and PAD continues to be a subject of ongoing debate in the medical community.
UNASSIGNED: In this study, we employed a bidirectional Mendelian randomization (MR) analysis to explore the potential causal relationship between obesity and the risk of PAD.
UNASSIGNED: To investigate these causal relationships, we conducted bidirectional MR analysis using publicly available genome-wide association study (GWAS) data. Effect estimates were calculated using the random-effects inverse variance-weighted (IVW) method.
UNASSIGNED: We identified eight independent single nucleotide polymorphisms (SNPs) associated with obesity in 218,735 samples involving 16,380,465 SNPs, all of which met the genome-wide significance threshold (p < 5 × 10-⁸). The IVW analysis indicates a significant positive association between genetic obesity and multiple datasets with PAD as the outcome: Queue-1 (GWAS ID: finn-b-I9_PAD) (OR = 1.138, 95% CI: 1.027-1.261, p = 0.013), Queue-2 (GWAS ID: bbj-a-144) (OR = 1.190, 95% CI: 1.019-1.390, p = 0.028), Queue-3 (GWAS ID: ebi-a-GCST90018670) (OR = 1.174, 95% CI: 1.014-1.360, p = 0.032), and Queue-4 (GWAS ID: ebi-a-GCST90018890) (OR = 1.194, 95% CI: 1.099-1.296, p < 0.001). However, we did not observe a significant genetic-level association between obesity and PAD for Queue-5 (GWAS ID: ukb-d-I9_PAD) (OR = 1.001, 95% CI: 1.000-1.002, p = 0.071). Furthermore, we conducted a reverse causal MR analysis to explore the potential reverse causal relationship between obesity and PAD. This comprehensive analysis did not provide evidence of a reverse causal association between these two factors.
UNASSIGNED: In summary, our study offers genetic evidence suggesting a possible causal link between obesity and PAD. While we did not find evidence supporting the \"obesity paradox\", prudent weight management remains crucial, as lower weight does not necessarily guarantee better outcomes. As with any study, caution is required in interpreting the findings. Further research is essential to assess the clinical relevance of weight in preventing PAD, which could inform the development of more precise intervention strategies.

Compared with full-term infants, preterm infants have fat-free mass deficit in the first months of life, which increases the risk of metabolic diseases in the future. In this cohort of children born under 32-week gestational age or less than 1500 g, we aimed to evaluate the associations of body composition at term equivalent age and in the first 3 months of life with fat-free mass and fat mass percentage at 4 to 7 years of life. Body composition assessments by air displacement plethysmography and anthropometry were performed at term, at 3 months of corrected age, and at 4 to 7 years of age. Multiple linear regression analysis was used to observe the associations between body composition at these ages. At term, fat mass percentage showed a negative association and fat-free mass a positive association with fat-free mass at 4 to 7 years. The fat-free mass at 3 months and the gain in fat-free mass between term and 3 months showed positive associations with fat-free mass at 4 to 7 years.   Conclusion: Body composition at preschool age is associated with fat-free mass in the first 3 months of life, a sensitive period for the risk of metabolic diseases. What is Known: • Preterm infants have a deficit in fat-free mass and high adiposity at term equivalent age compared to full-term infants. • Fat-free mass reflects metabolic capacity throughout life and therefore is considered a protective factor against the risk of metabolic syndrome. What is New: •Fat-free mass gain in the first 3 months of corrected age is associated with fat-free mass at preschool and school ages. •The first 3 months of life is a sensitive period to the risk of metabolic diseases.