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.

The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.

OBJECTIVE To explore the current status,etiological characteristics and risk factors for nosocomial in-fections in the patients who are treated with extracorporeal membrane oxygenation(ECMO)so as to provide bases for treatment and prevention of nosocomial infections in the ICU patients treated with ECMO.METHODS The clinical data were retrospectively collected from the patients who were treated with ECMO in the ICU of Xinyang Central Hospital from Jan.2021 to Dec.2023.The patients were divided into the infection group and the non-infec-tion group according the status of nosocomial infection during the ECMO treatment period.The constituent ratios of pathogens isolated from the patients with infections were recorded,and multivariate logistic regression analysis was performed for independent risk factors for the ECMO-related nosocomial infections.RESULTS Of 86 patients who were finally enrolled in the study,33(38.37％)had nosocomial infections.Totally 54 strains of pathogens were isolated from the patients with the infections,43(79.63％)of which were gram-negative bacteria,7(12.97％)were gram-positive bacteria,and 4(7.41％)were fungi.There were 36(66.67％)strains of multi-drug-resistant organisms(MDROs)among the 54 strains of pathogens,and 27(81.82％)patients were detected with MDROs.Among the ECMO patients with postoperative nosocomial infections,21(63.64％)cases had pul-monary infections,8(24.24％)cases had bloodstream infection,and 4(12.12％)had urinary system infections.Multivariate logistic analysis showed that the high blood glucose level at the beginning of treatment with ECMO,long duration of ECMO treatment and long time of central venous catheter indwelling were the independent risk factors for the nosocomial infections in the patients treated with ECMO(P＜0.05).CONCLUSION The isolation rate of gram-negative bacteria is relatively high among the pathogens isolated from the ECMO patients with post-operative nosocomial infections,and the drug resistance rates are high.The high blood glucose level,long duration of ECMO supporting treatment and long time of central venous catheter indwelling are the independent risk factors for the nosocomial infections in the patients treated with ECMO.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.

OBJECTIVE To explore the current status,etiological characteristics and risk factors for nosocomial in-fections in the patients who are treated with extracorporeal membrane oxygenation(ECMO)so as to provide bases for treatment and prevention of nosocomial infections in the ICU patients treated with ECMO.METHODS The clinical data were retrospectively collected from the patients who were treated with ECMO in the ICU of Xinyang Central Hospital from Jan.2021 to Dec.2023.The patients were divided into the infection group and the non-infec-tion group according the status of nosocomial infection during the ECMO treatment period.The constituent ratios of pathogens isolated from the patients with infections were recorded,and multivariate logistic regression analysis was performed for independent risk factors for the ECMO-related nosocomial infections.RESULTS Of 86 patients who were finally enrolled in the study,33(38.37％)had nosocomial infections.Totally 54 strains of pathogens were isolated from the patients with the infections,43(79.63％)of which were gram-negative bacteria,7(12.97％)were gram-positive bacteria,and 4(7.41％)were fungi.There were 36(66.67％)strains of multi-drug-resistant organisms(MDROs)among the 54 strains of pathogens,and 27(81.82％)patients were detected with MDROs.Among the ECMO patients with postoperative nosocomial infections,21(63.64％)cases had pul-monary infections,8(24.24％)cases had bloodstream infection,and 4(12.12％)had urinary system infections.Multivariate logistic analysis showed that the high blood glucose level at the beginning of treatment with ECMO,long duration of ECMO treatment and long time of central venous catheter indwelling were the independent risk factors for the nosocomial infections in the patients treated with ECMO(P＜0.05).CONCLUSION The isolation rate of gram-negative bacteria is relatively high among the pathogens isolated from the ECMO patients with post-operative nosocomial infections,and the drug resistance rates are high.The high blood glucose level,long duration of ECMO supporting treatment and long time of central venous catheter indwelling are the independent risk factors for the nosocomial infections in the patients treated with ECMO.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.