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.

Abnormal synaptic plasticity is an early pathological feature of Alzheimer disease (AD). Synaptic damage and dysfunction initiate neuronal degeneration and death, ultimately leading to cognitive impairment. Traditional Chinese medicine (TCM) can effectively ameliorate cognitive dysfunction through multitarget regulation of synaptic plasticity. This review summarizes the mechanisms by which TCM, including active components, single herbs, and classical formulas, modulates synaptic plasticity, offering new insights for future research and clinical applications. Relevant experimental studies published between 2020 and 2024 were retrieved from major databases, including China National Knowledge Infrastructure, the National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and Web of Science. Network pharmacology and bioinformatics approaches were used to predict the therapeutic effects and mechanisms of TCM on AD-related synaptic plasticity. In total, 15 TCM single herbs and 11 TCM formulas were identified as enhancing AD-related synaptic plasticity. Additionally, 15 active ingredients targeting synaptic plasticity in AD were retrieved from TCM databases over the past decade. This review provides novel perspectives and strategic directions for future AD research and therapeutic development.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Objective To observe the association between afterschool physical exercise and sleep quality among preschool children,and to explore the proper afterschool physical exercise model for better sleep quality.Methods A cross-sectional study was conducted.From Apr to Jun 2024,a total of 1 430 children from three public kindergartens in Minhang district were enrolled to participate in the survey.Parents were invited to complete the basic sociodemographic information,afterschool physical exercise information and the Children's Sleep Habits Questionnaire.One-way ANOVA and linear mixed effects models were used to explore the relationship between afterschool exercise and sleep quality.Results A total of 1 430 questionnaires were sent out and 1 384 were recovered with a recovery rate of 96.78%.Among them 1 366 were valid,with an effective rate of 95.52%.The average age of the children was(5.19±0.87)years old with gender ration of 1.07∶1(male:female).The prevalence of poor sleep quality was 80.60%(regarding a CSHQ total score>41 as cutoff).A one-way ANOVA indicated that time on afterschool physical exercise was significantly associated with sleep duration,Night waking,and sleep onset delay(P<0.05).After adjusting for age,gender,the only child or not,main caregiver,and parental education and occupation,linear mixed effects models showed that engaging in afterschool physical activity for at least 180 mins per week has a statistically significant predictive effect on sleep duration scores(β=-0.50,z=-4.52,95%CI:-0.72,-0.28,P<0.001),night waking scores(β=-0.16,z=-2.34,95%CI:-0.29,-0.02,P=0.020),and sleep onset delay scores(β=-0.14,z=-2.35,95%CI:-0.26,-0.02,P=0.019).Conclusion Afterschool exercise was significantly associated with sleep quality among preschool children in Minhang district of Shanghai.The time≥180 min on afterschool exercise per week in preschool children was significantly positively associated with maintaining sleep duration,reducing night wakings and shortening the latency to fall asleep.The habit of afterschool exercise and the time on afterschool exercise should be emphasized by parents and the society to improve sleep quality among preschool children.

Objective:To explore the types and characteristics of self-management behaviors among stroke patients, as well as to analyze the influencing factors associated with these different types, providing a reference for developing intervention programs aimed at enhancing self-management behaviors in stroke patients.Methods:This study adopted a cross-sectional survey design. The stroke inpatients were selected through convenience sampling from the Department of Neurology at Huashan Hospital, Fudan University between October 2023 and August 2024. Data collection was conducted using the following instruments: the General Information Questionnaire, Stroke Self-Management Behavior Rating Scale, Self-Efficacy for Managing Chronic Disease 6-Item Scale, Stroke Health Knowledge Questionnaire, Social Support Rating Scale, Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, and the modified Rankin Scale. Stroke patients' self-management behaviors were categorized using systematic cluster analysis, and disordered multi-class Logistic regression was employed to identify the influencing factors associated with each category.Results:Finally, 210 stroke patients were enrolled, there were 148 males and 62 females, aged (60.82 ± 13.05) years. The total score of self-management behavior in stroke patients was (144.18 ± 23.24) points, with a score rate of 56.54%. Systematic cluster analysis identified four distinct self-management behaviors patterns: consistent implementers (25.71%, 54/210); unrealistically optimistic(54.76%, 115/210); optimistically proactive (13.81%, 29/210); and passive and resigned (5.71%, 12/210). Disordered multi-class Logistic regression analysis indicated that higher scores in stroke-related health knowledge were associated with a greater likelihood of being categorized as stable practice type and optimistic proactive type ( OR=1.130, 1.254, both P<0.05). Conversely, increased levels of depression correlate with a higher probability of being classified as passive waiting type ( OR=0.684, 0.722, 0.540, all P<0.05). Additionally, lower modified Rankin Scale scores were linked to an increased tendency to fall into the categories of stable practice type and blind optimism type ( OR=19.759, 23.148, both P<0.05). Conclusions:The self-management behaviors of stroke patients are generally suboptimal and exhibited distinct classification features. Significant differences are observed in stroke health knowledge, depression, and the modified Rankin Scale scores among the four patient types. Healthcare professionals should tailor intervention measures to the characteristics of each type to enhance patients' self-management capacity.

