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 expression levels of T cell receptor(TCR)ζchain and Zeta-chain-associated protein kinase 70(ZAP70)in peripheral blood of patients with primary Sj?gren syndrome(PSS).Methods Thirty-six patients with PSS who were treated at Jiujiang NO.1 People's Hospital from January to June 2024 were enrolled in observation group,and 30 healthy subjects during the same period were enrolled in control group.Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of TCRζ chain and ZAP70 in peripheral blood mononuclear cells,and flow cytometry was used to detect peripheral blood T cell subsets.Pearson correlation was used to analyze the correlation between TCRζ chain,ZAP70 and other detection indicators.Results The relative expression levels of TCRζ chain and ZAP70 in observation group were significantly lower than those in control group(P＜0.05),while CD8+and interleukin-6(IL-6)were significantly higher than those in control group(P＜0.05).Pearson correlation analysis showed that TCRζ chain was positively correlated with CD4+,and negatively correlated with CD8+and IL-6(P＜0.05).ZAP70 was negatively correlated with CD8+and IL-6(P＜0.05).Conclusion The expressions of TCRζ chain and ZAP70 are down-regulated in PSS patients,which may exacerbate the immune disorder of PSS through abnormal T cell signal transduction.

Objective:To systematically evaluate the efficacy and safety of intravenous thrombolysis with tenecteplase (TNK) in acute ischemic stroke (AIS) across different time windows.Methods:Randomized controlled trials investigating TNK in AIS were retrieved from PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wanfang databases, with data collected up to May 2025. Experimental group received intravenous thrombolysis with 0.25 mg/kg TNK, either alone or in combination with mechanical thrombectomy (MT). Control group received alteplase, placebo, standard medication (containing butylphthalide), MT, or above-mentioned drugs combined with MT. These patients were within 4.5 hours of onset (within-time window) or within 4.5-24 hours of onset (extended-time window). Efficacy indexes included functional outcome excellent rate (modified Rankin scale [mRS] score of 0-1 at 3 months after treatment), early neurological improvement rate (National Institutes of Health Stroke Scale [NIHSS] score improvement≥4 or NIHSS score ranged 0-1 within 72 of treatment), and recanalization rate 24 h after treatment. Safety indexes comprised symptomatic intracranial hemorrhage (sICH) rate within 48 h of treatment, and mortality rate and rate of serious adverse events (SAEs) within 90 d of treatment. Quality of the trials was assessed according to Cochrane handbook for systematic reviews of interventions (version 5.1). Meta-analysis was conducted using Stata software, with pooling data as risk difference ( RD). Results:Sixteen articles (11 were within-time window ones, and 5 were extended-time window ones), involving 9,430 AIS patients, were included. Quality grade of these articles is B-level. (1) In articles of within-time window: the experimental group had a significantly higher functional outcome excellent rate compared with the control group ( RD=0.031, 95% CI: 0.009-0.052, P=0.005); no significant difference was observed in early neurological improvement rate ( RD=0.016, 95% CI: -0.012-0.043, P=0.260), recanalization rate ( RD=0.040, 95% CI: 0.000-0.081, P=0.053), sICH rate ( RD=0.005, 95% CI: -0.002-0.012, P=0.198), mortality rate ( RD=0.000, 95% CI: -0.012-0.013, P=0.950), or SAE rate ( RD=0.003, 95% CI: -0.028-0.033, P=0.870) between the two groups. (2) In articles of extended-time window: the experimental group exhibited significantly higher functional outcome excellent rate ( RD=0.064, 95% CI: 0.016-0.113, P=0.009), early neurological improvement rate ( RD=0.101, 95% CI: 0.023-0.180, P=0.012), and recanalization rate ( RD=0.131, 95% CI: 0.059-0.203, P<0.001) compared with the control group; no significant difference was found in sICH rate ( RD=0.014, 95% CI: -0.003-0.032, P=0.097), mortality rate ( RD=0.006, 95% CI: -0.030-0.041, P=0.752), or SAE rate ( RD=0.030, 95% CI: -0.037-0.097, P=0.385) between the two groups. Conclusion:Intravenous thrombolysis with TNK is safe and effective in AIS patients at both within-time window and extended-time window.

