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 evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions， as well as to review the payment methods of drugs （including in-hospital and external drug dispensing）. METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally， an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 （before the system upgrade） and May to August 2025 （after the system upgrade）. RESULTS After the upgrade of the pre-prescription review system， the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval （CI）＝0.3%-6.7%， P ＝0.037 ] ； the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level （95%CI＝31.6%-88.5%， P ＝0.026）， and the average monthly sequential decrease was 29.5% （95%CI＝12.2%-43.4%， P ＝0.012）. Moreover， the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade， a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs， and strengthens the supervision of off-label drug use， achieving dual guarantees of clinical rationality and medical insurance compliance.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Background As common public facilities essential to daily life, hair and beauty salons frequently contain various airborne toxic and hazardous pollutants potentially leading to adverse health effects for salon practitioners. Objective To characterize the indoor air pollution profiles of common contaminants in hair and beauty salons in Shanghai and to evaluate the associated health risks for practitioners, in order to provide a scientific basis for strengthening the public health management in Shanghai and protecting the health of practitioners. Methods The air quality monitoring data of hair and beauty salons in Shanghai from 2016 to 2024 were obtained from the “Health Hazard Factors Monitoring Program for Public Places” of the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention. Monitoring indicators included particulate matter ≤10 μm in aerodynamic diameter (PM₁₀), particulate matter ≤2.5 μm in aerodynamic diameter (PM_2.5), formaldehyde, ammonia, benzene, toluene, and xylene. Indicator compliance rates were calculated across various years in accordance with GB 9666-1996 Hygienic standard for barber shop and beauty shop and GB 37488-2019 Hygiene indicators and limit for public places; specifically, PM_2.5 was assessed against the limits stipulated in GB/T 18883-2022 Standards for indoor air quality. A questionnaire survey was conducted among salon practitioners to collect weekly working days and daily working hours. The non-carcinogenic risks associated with inhalation exposure to formaldehyde, ammonia, benzene, toluene, and xylene as well as the carcinogenic risks posed by formaldehyde and benzene were evaluated following WS/T 777-2021 Technical guide for environmental health risk assessment of chemical exposure and the U.S. Environmental Protection Agency inhalation risk model. Results The overall compliance rates of PM₁₀, formaldehyde, ammonia, benzene, and toluene in the air of hair and beauty salons in Shanghai from 2016 to 2024 were 92.13%, 96.59%, 96.15%, 94.93%, and 94.97%, respectively; the overall compliance rate of xylene was a little lower (85.92%), and the overall compliance rate of PM_2.5 was 57.18%. The P₅₀ concentrations of PM₁₀, PM_2.5, formaldehyde, ammonia, benzene, toluene, and xylene did not exceed the corresponding limits. The P₅₀ of non-carcinogenic risk indicator (hazard quotient, HQ) for formaldehyde, ammonia, benzene, toluene, and xylene were <1. The probabilities of non-carcinogenic risk HQ >1 for formaldehyde and xylene were 41.4% and 10.9%, respectively, which were higher than that of other pollutants. The P₅₀ of carcinogenic risk (CR) for formaldehyde and benzene were between 1.0×10⁻⁶ and 1.0×10⁻⁴, while the probabilities of CR >1.0×10⁻⁴ were 16.9% and 14.0%, respectively. Conclusion The overall compliance rate of common pollutant concentrations in the air of hair and beauty salons in Shanghai is high, and the hygienic condition meets the requirements of national standards. The non-carcinogenic health risks posed by formaldehyde and xylene to employees (with formaldehyde being more prominent), as well as the carcinogenic risks associated with formaldehyde and benzene, deserve heightened attention in future health supervision.

Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

Objective To clarify the risk factors of diaphragmatic dysfunction (DD) after cardiac surgery with extracorporeal circulation. Methods A retrospective analysis was conducted on the data of patients who underwent cardiac surgery with extracorporeal circulation in the Department of Cardiovascular Surgery of Peking University People's Hospital from January 2023 to March 2024. Patients were divided into two groups according to the results of bedside diaphragm ultrasound: a DD group and a control group. The preoperative, intraoperative, and postoperative indicators of the patients were compared and analyzed, and independent risk factors for DD were screened using multivariate logistic regression analysis. Results A total of 281 patients were included, with 32 patients in the DD group, including 23 males and 9 females, with an average age of (64.0±13.5) years. There were 249 patients in the control group, including 189 males and 60 females, with an average age of (58.0±11.2) years. The body mass index of the DD group was lower than that of the control group [(18.4±1.5) kg/m2 vs. (21.9±1.8) kg/m2, P=0.004], and the prevalence of hypertension, chronic obstructive pulmonary disease, heart failure, and renal insufficiency was higher in the DD group (P<0.05). There was no statistical difference in intraoperative indicators (operation method, extracorporeal circulation time, aortic clamping time, and intraoperative nasopharyngeal temperature) between the two groups (P>0.05). In terms of postoperative aspects, the peak postoperative blood glucose in the DD group was significantly higher than that in the control group (P=0.001), and the proportion of patients requiring continuous renal replacement therapy was significantly higher than that in the control group (P=0.001). The postoperative reintubation rate, tracheotomy rate, mechanical ventilation time, and intensive care unit stay time in the DD group were higher or longer than those in the control group (P<0.05). Multivariate logistic regression analysis showed that low body mass index [OR=0.72, 95%CI (0.41, 0.88), P=0.011], preoperative dialysis [OR=2.51, 95%CI (1.89, 4.14), P=0.027], low left ventricular ejection fraction [OR=0.88, 95%CI (0.71, 0.93), P=0.046], and postoperative hyperglycemia [OR=3.27, 95%CI (2.58, 5.32), P=0.009] were independent risk factors for DD. Conclusion The incidence of DD is relatively high after cardiac surgery, and low body mass index, preoperative renal insufficiency requiring dialysis, low left ventricular ejection fraction, and postoperative hyperglycemia are risk factors for DD.

ObjectiveTo investigate the molecular mechanisms of Mahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， in repairing podocyte injury based on the sweat pore theory， with a focus on the podocyte cytoskeletal transient receptor potential canonical 5 （TRPC5）-Ras-related C3 botulinum toxin substrate 1 （RAC1） feedforward loop. MethodsAn animal model with puromycin aminonucleoside （PAN）-induced overexpression of TRPC5 was established. Interventions included Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone. Biochemical parameters ， histopathological changes， and podocyte ultrastructure were analyzed. Western blotting was performed to determine the expression of cytoskeletal protein synaptopodin and mechanism-related proteins TRPC5， RAC1-GTP， and RAC1 in the kidney. Primary podocytes were isolated and cultured for three-dimensional imaging of foot processes， cytoskeletal fluorescence analysis， and TRPC5-RAC1 co-staining via immunofluorescence. ResultsCompared with the model group， Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone increased serum albumin （ALB）， decreased UPCR， reduced podocyte foot process fusion rate， upregulated synaptopodin expression， and downregulated TRPC5， RAC1-GTP， and RAC1 expression （P<0.05）. Moreover， the interventions increased the phalloidin fluorescence area/field area ratio （P<0.01） and mean fluorescence intensity （P<0.05）， while decreasing the proportion of TRPC5-RAC1 co-stained double-positive cells/total cells per field （P<0.01） in primary podocytes. ConclusionMahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， ameliorated podocyte injury in the model with PAN-induced TRPC5 overexpression by reducing proteinuria and suppressing the TRPC5-RAC1 feedforward loop-mediated podocyte cytoskeletal damage.