Background Ambient temperature and temperature variability (TV) may influence metabolic dysfunction-associated steatotic liver disease (MASLD), but large-scale evidence is lacking. We aimed to quantify nonlinear associations between long-term temperature/TV exposure and MASLD prevalence in China and evaluate their global relevance. Methods In this cross-sectional study of 33,236 adults from 33 Chinese provinces (2010–2020), MASLD was diagnosed via ultrasonography. Meteorological data were linked to residential addresses to calculate long-term temperature/TV. Generalized additive models were employed to delineate nonlinear exposure–response relationships. Global patterns were assessed using Global Burden of Disease (GBD) data in 2021 from 204 countries or territories. Results A reverse J-shaped relationship emerged between ambient temperature and MASLD prevalence (minimum risk at 21.4 °C), with extreme cold (1st percentile) increasing risk (OR = 1.42, 95% CI: 1.11–1.82). TV exhibited a U-shaped association (threshold: 12.2 °C), where extreme low (1st percentile: OR = 1.38, 1.09–1.73) and high TV (99th percentile: OR = 1.15, 1.02–1.34) elevated MASLD risk. Vulnerable subgroups included males, individuals ≥45 years, smokers, and obese individuals. Globally, non-optimal temperature exposure was strongly correlated with age-standardized MASLD prevalence (R = 0.43, p < 0.001), driven predominantly by high-temperature contributions (R = 0.55 vs. 0.18 for low temperature). Conclusion Chronic cold exposure and extreme temperature variability independently increase MASLD risk, with amplified effects in metabolically vulnerable populations. The global correlation between non-optimal temperature exposure and MASLD burden highlights climate change as a critical modifier of liver health. Integrating temperature mitigation into public health strategies may reduce MASLD incidence amid escalating climate challenges.

Myocardial fibrosis is a major driver of heart failure progression, yet noninvasive tools to track its activity are limited. We evaluated fibroblast activation protein (FAP)-targeted [68Ga]Ga-FAPI-04 (FAPI = FAP inhibitor) positron emission tomography/computed tomography (PET/CT) in C57BL/6J mice subjected to transverse aortic constriction (TAC). PET/CT and echocardiography were performed at 2, 4, and 8 weeks post-surgery. Compared to the sham group, TAC mice exhibited significantly elevated myocardial [68Ga]Ga-FAPI-04 uptake at week 2, with progressive intensification at weeks 4 and 8. Although cardiac function remained preserved at week 2, pronounced systolic and diastolic dysfunction (decreased left ventricular ejection fraction [LVEF] and elevated E/A ratio) developed by week 4, deteriorating further by week 8. Correspondingly, histological (wheat germ agglutinin [WGA], Sirius Red, Masson’s) and autoradiographic analyses revealed progressive cardiomyocyte hypertrophy, accompanied by time-dependent increases in collagen deposition and FAP-specific signals. Importantly, a blocking experiment significantly suppressed myocardial uptake, confirming targeting specificity. [68Ga]Ga-FAPI-04 PET/CT provides a specific, noninvasive method to track the progression of myocardial fibrosis. Crucially, increased FAPI uptake precedes the manifestation of cardiac dysfunction, highlighting its significant potential as a promising imaging tool for the early detection and longitudinal monitoring of heart failure.

Individuals with cardiovascular-kidney-metabolic (CKM) syndrome exhibit a substantially elevated risk of all-cause and cardiovascular-specific mortality. Although estimated glucose disposal rate (eGDR) and a body shape index (ABSI) are commonly used indicators for assessing insulin resistance and atherosclerotic risk, respectively, evidence regarding their combined effect on all-cause and cardiovascular-specific mortality in patients with CKM syndrome remains insufficient. Investigating this combined impact may help improve risk stratification in this population. This study utilized data from the National Health and Nutrition Examination Survey (NHANES, 1999–2018), including 18,186 individuals with stage 0–4 CKM syndrome. Cox proportional hazards models, Kaplan–Meier curves and subgroup analyses were used to evaluate the associations between eGDR and ABSI and mortality risk. The integrated discrimination improvement (IDI) and net reclassification index (NRI) were used to assess the incremental prognostic value of eGDR and ABSI. Finally, six machine learning algorithms were applied to develop predictive models. During the follow-up period, a total of 2536 all-cause mortality and 790 cardiovascular-specific mortality were documented. After multivariable adjustment, both low eGDR and high ABSI independently predicted mortality risk. Combined analysis revealed that individuals with both Low-eGDR and High-ABSI had the highest mortality risk: all-cause mortality hazard ratio (HR) = 2.79 (95