The effective integration of ideological and political education into medical courses is one of the most important aspects of medical teaching reform and a key approach to fostering students'moral character.Based on the Outcomes-Based Education(OBE)philosophy,this article focuses on the learning outcomes of Medical Immunology ideological and political education,integrating relevant ideological and political elements with modular teaching content to form a themed"Medical Immunology Ideological and Politi-cal"teaching goal with distinctive features of Medical Immunology.Through a blended learning model of online and offline teaching methods,students are guided to learn modular teaching content.This study creatively integrates Medical Immunology theory with ideo-logical and political elements,carries out"Medical Immunology Ideological and Political"through professional knowledge,and achieves the goal of subtle and deep-seated ideological and political education.Moreover,it effectively improves students'comprehensive learning and application abilities,enabling them to apply what they have learned.

Objective To explore the relationship between triglyceride-glucose(TyG)index and hypertension in patients with cerebral hemorrhage.Methods A total of 1718 patients with cere-bral hemorrhage admitted to our hospital from January,2013 to May,2023 were enrolled in this study.According to the TyG index quartile,437 cases were assigned into Q1 group(≤8.375),424 cases into Q2 group(TyG index 8.376～8.737),429 cases into Q3 group(TyG index 8.738～9.087),and 428 cases into Q4 group(≥9.088).The general clinical data were compared in the four groups.Logistic regression analysis was used to study the correlation between TyG index and hy-pertension.Results There were significant differences among the four groups in terms of age,hy-pertension,diabetes,SBP,DBP,TC,TG,HDL-C,LDL-C,FBG,glycated hemoglobin and TyG in-dex(P＜0.05,P＜0.01).Logistic regression analysis showed that when the TyG index was a con-tinuous variable,it was significantly correlated with the risk of hypertension(OR=1.999,95％CI:1.393-2.869,P=0.001).When the index was used as a categorical variable,with Q1as a ref-erence,TyG index in Q3 and Q4 was associated with an increase in OR of hypertension(OR=1.869,95％CI:1.220-2.865,P=0.004;OR=1.844,95％CI:1.125-3.020,P=0.015).After ad-justing cofounders,the association of TyG index and risk of hypertension was stronger in the fe-males(OR=2.618,95％CI:1.312-5.221,P=0.006)than the males(OR=1.783,95％CI:1.151-2.761,P=0.010),and in the patients ≥65 years old(OR=3.277,95％CI:1.600-6.741,P=0.001)than those＜65 years old(OR=1.782,95％CI:1.076-2.949,P=0.025).Conclusion TyG index is closely associated with hypertension in patients with cerebral hemorrhage,especially in women and elderly.

