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 survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective To explore the effect of remote ischemic preconditioning (RIPC) on preoperative heart rate variability in patients with heart valves. Methods Patients scheduled to undergo on-pump cardiac valve surgery in the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, between January and July 2022 were initially enrolled. Eligible patients were randomly assigned at a 1 : 1 ratio to either the RIPC group or the control group. Relevant indicators of heart rate variability [standard deviation of NN interval (SDNN), standard deviation of mean value of NN interval in every five minutes (SDANN), mean square root of difference between consecutive NN intervals (RMSSD), percentage of adjacent RR interval>50 ms (PNN50), low frequency (LF) component, high frequency (HF) component and LF/HF] at 8 hours in the morning on the surgical day between two groups were compared. Results A total of 118 patients were initially assessed. After screening, 58 patients were excluded, and 60 patients provided written informed consent and were enrolled in the trial, with 30 allocated to the RIPC group and 30 to the control group. Seven patients in the control group and 5 patients in the RIPC group were subsequently excluded due to missing heart rate variability data resulting from cancelled operations. Finally, 23 patients in the control group and 25 patients in the RIPC group were included in the analysis. There was no statistical difference in baseline characteristics between the two groups, and there was no significant difference in heart rate variability 24 hours before intervention (P>0.05). After the intervention measures were taken, the comparison of the results of heart rate variability at 8 hours on the day of operation showed that SDNN and SDANN of patients in the RIPC group were higher than those in the control group, with statistical differences (P<0.05). Conclusion RIPC can stabilize the preoperative heart rate variability of patients undergoing cardiac valve surgery.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

The functional realization of proteins and other biological macromolecules depends on conformational dynamics and allosteric regulation, and elucidating their molecular mechanisms is an important foundation for understanding life processes. Molecular dynamics simulations are a powerful tool for investigating conformational evolution at the atomic level. However, traditional methods are limited by simulation timescales and high free-energy barriers, making it difficult to effectively capture rare conformations and their transition pathways. As a result, the development of enhanced sampling techniques has become key to overcoming this bottleneck. As a classical enhanced sampling technique, metadynamics suffers from several shortcomings, including strong dependence on collective variables and significant errors caused by bias potential accumulation. This article reviews three major improvement strategies. The first combines stochastic resetting with metadynamics, using trajectory-resetting mechanisms to improve sampling efficiency while avoiding the difficulty of optimizing collective variables. The second, SinkMeta, employs a “sinking” bias effect to enable efficient exploration of specific regions and paths. The third, OPES-based hybrid methods, improve the stability of free-energy estimation by optimizing the target distribution or the way the bias is constructed. These methods provide new ideas for characterizing free-energy landscapes and studying conformational transitions in complex biological systems, while also promoting the continued development of enhanced sampling methodologies.

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Objective:To compare the clinical outcomes of immediate breast reconstruction using latissimus dorsi flap with implant versus mesh with implant based on BREAST-Q evaluation.Methods:From the clinical database of the First Affiliated Hospital of Nanjing Medical University, the patients who underwent immediate breast reconstruction after total mastectomy from January 2020 to December 2023 were selected as the research subjects. All breast reconstruction surgeries were performed by the same surgeon. Patients were divided into two groups according to surgical methods: the latissimus dorsi muscle flap combined with implant immediate breast reconstruction group (LD group) and the mesh combined with implant immediate breast reconstruction group (mesh group). Patients were followed up in outpatient clinics or by telephone one year after surgery. The BREAST-Q was used to evaluate the surgical outcomes of both groups from four dimensions: psychosocial well-being, sexual well-being, chest-physical well-being, and breast satisfaction. The score range for each dimension was 0-100, with higher scores indicating greater patient satisfaction with quality of life and surgical outcomes. Statistical analysis was performed using SPSS 22.0 software. Normally distributed measurement data were expressed as Mean ± SD, and comparisons between the two groups were performed using independent sample t-test. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Results:A total of 123 patients were included, with 59 patients in the LD group and 64 patients in the mesh group. In the LD group, the mean age was (37.7±7.0) years, body mass index (BMI) was (22.6±2.6) kg/m 2, and clinical tumor staging showed 2, 22, 30, and 5 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. In the mesh group, the mean age was (39.1±7.0) years, BMI was (22.6±2.8) kg/m 2, and clinical tumor staging showed 1, 25, 38, and 0 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. There were no statistically significant differences between the two groups in baseline characteristics including age, BMI, and clinical tumor staging (all P>0.05). One year after surgery, the BREAST-Q result showed no statistically significant differences between the LD group and mesh group in psychosocial well-being [(83.0±19.8) points vs. (80.8±19.3) points] and sexual well-being [(62.1±30.4) points vs. (65.8±25.6) points] (all P>0.05). However, the LD group had lower chest-physical well-being scores than the mesh group [(40.6±9.7) points vs. (45.1±9.6) points, P<0.05], while breast satisfaction scores were higher in the LD group than in the mesh group [(68.0±17.8) points vs. (59.8±12.6) points, P<0.01]. Conclusion:Immediate breast reconstruction by both latissimus dorsi flap with implant and mesh with implant can improve patients’ psychosocial and sexual well-being by enhancing breast appearance. However, LD technique provides better breast satisfaction, while the mesh technique offers advantages in physical well-being of the chest wall and upper body. Surgeons should select the most appropriate breast reconstruction technique based on patients’ anatomical conditions, treatment history, and individual needs to optimize postoperative quality of life and satisfaction.