BackgroundAccurately assessing habitual diet is essential for nutritional epidemiology. While food frequency questionnaires (FFQs) are a practical tool for large-scale studies, they require population-specific validation due to regional dietary variations. This study aimed to validate a culturally tailored semi-quantitative FFQ for an understudied population in Northwest China, utilizing a digital Chronic Disease Follow-up Platform (CDFP) to enhance data collection and participant engagement.MethodsA culturally specific 62-item FFQ was developed based on local dietary surveys. The FFQ was administered twice (FFQ1, FFQ2) 3 months apart to assess reproducibility. Relative validity was evaluated against the average of three non-consecutive 24-h food records (3d-FR). The CDFP was employed to manage the entire validation study workflow, including recruiting, sending automated short-message reminders for uploading photographs of food records, and scheduling follow-up telephone calls for the completion of two FFQ administrations (FFQ1, FFQ2). Nutrient intakes were calculated using the China Food Composition Database. Statistical analyses included correlations, intraclass correlation coefficients (ICCs), cross-classification into quartiles, weighted kappa statistics, and Bland-Altman plots.ResultsThe FFQ demonstrated good to excellent reproducibility, with a mean ICC of 0.71 between FFQ1 and FFQ2. Energy-adjusted correlation coefficients between the FFQ1 and FFQ2 ranged from 0.46 to 0.82 (mean: 0.70). For validity, cross-classification showed 77.1% of participants were assigned to the same or adjacent quartile on average, with gross misclassification into opposite quartiles averaging 5.2%. Bland-Altman analysis indicated acceptable agreement, though a systematic overestimation by the FFQ was observed for energy and most nutrients. However, we also observed modest to fair validity correlations (mean crude r = 0.31 and energy-adjusted r = 0.22), with several nutrients showing non-significant associations in crude analyses.ConclusionsThe developed FFQ shows reasonable reproducibility and acceptable relative validity for ranking nutrient intakes rather than for estimating absolute intakes among adults in northwest China. The integration of the CDFP proved to be an effective strategy for avoiding loss to follow-ups and ensuring high-quality dietary data collection. Further validation studies in community-based settings with larger and more balanced samples are required.

Background LncRNAs exhibit diverse biological functions and may be crucial in nonalcoholic fatty liver disease (NAFLD) development. Our focus is on the mechanism of lncRNA U62631.5, regulating GPR41 and Butyricicoccus pullicaecorum (B. pullicaecorum), an intestinal bacterium producing butyric acid. Ensembl analysis suggests an interaction between U62631.5 and GPR41. Methods 1. Male C57BL/6 mice were randomly divided into control group, model group, transplantation control group, transplantation model group by using the fecal microbiota transplantation (FMT) technique in this study. The liver tissue and small intestine tissue in each group were observed by hematoxylin-eosin (HE) staining, and liver histopathology was quantitatively assessed using the NAFLD Activity Score (NAS). The expression of U62631.5 and GPR41 in peripheral blood, liver tissue, and small intestine tissues were detected by PCR. Fecal samples were used by16S rRNA sequencing. The contents of short chain fatty acids in intestinal were detected by gas chromatography, and the expression of B. pullicaecorum was detected by PCR. 2.Hepatic lipid accumulation was observed in HepG2 cells. GPR41 promoter function analysis was detected. After siRNA and overexpression of U62631.5, the U62631.5 and GPR41 were further detected by PCR. Results 1. Animal level: Compared with the model group, hepatic lipid accumulation and the injury of intestinal mucosal were improved, the expression of U62631.5 and GPR41 were increased, the content of butyric acid was increased, and B. pullicaecorum was increased in the transplantation model group. The results were contrary to the above results in the model group compared with the control group, the transplantation control group compared with the control group, and the transplantation model group compared with the transplantation control group. 2.Cell levels: It was found that the promoter activity of GPR41 gene was increased significantly by U62631.5. We interfered with U62631.5 by siRNA and found that GPR41 was almost undetectable by PCR. After overexpression of U62631.5, the expression of GPR41 was increased. Conclusion U62631.5 may play a role by regulating adjacent gene GPR41 related intestinal bacteria in NAFLD, and B.pullicaecorum may be one of the intestinal bacteria in this process.

