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 analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.

Objective:To analyze the relationship between microRNA-21(miR-21)expression and the risk of very early relapse post-induction chemotherapy in children with acute lymphoblastic leukemia(ALL).Methods:A total of 110 newly diagnosed children with ALL admitted to Huanggang Central Hospital from March 2020 to September 2022 were included.All patients received induction chemotherapy according to the CCLG-2008 protocol.The patients who achieved complete response(CR)after induction chemotherapy were followed up for 18 months,with very early relapse as the endpoint event.Then the patients were divided into a relapse group and a non-relapse group.Cox regression was used to analyze the influencing factors of very early relapse after induction chemotherapy in children with ALL.ROC curve and decision curve were used to evaluate the predictive value of peripheral blood miR-21 for very early relapse after induction chemotherapy in children with ALL.Restricted cubic splines were used to analyze the dose-response relationship between peripheral blood miR-21 and very early relapse after induction chemotherapy in children with ALL.Results:A total of 102 children with ALL achieved CR after induction chemotherapy,among whom 24 cases(23.53％)experienced very early relapse,with a median relapse time of 14 months.The proportions of patients with high-risk stratification at initial diagnosis,extramedullary infiltration,and minimal residual disease(MRD)positivity were significantly higher in the relapse group than those in the non-relapse group;The absolute lymphocyte count(ALC)in peripheral blood was significantly lower,while the expression levels of miR-21 and lactate dehydrogenase(LDH)were significantly higher in the relapse group compared with the non-relapse group(all P＜0.05).Cox regression analysis showed that very early relapse after induction chemotherapy in children with ALL was associated with medium risk and high risk at initial diagnosis,extramedullary infiltration,decreased ALC in peripheral blood,MRD positivity,as well as high expression levels of miR-21 and LDH(all P＜0.05).ROC curve analysis indicated that the area under the curve(AUC)of peripheral blood miR-21 for predicting very early relapse after induction chemotherapy in children with ALL was 0.800,with an optimal cutoff value of 4.830.Restricted cubic spline analysis revealed that there was a non-linear dose-response relationship between peripheral blood miR-21 and the risk of very early relapse after induction chemotherapy in children with ALL.When the expression level of peripheral blood miR-21 exceeded 4.830,the risk of very early relapse increased with the elevation of miR-21 expression.Decision curve analysis demonstrated that combining peripheral blood miR-21 with other risk factors enhanced the predictive performance for the risk of very early relapse after induction chemotherapy in children with ALL.Conclusion:Very early relapse after induction chemotherapy in children with ALL is associated with elevated expression of miR-21 in peripheral blood,and high expression of miR-21 may increase the risk of very early relapse.Detecting miR-21 before induction chemotherapy has predictive significance for very early relapse in children with ALL,and combining it with other risk factors can improve the predictive efficacy.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Innovative drugs are defined as new chemical entities that play a vital role in the treatment and maintenance of human health. While single-target innovative drugs have achieved notable success, they face limitations in addressing the increasingly complex and precise spectra of diseases. The advent of multi-target innovative drugs offers new opportunities, supported by a growing body of pharmacological evidence. Herbal medicines are recognized as valuable sources of multi-target therapeutics due to their proven efficacy in treating complex diseases. However, the identification and validation of such drugs from herbal sources continue to pose significant challenges. This paper presents a comprehensive review of the literature on traditional Chinese medicine, integrated medicine, chemistry, and biology from 2015 to 2025. It summarizes the strategies employed in integrating traditional Chinese and Western medicine for innovative drug development, along with successful application cases. We believe these efforts will deepen understanding of the current landscape, accelerate the discovery of multi-target innovative drugs from herbal medicine, and contribute to addressing major human health challenges.

OBJECTIVE To analyze the prevalence of hospital-associated carbapenem-resistant Enterobacter(CRE)infections among the elderly intensive care unit(ICU)patients with respiratory system diseases based on the Chinese healthcare security diagnosis-related groups(CHS-DRG)and the case mix index(CMI)and assess the economic burden and consumption of healthcare insurance funds.METHODS The key departments with high isola-tion rate of CRE and high incidence of hospital-associated infections were found out by using CMI.The data were collected from 56 elderly patients with major diagnostic category E(MDCE)who had hospital-associated Enter-obacter infection and were treated in 10 ICUs of the Second People's Hospital of Changzhou from 2021 to 2023.The length of hospital stay,economic burden and consumption of healthcare insurance funds were observed and compared between the CRE infection group and the carbapenem-sensitive Enterobacter(CSE)infection group.RESULTS The general ICU(Yanghu campus)ranked the top 3 isolation rate of CRE and incidence of hospital-associated in-fections after the adjustment of CMI value.EJ1(other respiratory system surgeries)and ES2(respiratory sys-tem infection/inflammation)were the core codes of major Enterobacter infection.The average length of hospital stay of the CRE group was 10 days larger than the CSE group,the self-funded amount was 20,777.65 yuan more in the CRE group than in the CSE group;the consumption of healthcare insurance funds was 39,631.64 yuan more in the CRE group than in the CSE group(P＜0.05).Of the patients encoded with ES2,the average length of hospital stay was 6.5 days more in the CRE group than in the CSE group,and the fund expense on pay-ment of severe diseases was greater in the CRE group than in the CSE group(P＜0.05).CONCLUSIONS The CRE infection may increase the length of hospital stay,economic burden and consumption of healthcare insurance funds of the elderly ICU patients with respiratory system diseases.Under the CHS-DRG payment mode,it is nec-essary to take targeted prevention and control strategies according to the characteristics of patients with different DRG codes so as to control the wide spread of CRE.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

Objective:To explore the development process of family resilience in children with congenital pseudarthrosis of the tibia (CPT) and to understand the long-term challenges and coping strategies that CPT imposes on the families of affected children.Methods:This study combined purposive sampling and theoretical sampling. It selected 15 caregivers of CPT children from Hunan Children's Hospital for semi-structured interviews. Grounded theory was used to analyze the interview results.Results:The development of family resilience in CPT children's families occurred in three stages: pre-formation stage, formation stage, and maintenance stage. In facing negative emotions and family challenges, caregivers first needed to rebuild their inner beliefs. They then adjusted the family organizational model, adopted open and inclusive communication, and actively sought external support to foster the development of family resilience. Ultimately, caregivers were able to self-regulate their emotions, accumulate caregiving experience, and begin to shift their life perspective.Conclusions:The development of family resilience in CPT children's families is a dynamic, multi-stage process with interactions of multiple factors. Healthcare providers should offer professional health guidance according to the different stages of family development. Moreover, the government and schools should increase their attention and support, working together with families and healthcare providers to enhance family resilience for children with CPT.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.