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.

High-quality clinical research represents the scientific foundation for generating credible medical evidence， guiding evidence-based practice， and optimizing public health strategies. The responsible conduct of research by clinical researchers serves as the core guarantee of research quality. Any act of research misconduct will not only result in the waste of research resources and damage the reputation of relevant individuals and institutions， but also undermine the validity of research evidence， mislead evidence-based medical practice， raise risks for public health decision-making， and ultimately impede the progress of medical innovation. Based on the framework of reinforcement theory， this paper elaborated on the internal correlation between reinforcement theory and the shaping of responsible conduct of research among clinical researchers， and demonstrated the necessity of shaping responsible conduct of research in the new context. It also summarized practical challenges encountered in such shaping， such as utilitarian-oriented research evaluation， complex conflicts of interest， inadequate review and supervision， constrained research resources， and insufficient education on responsible conduct of research. It further proposed countermeasures that were conducive to shaping the responsible research conduct of clinical researchers. These encompassed reconstructing the orientation of performance evaluation， dynamically managing risks arising from conflicts of interest， implementing precise constraints via ethical supervision， arranging tiered resource support， and internalizing cultural recognition of responsible research conduct.

Objective To explore the chain-mediating effect of anxiety and maladaptive coping strategies on perceived social support and post-traumatic stress disorder(PTSD)in primary caregivers of children with acute leukemia.Methods Two hundred primary care-givers of children with acute leukemia treated in the Pediatric Hematology Department of Shengjing Hospital of China Medical University between September 2022 and April 2023 were selected.A general information questionnaire,Perceived Social Support Scale,Self-Rating Anxiety Scale,Trait Coping Style Questionnaire,and Post-Traumatic Stress Disorder Checklist-Civilian Version were used for the survey.Pearson's correlation analysis was performed to determine the relationships between anxiety,maladaptive coping,perceived social sup-port,and PTSD.The chain-mediating effect was determined by structural equation modeling using Analysis of Moment Structures software and the Bootstrap method.Results PTSD was negatively correlated with perceived social support(r=-0.179,P＜0.05)and positively correlated with anxiety and maladaptive coping(r=0.762,P＜0.01;r=0.423,P＜0.01).Anxiety and maladaptive coping had chain-me-diating roles in the relationship between perceived social support and PTSD.Conclusion Perceived social support can indirectly affect the PTSD level of a caregiver through the chain-mediating effect of anxiety and maladaptive coping strategies.In clinical practice,enhancing caregivers perception of social support can alleviate anxiety,promote positive coping strategies,reduce negative coping strate-gies,and effectively reduce the risk of developing PTSD.

Objective To explore the chain-mediating effect of anxiety and maladaptive coping strategies on perceived social support and post-traumatic stress disorder(PTSD)in primary caregivers of children with acute leukemia.Methods Two hundred primary care-givers of children with acute leukemia treated in the Pediatric Hematology Department of Shengjing Hospital of China Medical University between September 2022 and April 2023 were selected.A general information questionnaire,Perceived Social Support Scale,Self-Rating Anxiety Scale,Trait Coping Style Questionnaire,and Post-Traumatic Stress Disorder Checklist-Civilian Version were used for the survey.Pearson's correlation analysis was performed to determine the relationships between anxiety,maladaptive coping,perceived social sup-port,and PTSD.The chain-mediating effect was determined by structural equation modeling using Analysis of Moment Structures software and the Bootstrap method.Results PTSD was negatively correlated with perceived social support(r=-0.179,P＜0.05)and positively correlated with anxiety and maladaptive coping(r=0.762,P＜0.01;r=0.423,P＜0.01).Anxiety and maladaptive coping had chain-me-diating roles in the relationship between perceived social support and PTSD.Conclusion Perceived social support can indirectly affect the PTSD level of a caregiver through the chain-mediating effect of anxiety and maladaptive coping strategies.In clinical practice,enhancing caregivers perception of social support can alleviate anxiety,promote positive coping strategies,reduce negative coping strate-gies,and effectively reduce the risk of developing PTSD.

In surgical diagnosis and treatment,the perioperative period is a comprehensive diagnosis and treatment process,including the rational application of antibiotics,nutrition management,pain management,blood pressure,blood sugar man-agement,and other processes.Perioperative pharmaceutical care has become one of the innovative fields of pharmaceutical care.In order to ensure the work and service quality of perioperative pharmaceutical care,the preparation team of perioperative pharmaceu-tical care standards takes scientific,universal,and practical principles as the basic principles,reviews the key points and difficul-ties from the three aspects of relevant national policy documents,relevant domestic and foreign standards and norms,and literature analysis,and combines the actual situation of perioperative pharmaceutical care.This pharmaceutical care standard was formulated after several rounds of opinion solicitation and expert argumentation.This paper analyzes the key contents of the standard,inclu-ding the basic requirements,service process,quality control,and evaluation and improvement of perioperative pharmaceutical care,so as to provide reference suggestions for medical structure managers and pharmacists who carry out perioperative pharma-ceutical care to deeply understand and practice this standard,so as to improve perioperative pharmaceutical care.