OBJECTIVES:To assess the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI) by evaluating both the large coronary vessels and coronary microcirculation. METHODS:A total of 507 patients with STEMI undergoing successful percutaneous coronary intervention (PCI) were retrospectively enrolled from two centers. The optimal cut-off value (256.5 mmHg·s·m-1) of angio-based microvascular resistance (AMR) for predicting MACCEs was determined by ROC analysis. Combined with a quantitative flow ratio (QFR) threshold of 0.80, the patients were classified into 4 groups: Group 1 (QFR≥0.8, AMR<256.5; n=271), Group 2 (QFR≥0.8, AMR≥256.5; n=140), Group 3 (QFR<0.8, AMR<256.5; n=77), and Group 4 (QFR<0.8, AMR≥256.5; n=19). The primary endpoint was cardiac death or heart failure readmission within 2 years. RESULTS:Patients with elevated AMR (≥256.5 mmHg·s·m-1) had a significantly increased risk of MACCEs within two years after PCI (P<0.001). Kaplan-Meier analysis showed the lowest survival rate in patients with both QFR<0.8 and AMR≥256.5 mmHg·s·m-1. Multiple linear regression analysis suggested that diabetes (P<0.001), hyperlipidemia (P<0.001), smoking (P<0.014), systemic inflammation response index (P<0.007), and platelet to lymphocyte ratio (P<0.001) were independently associated with elevated AMR levels. Restricted cubic spline regression revealed a non-linear relationship between AMR and MACCEs risk (non-linear P<0.001), and the hazard ratio for MACCEs increased markedly for an AMR beyond the threshold of 259.45 mmHg·s·m-1. CONCLUSIONS:The integrated assessment of QFR and AMR allows effective prediction of MACCEs risk in STEMI patients after PCI, and elevated AMR is an independent predictor of significantly increased risk of MACCEs.

The aim of this study is to evaluate the efficacy and safety of diacylglycerol (DAG) edible oil intervention in patients with chronic metabolic syndrome complicated by asymptomatic hyperuricemia through a multicenter, prospective, double-blind, randomized controlled clinical trial. A multicenter, double-blind, and randomized controlled trial involving 176 patients was designed. All patients with chronic metabolic syndrome complicated by asymptomatic hyperuricemia who meet inclusion and exclusion criteria will be included in the study and will be randomized to either group A or group B. Group A will receive DAG-rich oil (≥ 80

BackgroundBoth the estimated glucose disposal rate (eGDR) and the non-HDL-c/HDL-c ratio (NHHR) are associated with cardiovascular disease risk and prognosis. It is unclear whether assessing eGDR and NHHR together improves CAS progression prediction.MethodsThis large cross-sectional and longitudinal cohort study included 7,360 adults who underwent multiple health check-ups at the Chinese PLA General Hospital from October 2009 to December 2023. The relationships of the eGDR and NHHR with CAS progression were determined through multivariable Cox regression analysis and restricted cubic splines (RCS).ResultsDuring a median follow-up period of 30 months, we included 7,360 participants. The restricted cubic spline curve of the correlation between the eGDR and CAS progression was non-linear. There was a positive linear relationship between the NHHR and CAS progression. When the eGDR was <8.71 (median level) mg/kg/min and the NHHR was >2.89, the risk of CAS progression significantly increased. Subgroup analysis revealed that age significantly altered the correlation. The incorporation of the eGDR and NHHR into the basic model significantly enhanced the usefulness of the model for predicting CAS progression. Furthermore, mediation analysis revealed that the NHHR significantly mediated the impact of the eGDR on CAS progression.ConclusionsThis study revealed that a lower eGDR and higher NHHR are associated with an increased risk of CAS progression. The combined assessment of the eGDR and NHHR can enhance the identification of high-risk populations, which is useful for the implementation of active preventive measures.