Objective To investigate the risk factors for acute respiratory failure in immunocompromised patients with Pneumocystis jirovecii pneumonia(PJP).Methods Clinical data of 123 immunocompromised patients complicated with PJP hospitalized at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2021 to December 2023 were retrospectively collected and analyzed.SPSS 22.0 statistical software package was used to perform multivariate binary logistic regression analysis to identify risk factors for acute respiratory failure in PJP patients.Results Among the 123 PJP patients,77 were HIV-positive,and 46 were HIV-negative.HIV-negative PJP patients were more likely to have comorbidities such as hypertension(P＜0.001),diabetes mellitus(P＜0.001),coronary heart disease(P=0.034),chronic kidney disease(P＜0.001),chronic liver disease(P=0.019),chronic lung disease(P=0.011),and malignant tumor(P＜0.001).They were also more prone to respiratory failure(P＜0.001)and ICU admission(P＜0.001).The HIV-positive patients had significantly lower CD4+T lymphocyte counts and albumin levels(P＜0.001).Forty patients developed acute respiratory failure,and six patients died.Multivariate analysis showed that high neutrophil-to-lymphocyte ratio(NLR)(P=0.031),non-HIV infection(P=0.002),and concomitant infections with other pathogens(P＜0.001)were independent risk factors for incidence of respiratory failure.ROC curve analysis revealed that the area under the curve(AUC)was 0.686(0.584,0.789)for non-HIV infection,0.731(0.637,0.826)for concomitant infections with other pathogens,0.648(0.546,0.750)for NLR.The predicted probability was 0.845(0.778,0.912).Conclusions Non-HIV infection,high NLR,and concomitant infections with other pathogens are independent risk factors for incidence of respiratory failure in PJP patients.The panel combining these factors provides a higher predictive value for respiratory failure.Timely assessment of patient condition and early treatment are vital for better outcomes.

Objective To investigate the application value of systemic inflammatory response index(SIRI)in patients with acute-on-chronic liver failure(ACLF)and co-infection.Methods A retrospective analysis was performed for the clinical data of 579 ACLF patients with co-infection who were diagnosed and treated in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to March 2016,including demographic features,laboratory markers,and complications,and SIRI,Model for End-Stage Liver Disease(MELD)score,MELD combined with serum sodium concentration(MELD-Na)score,and Child-Pugh score were calculated.According to the results of follow-up on day 90,the patients were divided into survival group with 210 patients and death group with 369 patients.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test were used for comparison of categorical data between two groups.The binary logistic regression analysis was used to investigate the independent risk factors for 90-day death.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to assess the performance of SIRI,MELD-Na score,and Child-Pugh score in predicting the prognosis of ACLF patients with co-infection.The Kaplan-Meier survival analysis was performed based on the optimal cut-off value of SIRI.Results Among the 597 ACLF patients with co-infection,384(66.32%)had HBV-related ACLF and 114(19.69%)had alcohol-related ACLF;as for the main infection sites,316(54.58%)had abdominal infection and 133(22.97%)had pulmonary infection;the 90-day mortality rate was 63.73%.The multivariate logistic regression analysis showed that SIRI(odds ratio[OR]=1.177,95%confidence interval[CI]:1.117-1.239,P<0.05),blood ammonia(OR=1.009,95%CI:1.001-1.018,P<0.05),MELD-Na score(OR=1.047,95%CI:1.016-1.080,P<0.05),Child-Pugh score(OR=1.351,95%CI:1.054-1.730,P<0.05),age(OR=1.045,95%CI:1.021-1.070,P<0.05),comorbidity with hepatic encephalopathy(OR=2.269,95%CI:1.305-3.946,P<0.05),and comorbidity with acute kidney injury(OR=1.730,95%CI:0.990-3.023,P<0.05)were independent risk factors for 90-day death in ACLF patients with co-infection.The Pearson correlation analysis showed that SIRI was positively correlated with MELD-Na score(r=0.282,P<0.001)and Child-Pugh score(r=0.168,P<0.001).SIRI,MELD-Na score,and Child-Pugh score had an AUC of 0.855,0.734,and 0.690,respectively,in predicting 90-day death,and SIRI had a higher predictive efficiency than MELD-Na score and Child-Pugh score(Z=4.922 and 6.289,both P<0.001),with a sensitivity of 76.7%and a specificity of 82.9%.In addition,SIRI combined with MELD-Na score or Child-Pugh score improved the predictive efficiency of MELD-Na score(0.854 vs 0.734,Z=6.899,P<0.001)and Child-Pugh score(0.858 vs 0.690,Z=8.725,P<0.001).The patients with high SIRI(≥4.08)had a 90-day survival rate of 11.29%(36/319),which was significantly lower than that in the patients with low SIRI(<4.08)(χ2=225.24,P<0.001).Conclusion SIRI is an independent risk factor for death in ACLF patients with co-infection and has a good clinical value in predicting prognosis,with the advantages of convenience and low costs.