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 distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Aortic aneurysm(AA)and aortic dissection(AD)are critical cardiovascular disease emergencies that seriously threaten human life and health.Due to various factors,the progressive reduction of various types of cells,such as smooth muscle cells and endothelial cells in the aortic wall,is an essential mechanism for developing AA and AD.On this basis,AD is induced by mechanical stresses such as hypertension,leading to damaged endothelial rupture or hemor-rhage within the aortic wall.However,AA causes the aortic wall to thin and expand outward in response to stimuli such as prolonged blood flow impingement.At present,increasing evidence shows that various programmed cell death,such as apoptosis,necroptosis,pyroptosis,ferroptosis,copper death,poly ADP-ribose polymerase 1(PARP-1)-dependent cell death,and immunogenic cell death,play essential roles in the pathogenesis of AA and AD.Therefore,understanding the key molecules and pathways in the pathogenesis of AA and AD from the perspective of programmed cell death and searching for inhibitors of various types of programmed death is essential to prevent aortic destruction and disease progression.The review summarizes the roles and research progress of different types of programmed cell death modalities in the development of AA and AD,clarifies the central position of programmed cell death in forming AA and AD,and searches for new thera-peutic methods for the clinic.

Objective To investigate the correlation between hemoglobin A1c(HbA1c)levels and excessive daytime sleepiness(EDS)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 132 T2DM patients and 40 healthy people(NC group)who were treated in the outpatient department of Nanjing Meishan Hospital from December 2020 to December 2022 were selected.General clinical data of the subjects were collected,and their Epworth sleepiness scale(ESS)scores,Pittsburgh sleep quality index(PSQI),and apnea-hypopnea index(AHI)were measured.Based on ESS scores,T2DM patients were divided into simple T2DM group(ESS score<9,n=99)and EDS group(ESS score≥9,n=33)according to ESS score.The baseline data were compared for each group.Spearman correlation analysis and multivariate logistic regression model were used to evaluate the correlation between HbA1c levels and EDS.The receiver operating characteristic(ROC)curve was used to calculate the area under the curve(AUC)to evaluate the predictive value of HbA1c levels for EDS.Results HbA1c,fasting plasma glucose,AHI index and PSQI score in EDS group were higher than those in T2DM and NC group(P<0.05).Spearman correlation analysis showed that ESS score was positively correlated with HbA1c in T2DM patients(P<0.05).Multivariate logistic regression analysis revealed that elevated HbA1c levels emerged as a significant and independent risk factor for the onset of EDS.The ROC curve indicated that the AUC of HbA1c for predicting EDS was 0.736.Conclusions There is an independent positive correlation between HbA1c levels and EDS in T2DM patients,which provides clues for early identification and treatment of EDS in clinical practice.

Objective:To develop a multi-parameter diagnostic model for pediatric McCune-Albright syndrome(MAS) using machine learning techniques based on laboratory data from MAS patients, with the goal of providing a rapid and reliable auxiliary diagnostic tool for clinical practice.Methods:In this retrospective study, 232 children diagnosed with MAS at the Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from March 2023 to November 2024 were enrolled as the positive group. After removing duplicate or missing data, 119 cases were finally selected for statistical analysis as the positive group. Meanwhile, 113 children with normal physical examinations during the same period were selected as the control group. The clinical manifestations of the classic " triad" in the positive group were documented. Fasting serum samples were obtained from both groups at 8: 00 AM for laboratory testing, including bone metabolism-related and hormone-related indicators, which served as candidate features. Baseline descriptive analysis was conducted on the hormone-related indicators. For the bone metabolism indicators, six machine learning models—support vector machine(SVM), XGBoost, decision tree, random forest, Logistic regression, and K-nearest neighbor(KNN)—were constructed using R software. XGBoost subgroup analysis was performed based on the triad symptoms. The contribution of individual features to model predictions was visualized using SHAP diagrams. Results:SHAP visualization indicated that age, serum phosphorus, osteocalcin, and β-C-terminal cross-linked telopeptide of type Ⅰ collagen had the greatest average impact on model predictions. Among the six models, the SVM model achieved the highest diagnostic performance, with a sensitivity of 0.742 9, a specificity of 0.909 1, and an area under the curve (AUC) of 0.917.Conclusion:This study demonstrates that machine learning models, based on data from the positive patients and normal controls, can effectively distinguish MAS patients from healthy controls. The diagnostic model developed offers clinicians a valuable tool for early detection of MAS in children, contributing to earlier diagnosis, timely intervention, and improved clinical management.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Objective:To investigate the imaging characteristics of fibrous dysplasia(FD) in children with McCune-Albright syndrome(MAS) and the correlation between FD severity and bone metabolism markers, so as to provide a basis for clinical diagnosis and treatment.Methods:A total of 46 children(38 females and 8 males) with MAS with FD who were admitted to the Department of Pediatrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2016 were included in the retrospective study, and all of them met the diagnostic criteria for either the MAS triad or dual manifestations. The extent and characteristics of FD lesions were evaluated by imaging analysis(X-ray and CT). The distribution of café-au-lait spots and endocrine abnormalities were recorded. The serum bone metabolism levels [total procollagen type 1 amino-terminal propeptide(TP1NP), osteocalcin, β-C-terminal telopeptide(β-CTX), alkaline phosphatase(ALP)], and other related indicators such as calcium, phosphorus, magnesium, and fibroblast growth factor(FGF23) levels were detected, and the association between FD severity and indicators was evaluated by Spearman correlation analysis.Results:Among the 46 children, there were 24 cases of triad(FD+ café-au-lait spots + precocious puberty) and 22 cases of dual manifestations(11 cases of FD+ café-au-lait spots or precocious puberty). The age of onset of FD patients(24 cases) with bilateral long bones and skull FD was significantly earlier than that in the unilateral FD group [(3.33±1.34)years vs(5.26±2.34)years, P<0.01], and all of them had extensive café-au-lait spots across the midline. Polyostotic FD accounted for 71.7%(33/46), mainly cystic expansive lesions involving the femur(30 cases) and tibia(24 cases), and skull FD(25 cases) mostly showed ground-glass changes; Monostotic FD(13 cases) was more common in the skull(5 cases) and phalanges(5 cases). FD severity was significantly positively correlated with ALP( ρ=0.554, P=0.002), and negatively correlated with serum phosphorus( ρ=-0.522, P=0.006). All 6 children with severe fractures had FGF23-mediated hypophosphatemia [(1.03±0.12) mmol/L vs control(1.52±0.15) mmol/L, P=0.003]. Conclusions:Extensive café-au-lait spots(across the midline) in children with MAS are strongly associated with early-onset polyostotic FD; FD severity was strongly associated with bone turnover markers(TP1NP, β-CTX, ALP) and FGF23-mediated hypophosphatemia. Early comprehensive skeletal assessment and regular FGF23 monitoring are recommended for children with MAS presenting with extensive cutaneous café-au-lait spots.