The association between the ApoB/ApoA1 ratio and the severity and prognosis of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. This study aims to elucidate the association between the ApoB/ApoA1 ratio and the severity of hepatic steatosis in this population, as well as its connections to all-cause and cause-specific mortality. Data for this research were sourced from Beijing, China, and incorporated from the Third National Health and Nutrition Examination Survey (NHANES III) and the National Death Index (NDI) in the United States. Multivariate logistic regression analysis was employed to examine the relationship between the ApoB/ApoA1 ratio and MAFLD, as well as its severity. Additionally, multivariable Cox regression and restricted cubic spline (RCS) regression models were utilized to evaluate the association between the ApoB/ApoA1 ratio and long-term all-cause and cause-specific mortality among MAFLD patients, including subgroup analyses. After adjusted for confounders, a significant correlation was identified between the ApoB/ApoA1 ratio and both the presence of MAFLD and its severity (all P < 0.05). In mortality analyses, the multivariate Cox regression, also adjusted for confounders, indicated that the ApoB/ApoA1 ratio was significantly linked to overall mortality (HR = 1.52, 95

BACKGROUND:Blood-based cell-free DNA (cfDNA) methylation testing has emerged as a promising approach for multi-cancer early detection (MCED), holding the potential to improve cancer survival rates. However, traditional bisulfite-based methods often encounter sensitivity limitations in detecting early-stage malignancies or certain cancer types. In the INSPECTOR study, we developed a MCED and cancer signal origin (CSO) system specifically designed for early-stage or hard-to-detect cancers, including those of the lung, breast, colorectum, liver, esophagus, stomach, pancreas, and ovary. METHODS:We established a comprehensive methylation marker discovery database (n = 6,342) by integrating public datasets (n = 4,699) and in-house samples (n = 1,643), all processed using human TET (hTET) enzyme-assisted whole-methylome sequencing (GM-seq). This enabled the design of a targeted panel encompassing 155,362 methylated CpG sites. Leveraging hTET-assisted high-depth next-generation sequencing (NGS), our blood test achieved a median unique depth of 1,093×. Multicenter case-control cohorts, including various pathological subtypes, were used for training, validation, and independent validation of MCED and CSO models, and to verify the clinical feasibility. RESULTS:Clinical validation was conducted across multi-center case-control cohorts, including 1,071 participants in the training set, 581 in the validation set, and 824 in the independent validation set. The MCED assay demonstrated robust performance with a specificity of 99.1% and sensitivity of 83.2% in the training set, 99.0% and 81.8% in the validation set, and comparable results in the independent validation set (99.0% specificity, 81.9% sensitivity). Notably, sensitivity reached 65.5% for stage I cancers, 79.7% for stage II, and 71.3% for stages I-II combined. The sensitivities for different cancer types were as follows: esophageal (79.2%), gastric (76.1%), colorectal (86.2%), pancreatic (66.7%), liver (100.0%), lung (72.9%), breast (88.9%), and ovarian (87.9%). The CSO model exhibited strong accuracy, with top-1 cancer origin prediction rates of 87.9% (validation) and 87.4% (independent validation), rising to 95.1% and 94.5% for top-2 predictions, respectively. For stage I cancers specifically, the top-1 accuracy was 85.5%. CONCLUSIONS:These findings underscore the efficacy of the hTET-assisted cfDNA methylation sequencing system across diverse cancer types, particularly in early stages. Enzyme-assisted NGS test of methylated cfDNA thus enhances the clinical utility of non-invasive blood-based screening.

