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.

Aim To investigate the possible mechanism of the myocardial protective effect of Danzhi Jiangtang capsules(DJC)on db/db mice based on NLRP3 in-flammasome-mediated pyroptosis.Methods The db/db mice were randomly divided into the model group,DJC low,medium,and high dose groups,and the met-formin group,and the db/m mice were taken as the blank group.The administration lasted for eightweeks.At the end of drug administration,blood glucose,blood lipids,cardiac enzymes and inflammatory factors were detected in each group of mice.HE and Masson stai-ning was performed to observe the morphology and fi-brosis of myocardial tissue.TUNEL staining was per-formed to detect apoptosis.RT-qPCR was performed to detect the mRNA expression of ANP,BNP and β-MHC,and Western blot was performed to detect the protein expression of NLRP3,ASC,caspase-1,cleaved-caspase-1,GSDMD and GSDMD-NT in myocardial tis-sue.Results DJC could alleviate myocardial patho-logical damage,reduce collagen deposition and apopto-sis,reduce the levels of blood glucose,blood lipid,myo-cardial enzyme and inflammatory factors in db/db mice.DJC could reduce the mRNA expressions of ANP,BNP and β-MHC,and the protein expressions of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissues.Conclusion DJC attenuates myocardial injury in db/db mice,prob-ably by inhibiting the activation of NLRP3 inflamma-somes,attenuating cardiomyocyte pyroptosis,and amel-iorating the inflammatory state.

AIM To evaluate the quality consistency of Tongmai Granules,Tongmai Tablets,Tongmai Capsules and Tongmai Oral Liquid.METHODS The HPLC fingerprints were established,after which the contents of danshensu,protocatechuic aldehyde,3'-hydroxy puerarin,puerarin,puerarin apioside,daidzin,ferulic acid,salvianolic acid B and salvianolic acid A were determined,and cluster analysis and principal component analysis were adopted in the quality analysis from the perspective of daily intake.RESULTS There were 21 common peaks in the fingerprints for 39 batches of samples with the similarities of 0.765-0.997.Various batches of samples were clustered into 5 categories,2 principal components demonstrated the accumulative variance contribution rate of 83.53％ .The daily intakes of various constituents in different dosage forms exhibited obvious differences,especially for that of salvianolic acid B,which were low in tablets and capsules,and their heterogeneities existed among the same dosage forms.CONCLUSION This simple and accurate method can provide a reference for the quality evaluation of Tongmai preparations from different manufacturers.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To explore the influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial internal carotid artery(ICA)stenosis and to construct a nomogram prediction model.Methods This study retrospectively and consecutively enrolled patients diagnosed with unilateral moderate-to-severe extracranial ICA stenosis and exhibited indications for carotid endarterectomy(CEA)hospitalized in the Department of Neurosurgery at the First Affiliated Hospital of Soochow University,between August 2019 and September 2024.The patients were divided into a stroke group and a non-stroke group,based on their clinical presentation and head MRI results.Baseline characteristics and clinical data including age,sex,body mass index,blood pressure(systolic and diastolic pressure[＜140 mmHg,140-＜160 mmHg,≥160 mmHg]),hypertension,diabetes,smoking and alcohol consumption history,use of statin and antiplatelet medication,fasting blood glucose,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),total cholesterol(TC)were collected and ratios between LDL-C/HDL-C,TG/HDL-C,non-HDL-C(calculated according to equation:non-HDL-C=TC-HDL-C),and non-HDL-C/HDL-C(nHHR)were calculated based on aforementioned data.The clinical and baseline data were then compared between two groups.Imaging data included side of carotid artery stenosis(identified through neck vascular ultrasound,CT angiography and/or DSA),degree of carotid stenosis(with 50％-69％categorized as moderate stenosis,and,70％-99％as severe stenosis),plaque echogenicity(predominantly low,medium or high),plaque calcification(surface and basal calcification),plaque ulceration(exists or not),bilateral middle cerebral artery(MCA)hemodynamic parameters measured by transcranial Doppler ultrasound(including,mean flow velocity[Vm],peak systolic velocity[Vs],end-diastolic velocity[Vd]),and the pulsatility index(PI,calculated via formula:PI=[Vs-Vd]/Vm).The hemodynamic parameter differences(△Vm,△Vs,△Vd,△PI)between the healthy and affected MCA were calculated.The baseline,clinical and imaging data with P＜0.05 in univariate analysis were included in multivariate Logistic regression analysis using forward stepwise selection to identify influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis,and a nomogram prediction model was then constructed base on the analyzed results.Receiver operating characteristic curves were plotted,and the area under the curve(AUC)was calculated to evaluate the predictive performance of the nomogram.Delong's test was used to compare AUC differences between single indicators and the combined model.Results A total of 166 patients with unilateral moderate-to-severe extracranial ICA stenosis and CEA indication were included.In which,99 patients were in the stroke group and 67 patients were in the non-stroke group.The stroke group had a significantly higher proportion of hypertension patients(78.8％[78/99]vs.59.7％[40/67],P=0.008),higher systolic blood pressure([152±15]mmHg vs.[137±18]mmHg,P＜0.01),higher diastolic blood pressure([84±10]mmHg vs.[80±10]mmHg,P=0.042),higher TG(1.33[0.95,1.77]mmol/L vs.1.10[0.87,1.48]mmol/L,P=0.019),higher TG/HDL-C(1.35[0.97,2.08]vs.1.07[0.81,1.52],P=0.003),and higher nHHR(2.89[2.25,3.61]vs.2.48[1.93,3.27],P=0.027)than the non-stroke group.The HDL-C was significantly lower in the stroke group(0.96[0.80,1.15]mmol/L vs.1.03[0.91,1.16]mmol/L,P=0.014).Statistically significant differences were also observed in the distribution of systolic blood pressure between the groups(P＜0.01).No significant differences were found in other clinical data(all P＞0.05).The proportion of patients with carotid plaque ulceration was higher in the stroke group(35.4％[35/99]vs.16.4％[11/67],P=0.007),while stenosis side,stenosis degree,plaque echogenicity,and plaque calcification type showed no significant differences between the groups(all P＞0.05).△Vm(19[4,32]cm/s vs.10[-3,21]cm/s,P=0.001),△Vs(32[9,55]cm/s vs.24[3,40]cm/s,P=0.005),and △Vd(10[-1,19]cm/s vs.6[-3,12]cm/s,P=0.006)were significantly higher in the stroke group.No significant difference was found in △PI(P=0.076).Multivariate Logistic regression analysis identified high systolic blood pressure(OR,1.063,95％CI 1.036-1.090,P＜0.01),high TG/HDL-C(OR,2.802,95％CI 1.551-5.061,P=0.001),high △Vm(OR,1.032,95％CI 1.010-1.055,P=0.004),and plaque ulceration(OR,2.777,95％CI 1.123-6.871,P=0.027)as independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.Systolic blood pressure,TG/HDL-C,△Vm and plaque ulceration were involved in the construction of a combined predictive model for ischemic stroke in the targeted patient group(with unilateral moderate-to-severe extracranial ICA stenosis).The AUC of the combined prediction model was 0.828(95％CI 0.765-0.892,P＜0.01),which was significantly higher than the predictive efficacy of any single factor(all P＜0.01).Conclusions High systolic blood pressure,high TG/HDL-C ratio,high △Vm,and plaque ulceration are independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.The nomogram prediction model based on these factors demonstrates good predictive value for assessing ischemic stroke risk in this patient population.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.