Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

OBJECTIVE: The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM _2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population. METHODS: We assessed 24,117 individuals along with the annual average PM _2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM _2.5 and smoking frequency on dementia and cognitive impairment. RESULTS: Individuals exposed to the highest PM _2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM _2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM _2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns. CONCLUSION High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM _2.5, and smoking cessation are recommended to promote health.
Humans ; Dementia/etiology* ; Male ; Aged ; Female ; Cognitive Dysfunction/etiology* ; China/epidemiology* ; Particulate Matter/analysis* ; Smoking/epidemiology* ; Air Pollutants/analysis* ; Aged, 80 and over ; Environmental Exposure/adverse effects* ; Prevalence ; Middle Aged

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective To investigate the stent location and effectiveness in different types of iliac vein compression.Methods A retrospective analysis was conducted on patients with left iliac vein compression who underwent stent implantation at our department from June 2021 to December 2023. Based on the location of compression, patients were categorized into high, classical, and low types. The patients’ general information, lesion characteristics, stent details, stent patency, and clinical outcomes were analyzed and followed up.Results A total of 242 patients were included in this study. And 90. 9% (220 cases) were the classical type, 5.4% (13 cases) were the high type, and 3.7% (9 cases) were the low type. There was no significant difference in age distribution, gender ratio and comorbidities among the three groups. The length of inferior vena cava protruding from the high type was significantly longer than that of the classical type[(3.1±0.8) cm vs. (1.6±1.0) cm, P<0.001), but significantly shorter in the low type[(-0.7±2.4) cm vs. (1.6±1.0) cm, P<0.001). The mean follow-up time was (18.0±7.0) months. The stent patency rate was 97.0% at 1 year and 92.8% at 2 years postoperation. The clinical symptoms of the three groups were significantly relieved. No thrombosis was found in right limbs.Conclusions There is a significant difference in the location of the stent tip between classical and non-classical compression types. Complete coverage of lesion by the stent should be the prerequisite for stent placement in treatment of all three types. Small sample, short-term follow-up data suggested that stents can also relieve clinical symptoms and have good patency rate in the high compression type and the low compression type.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Objective:To compare the efficacies of endovascular therapy (EVT) and standard medical therapy in acute ischemic stroke (AIS) patients aged ≥85 years, and analyze the independent influencing factors for poor prognosis of AIS patients after EVT.Methods:Sixty-nine AIS patients aged ≥85 years admitted to Department of Neurology, Xi'an Third Hospital from January 2018 to April 2024, including 40 accepted EVT and 28 accepted standard medicinal therapy, were enrolled. Modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 90 days after onset. General data, prognosis and complications between the EVT group and standard medical therapy group were compared. General data, treatment processes and complications between patients with good prognosis and poor prognosis in the EVT group were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for poor prognosis in AIS patients after EVT.Results:Compared with the standard medical therapy, the EVT group had significantly lower NIHSS score at discharge, greater improvement in NIHSS score (NIHSS score at admission-NIHSS score at discharge), lower mRS score 90 days after onset, higher good prognosis rate, lower mortality rate within 90 days of onset, and longer hospital stay ( P<0.05). In the EVT group, 11 patients (27.5%) had good prognosis and 29 patients (72.5%) had poor prognosis 90 days after onset. Compared with the good prognosis group, the poor prognosis group had significantly higher blood glucose level and lower Alberta Stroke Program Early CT Score (ASPECT) on admission ( P<0.05). Multivariate Logistic regression analysis showed that blood glucose on admission ( OR=2.363, 95% CI: 1.134-4.928, P=0.022) and ASPECT score on admission ( OR=0.273, 95% CI: 0.088-0.854, P=0.026) were independent influencing factors for poor prognosis in AIS patients after EVT. Conclusion:AIS patients aged ≥85 years received EVT have better prognosis compared with those accepted standard medical therapy; these patients with high glucose level and low ASPECT score on admission have poor prognosis.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy in China,with cervical lymph node metastasis being a frequent and critical clinical feature that directly affects patient prognosis and recurrence risk.In recent years,with the rapid increase in the prevalence of overweight and obesity in China,the role of body mass index(BMI)in various tumors has attracted growing attention.This study aimed to investigate the association between overweight and cervical LNM in PTC,analyze sex-specific differences and influencing factors,and provide evidence for precise clinical management.Methods:A retrospective analysis was conducted on the clinicopathologic data of 1 445 patients with classical PTC treated at Xiangya Hospital of Central South University between August 2021 and June 2022.Patients were divided into groups based on the presence or absence of lymph node metastasis.Restricted cubic spline analysis explored the nonlinear relationship between BMI and lymph node metastasis risk.Univariate and multivariate Logistic regression analyses were applied to identify independent risk factors.Furthermore,sex-stratified analysis was performed among overweight patients(BMI≥24 kg/m2)to determine sex-specific risk factors for lymph node metastasis.Results:Among all patients,716(49.6%)had lymph node metastasis.Univariate analysis showed that BMI,sex,age,tumor diameter,multifocality,and extrathyroidal extension were significantly associated with cervical lymph node metastasis in PTC patients(all P<0.05).A nonlinear positive correlation was observed between BMI and lymph node metastasis risk,which was more pronounced in male patients.Additionally,BMI was positively correlated with triglyceride levels and negatively correlated with high-density lipoprotein cholesterol.Sex-stratified analysis revealed that in overweight male patients,younger age(OR=0.954),larger tumor diameter(OR=1.085),and multifocality(OR=2.776)were independent risk factors for LNM;in overweight female patients,younger age(OR=0.943)and larger tumor diameter(OR=1.074)were the main influencing factors.Conclusion:Overweight is closely associated with cervical lymph node metastasis in PTC,and the high-risk factors for LNM differ between male and female overweight patients.Young age,larger tumor size,and multifocality in overweight males,and young age and larger tumors in overweight females indicate a higher risk of metastasis.It is recommended that high-risk populations receive enhanced preoperative evaluation and individualized lymph node dissection strategies to achieve precise treatment and improved risk control.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the feasibility and accuracy of an ultrasound-based transfer learning artificial intelligence model in predicting the malignancy probability of partially cystic thyroid nodules(PCTN).Methods A retrospective analysis was conducted on 246 patients with PCTN who had definitive pathological results and were admitted to Weihai Municipal Hospital,Cheeloo College of Medicine,Shandong University from January 2021 to December 2023.Patients were randomly divided into training and test cohorts at a ratio of 7:3.Ultrasonic image features of PCTN were evaluated,and independent risk factors were identified using multivariate logistic regression analysis,with the area under the curve(AUC)subsequently calculated.Additionally,five different pre-trained models-Inception_v3,EfficientNet,VGG19,ResNet50,and DenseNet121-were selected for transfer learning after data preprocessing using the PyTorch framework in Python.The AUC values of these models were calculated and compared.Results Solid portion greater than 50%,eccentric acute angle,ill-defined margin,spiculated or microlobulated margin,rim calcification,and microcalcification exhibited statistically significant differences(P<0.05)in distinguishing between benign and malignant PCTN.The AUC value derived from these independent risk factors was 0.843.Furthermore,among the five transfer learning models evaluated,the ResNet50 model demonstrated the highest diagnostic efficiency,achieving an AUC value of 0.903 2.Conclusion The ultrasound-based transfer learning artificial intelligence model demonstrated superior performance compared to traditional ultrasound image evaluation methods,enabling accurate prediction of the nature of PCTN and thereby reducing unnecessary ultrasound-guided fine needle biopsies.