[This corrects the article DOI: 10.3389/fmed.2025.1627246.].

Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95

The integration of predictive, preventive, personalized, and participatory (P4) healthcare advocates proactive intervention, including dietary supplements and lifestyle interventions for chronic disease. Personal profiles include deep phenotypic data and genetic information, which are associated with chronic diseases, can guide proactive intervention. However, little is known about how to design an appropriate intervention mode to precisely intervene with personalized phenome-based data. Here, we report the results of a 3-month study on 350 individuals with metabolic syndrome high-risk that we named the Pioneer 350 Wellness project (P350). We examined: (1) longitudinal (two times) phenotypes covering blood lipids, blood glucose, homocysteine (HCY), and vitamin D3 (VD3), and (2) polymorphism of genes related to folic acid metabolism. Based on personalized data and questionnaires including demographics, diet and exercise habits information, coaches identified 'actionable possibilities', which combined exercise, diet, and dietary supplements. After a 3-month proactive intervention, two-thirds of the phenotypic markers were significantly improved in the P350 cohort. Specifically, we found that dietary supplements and lifestyle interventions have different effects on phenotypic improvement. For example, dietary supplements can result in a rapid recovery of abnormal HCY and VD3 levels, while lifestyle interventions are more suitable for those with high body mass index (BMI), but almost do not help the recovery of HCY. Furthermore, although people who implemented only one of the exercise or diet interventions also benefited, the effect was not as good as the combined exercise and diet interventions. In a subgroup of 226 people, we examined the association between the polymorphism of genes related to folic acid metabolism and the benefits of folate supplementation to restore a normal HCY level. We found people with folic acid metabolism deficiency genes are more likely to benefit from folate supplementation to restore a normal HCY level. Overall, these results suggest: (1) phenome-based data can guide the formulation of more precise and comprehensive interventions, and (2) genetic polymorphism impacts clinical responses to interventions. Notably, we provide a proactive intervention example that is operable in daily life, allowing people with different phenome-based data to design the appropriate intervention protocol including dietary supplements and lifestyle interventions.

Successful development of effective hepatocellular carcinoma (HCC) early diagnosis methods could greatly benefit disease control. Relating to the early detection of liver cancer, multifarious methods exploiting the various genetic aberrations embedded in cell-free DNA have been proposed. Multifaceted feature integration could improve model performance and interpretability. The cohort design and prospective performance validation also significantly affect the model generality. Considering the current demerits, we conducted the PRospective Early Detection In a population at high-risk for Common malignant Tumor (PREDICT) study (clinical trial number NCT04405557), which integrated mainly single nucleotide variants (SNVs) and fragmentation information in model construction on 371 retrospective participants for efficient HCC early detection. The PREDICT model reached 88.41% sensitivity and 95.65% specificity and demonstrated outstanding performance among different clinicopathological populations. Additionally, we integrated the PREDICT model into physical examination packages and prospectively recruited 720 participants from 24 medical institutions. PREDICT model reached 100% sensitivity and 86.7% specificity. Our model reaches a relative equilibrium between cost, performance as well as interpretability and offers an alternative solution for HCC risky individual regular screening and healthy population preventive screening.

Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient’s response to FMT may rely on the capability of the used donor’s microbiota to restore the specific gut disturbances of the patient.