Objective:To investigate the efficacy and safety of percutaneous trans-hepatic choledochoscopic lithotripsy (PTCSL) in the treatment of recurrent hepatobiliary calculi under enhanced recovery after surgery (ERAS) mode.Methods:Clinical data of 88 patients with recurrent hepatobiliary calculi, who were treated with PTCSL at Zhengzhou Central Hospital Affiliated to Zhengzhou University and the First Affiliated Hospital of Xi'an Jiaotong University between June 2022 and June 2024 were retrospectively analyzed, including 34 males and 54 females, aged (52.0±13.8) years. The scheme includes preoperative education, prophylactic antibiotic application, ensuring the quality of surgery, early postoperative feeding and activity, etc. The operation can be divided into two fashions: percutaneous transhepatic cholangial drainage and PTCSL, which can be completed in one stage (one-stage expansion method) or in two stages (staged expansion method). Clinical data such as gender, age, operative time, intraoperative blood loss, residual stone, and surgical complications were recorded.Results:All 88 patients underwent PTCSL under ERAS mode successfully, including 52 cases using one-stage expansion method and 36 cases using staged expansion method. The operative time was (53±20) min, the intraoperative blood loss was (9.7±3.8) ml, the postoperative hospital stay was (3.6±1.7) d, and the hospitalization cost was (17 500±4 700) yuan. Sixty-nine patients (78.4%, 69/88) had one-time stone removal in the first PTCSL. A total of 19 cases of residual stones were managed again by percutaneous sinus soft choledochoscopy, of which 12 cases were managed by one-time choledochoscopy, five cases by two-time choledochoscopy, and two cases by three-time choledochoscopy. The rate of residual stone was significantly higher in one-stage expansion method compared to staged expansion method [28.8% (15/52) vs. 11.1% (4/36), P=0.040]. No death, conversion to open surgery, or severe complications such as intra-abdominal hemorrhage or bile leakage occurred in the patients. No residual stones or recurrence were found during the follow-ups of (7.5±2.1) months after discharge. Conclusion:PTCSL under ERAS mode is safe and effective in the treatment of recurrent hepatobiliary calculi.

Objective:To construct and evaluate the nomogram prediction model of spontaneous rupture of primary liver cancer (STRPLC), and make the web-based dynamic online nomogram.Methods:Clinical data of 346 patients with PLC treated in the Second Affiliated Hospital of Kunming Medical University were retrospectively analyzed, including 87 males and 15 females, aged 58.15±10.32 years. Single factor and multiple factor logistic regression analysis were used to screen the influencing factors of STRPLC, and the prediction model was constructed based on the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision analysis were used to evaluate the model. The web-based dynamic online nomogram was developed using the DynNom package in R4.3.1 software.Results:Multivariate logistic regression analysis showed that the independent risk factors for spontaneous rupture and hemorrhage of tumor were no history of systematic anti-tumor therapy, alpha-fetoprotein (AFP) level, tumor protrusion on liver surface, tumor length, invasion of major blood vessels, and moderate to large amount of ascites (all P<0.05). The area under the receiver operating characteristic curve (AUC) of the prediction model constructed by this nomogram is 0.913 (95% CI: 0.884-0.943), the best cutoff value is 0.254, with a sensitivity of 0.892, and a specificity of 0.803. The calibration curve shows a good agreement between the predicted probability and the actual probability. The decision curve of the model is above the two invalid lines of " none" and " all" in the horizontal range of 0.07-0.98, and the clinical net benefit of the model is >0. Then user-friendly web-based dynamic online nomogram is constructed. Conclusion:Large tumor size, superficial location, no history of systematic anti-tumor therapy, high AFP level, invasion of major blood vessels, and moderate to large amount of ascites are independent risk factors for STRPLC. The prediction model and dynamic online nanogram constructed by this method can effectively assess the risk of STRPLC.

OBJECTIVE To observe the changes of serum proteins in the mice with carbapenem-resistant hyperviru-lent Klebsiella pneumoniae(CR-hvKP)bloodstream infection by using liquid chromatogram-mass spectrometer(LC-MS),find out the differentially expressed proteins and carry out corresponding biological function analysis.METHODS The models of ICR mice with CR-hvKP and classical Klebsiella pneumoniae(cKP)bloodstream infec-tions were established,the serum specimens were collected from the mice at 12 hours of establishment of the in-fection models and were detected by using LC-MS.The result of LC-MS was identified by using Maxquant soft-ware.The corresponding bioinformatics analysis was performed for the differentially expressed proteins.RESULTS As compared with the normal control group,there were 24 upregulated proteins and 20 downregulated proteins in CR-hvKP group.As compared with cKP group,there were 107 upregulated proteins in the CR-hvKP group.The 134 differentially expressed proteins were retrieved one by one from Uniprot database,it was found that the pro-teins were involved in biological regulation,immune process,biological interaction,movement,metabolic process,response to stimulation,signal transduction,inflammatory response,oxidative stress and angiogenesis.The signal pathway analysis involved multiple metabolism-related pathways,including complement and coagula-tion cascades,cholesterol metabolism,bacterial infection,heme clearance,and assembly,remodeling and clear-ance of plasma lipoprotein.In terms of the proteins being attached great importance,the expression levels of kal-likrein B1(KLKB1)and serpin family A(Serpina)1b were downregulated as compared with the normal control group and were upregulated as compared with the cKP group;the expression levels of serum amyloid A protein(SAA)1,SAA2,Vanin-3(VNN3)and hemoglobinβpolypeptide chain b2(HBB-b2)were upregulated as com-pared with both the cKP group and the normal control group.CONCLUSIONS The CR-hvKP bloodstream infection involves the activation and action of multiple proteins.The rise of SAA1,SAA2,VNN3 and HBB-b2 or the de-cline of KLKB1 and Serpina1b may indicate the CR-hvKP bloodstream infection.