The problem of drug resistance resulting from the long-term use of antimicrobials is a serious threat to global health,and the emergence of multidrug-resistant bacteria,in particular,has greatly limited therapeutic op-tions.Therefore,the development of new or alternative antimicrobial agents has become an urgent need.Antimi-crobial peptides(AMPs)have been regarded as good alternatives to antibacterial drugs due to their strong antibac-terial activity and unique mechanism of action.At present,some AMPs have completed preclinical studies on drug-resistant bacterial infections and entered the clinical trial stage,while their stability and targeting have been signifi-cantly improved through the optimisation of amino acid modification,nano-delivery system and other technolo-gies,which have gradually become a research hotspot in this field.Therefore,this paper discusses the importance of AMPs in bacterial drug resistance from the biological properties of AMPs,the mechanism of regulating bacteri-al drug resistance and the application of AMPs in the treatment of drug-resistant bacterial infections,with a view to providing a reference for the development of drugs against drug-resistant bacteria and clinical application.

The problem of drug resistance resulting from the long-term use of antimicrobials is a serious threat to global health,and the emergence of multidrug-resistant bacteria,in particular,has greatly limited therapeutic op-tions.Therefore,the development of new or alternative antimicrobial agents has become an urgent need.Antimi-crobial peptides(AMPs)have been regarded as good alternatives to antibacterial drugs due to their strong antibac-terial activity and unique mechanism of action.At present,some AMPs have completed preclinical studies on drug-resistant bacterial infections and entered the clinical trial stage,while their stability and targeting have been signifi-cantly improved through the optimisation of amino acid modification,nano-delivery system and other technolo-gies,which have gradually become a research hotspot in this field.Therefore,this paper discusses the importance of AMPs in bacterial drug resistance from the biological properties of AMPs,the mechanism of regulating bacteri-al drug resistance and the application of AMPs in the treatment of drug-resistant bacterial infections,with a view to providing a reference for the development of drugs against drug-resistant bacteria and clinical application.

Objective:s To investigate the risk factors for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in patients with acute carbon monoxide poisoning (ACOP) and to develop predictive models based on machine learning algorithms.Methods:Patients with ACOP hospitalized at the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2024 were included, with the occurrence of DEACMP as the outcome measure. The dataset was randomly divided into training and validation sets at a ratio of 7:3. Lasso regression was used to select features influencing the outcome in training sets. Nine machine learning models—including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM)—were constructed. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) calculated for each model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was applied to evaluate clinical utility. The SHapley Additive exPlanations (SHAP) method was employed to visualize and interpret the best-performing model.Results:A total of 264 ACOP patients were included, of whom 54 (20.5%) developed DEACMP. Lasso regression identified eight key feature variables. Based on these factors, predictive models were constructed, showing good AUC stability across the nine machine learning models in both training (0.92–0.99) and validation sets (0.85–0.91). The RF model performed best, with an AUC of 0.99 in the training set and 0.90 in the validation set; its calibration curve and DCA curve also demonstrated excellent performance. SHAP analysis of the RF model revealed the importance ranking of factors from highest to lowest as follows: Glasgow Coma Scale (GCS) score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, diastolic blood pressure (DBP), and drinking history.Conclusions:The RF model exhibited the highest predictive performance for DEACMP occurrence in ACOP patients. The influencing factors, ranked in order of importance from highest to lowest, are as follows: GCS score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, DBP, and drinking history.

In surgical diagnosis and treatment,the perioperative period is a comprehensive diagnosis and treatment process,including the rational application of antibiotics,nutrition management,pain management,blood pressure,blood sugar man-agement,and other processes.Perioperative pharmaceutical care has become one of the innovative fields of pharmaceutical care.In order to ensure the work and service quality of perioperative pharmaceutical care,the preparation team of perioperative pharmaceu-tical care standards takes scientific,universal,and practical principles as the basic principles,reviews the key points and difficul-ties from the three aspects of relevant national policy documents,relevant domestic and foreign standards and norms,and literature analysis,and combines the actual situation of perioperative pharmaceutical care.This pharmaceutical care standard was formulated after several rounds of opinion solicitation and expert argumentation.This paper analyzes the key contents of the standard,inclu-ding the basic requirements,service process,quality control,and evaluation and improvement of perioperative pharmaceutical care,so as to provide reference suggestions for medical structure managers and pharmacists who carry out perioperative pharma-ceutical care to deeply understand and practice this standard,so as to improve perioperative pharmaceutical care.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.