This overview of systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically collate, appraise and synthesize evidence for the treatment of diabetic foot ulcers (DFUs) with the external application of Chinese herbal medicine (CHM). SRs/MAs of external application of CHM for DFUs were collected by searching Cochrane Library, Web of science, CNKI, PubMed, VIP, Embase and Wanfang. Two independent reviewers carried out the literature selection and data extraction. Subsequently, AMSTAR-2 tool, PRISMA, and GRADE system were applied by two reviewers independently to evaluate the methodological quality, reporting quality, and evidence quality of the included studies, respectively. Eight SRs/MAs met the eligibility criteria and were included. According to AMSTAR-2, a very low methodological quality assessment was given to the included SRs/MAs due to the flaws of items 2, 4 and 7. The PRISMA system identified protocol and registration weaknesses, as well as search method weaknesses. With GRADE, no high-quality evidence was identified to support the role of external application of CHM for DFUs, and the quality of evidence for the vast majority of outcomes was rated as low or moderate. In conclusion, low- to moderate-quality evidence supports the promise of external application of CHM for the treatment of DFUs. Due to the limitations of the evidence supporting external application of CHM for DFUs, rigorously designed and larger samples of high-quality studies are needed going forward before broad recommendations can be made.

Background: Traditional Chinese medicines exhibit promising preventive effects on Alzheimer’s disease. Chaihu Shugan San (CSS) is a well-known traditional herbal formula whose several kinds of ingredients have the potential of ameliorating Alzheimer’s disease. The present study aimed to evaluate the effects of CSS on the microbiota–gut–brain axis and cognitive deficits of senescence-accelerated mouse prone 8 (SAMP8) mice as well as investigate the underlying mechanisms.Methods: Thirty 5-month-old SAMP8 mice were randomly divided into the model group (SAMP8), CSS low-dose treatment group (CSSL), and CSS high-dose treatment group (CSSH). Ten SAMR1 mice were used as the normal control, and ten SAMP8 mice treated with donepezil were used as the positive control of cognitive function. CSS was orally administrated to SAMP8 mice for 8 weeks. The Morris water maze test was used to evaluate cognitive function. Histological staining was used to observe neuronal injury and Aβ deposition. Transmission electron microscopy was used to observe the synaptic ultrastructure. 16S rRNA gene analysis was performed to measure the changes in intestinal microbiota.Results: The results showed that CSS significantly improved the learning function and memory deficits of aged SAMP8 mice in the Morris water maze examination. CSS ameliorated neuronal injury, synaptic injuries, and Aβ deposition in the brain of SAMP8 mice. In addition, CSS also significantly improved microbiota composition in terms of elevating Lactobacillus reuteri and decreasing Staphylococcus xylosus in the feces of aged SAMP8 mice.Conclusion: These findings suggested that CSS might have a preventive potential for cognitive deficits in aging through regulating gut microbiota, which paved the way for the application of CSS for prevention and therapeutic purposes for mild cognitive impairment as well as Alzheimer’s disease.

Hypertension is a chronic cardiovascular disease characterized by elevated blood pressure that can lead to a number of complications. There is evidence that the numerous environmental substances to which humans are exposed facilitate the emergence of diseases. In this work, we sought to investigate the relationship between exposure to environmental contaminants and hypertension as well as the predictive value of such exposures. The National Health and Nutrition Survey (NHANES) provided us with the information we needed (2005–2012). A total of 4492 participants were included in our study, and we incorporated more common environmental chemicals and covariates by feature selection followed by regularized network analysis. Then, we applied various machine learning (ML) methods, such as extreme gradient boosting (XGBoost), random forest classifier (RF), logistic regression (LR), multilayer perceptron (MLP), and support vector machine (SVM), to predict hypertension by chemical exposure. Finally, SHapley Additive exPlanations (SHAP) were further applied to interpret the features. After the initial feature screening, we included a total of 29 variables (including 21 chemicals) for ML. The areas under the curve (AUCs) of the five ML models XGBoost, RF, LR, MLP, and SVM were 0.729, 0.723, 0.721, 0.730, and 0.731, respectively. Butylparaben (BUP), propylparaben (PPB), and 9-hydroxyfluorene (P17) were the three factors in the prediction model with the highest SHAP values. Comparing five ML models, we found that environmental exposure may play an important role in hypertension. The assessment of important chemical exposure parameters lays the groundwork for more targeted therapies, and the optimized ML models are likely to predict hypertension.