Objective:To summarize and analyze the clinical characteristics of systemic lupus erythematosus (SLE) combined with ischaemic stroke and the factors associated with poor prognosis.Methods:A total of 50 patients with SLE combined with ischaemic stroke in the First Affiliated Hospital of Xi′an Jiaotong University from January 2014 to June 2024 were included in the study, the clinical data of the patients were retrospectively collected and summarized, the Shapiro-Wilk test was used to assess the normality of data, and the factors related to poor prognosis were analyzed by logistic regression analyses.Results:Fifty patients with SLE combined with ischaemic stroke had a mean age of (47.1±15.5)years, 80.0%(40/50) were female, the duration of SLE was (5.6±6.3)years, the mean SLEDAI-2K score was (14.3±4.1), the rate of anticardiolipin antibody positivity was 30.0%(15/50), and the rate of β 2-glycoprotein Ⅰ antibody positivity was 28.0%(14/50). The most common clinical manifestations of stroke were impaired limb movement (34.0%) (17/50), cerebral infarction mainly in the cerebral hemisphere (82.0%)(41/50), combined with cerebral haemorrhage in 6.0%(3/50), cerebral leukoencephalopathy in 26.0%(13/50), and cerebral atrophy in 24.0%(12/50). In terms of treatment, the most used immunosuppressant was cyclophosphamide (34.0%, 17/50), 64.0%(32/50) of patients received aspirin, 32.0%(16/50) received clopidogrel and 14.0%(7/50) received anticoagulation. Four deaths and 12 cases of severe disability were found in 50 patients at follow-up, and SLEDAI-2000 scores were positively correlated with the above poor prognosis using univariate [ OR(95% CI)=1.407(1.123,1.764), P=0.003] and multivariate [ OR(95% CI)=1.388(1.097, 1.756), P=0.006] regression analyses. Conclusion:Patients with SLE combined with ischaemic stroke had high disease activity in SLE, and SLEDAI-2000 scores were positively associated with poor prognosis of death and severe disability.

Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.

Objective To investigate the expression levels of T cell receptor(TCR)ζchain and Zeta-chain-associated protein kinase 70(ZAP70)in peripheral blood of patients with primary Sj?gren syndrome(PSS).Methods Thirty-six patients with PSS who were treated at Jiujiang NO.1 People's Hospital from January to June 2024 were enrolled in observation group,and 30 healthy subjects during the same period were enrolled in control group.Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of TCRζ chain and ZAP70 in peripheral blood mononuclear cells,and flow cytometry was used to detect peripheral blood T cell subsets.Pearson correlation was used to analyze the correlation between TCRζ chain,ZAP70 and other detection indicators.Results The relative expression levels of TCRζ chain and ZAP70 in observation group were significantly lower than those in control group(P＜0.05),while CD8+and interleukin-6(IL-6)were significantly higher than those in control group(P＜0.05).Pearson correlation analysis showed that TCRζ chain was positively correlated with CD4+,and negatively correlated with CD8+and IL-6(P＜0.05).ZAP70 was negatively correlated with CD8+and IL-6(P＜0.05).Conclusion The expressions of TCRζ chain and ZAP70 are down-regulated in PSS patients,which may exacerbate the immune disorder of PSS through abnormal T cell signal transduction.

AIM:To investigate the types and mechanisms of lung injury induced by high-altitude exposure in mice.METHODS:Eight-week-old male C57BL/6 mice were randomly assigned to a normoxia group and a hypobaric hy-poxia exposure group,with 10 mice in each group.The hypobaric hypoxia group was continuously exposed to a hypobaric hypoxia environment simulating an altitude of 6 000 m for 3 d to establish an acute lung injury model.Lung tissues were collected.Lung pathological changes were evaluated using HE and Masson staining.Transcriptome analysis was conducted using DESeq2 and ClusterProfiler to identify differentially expressed genes and pathways,and hub genes were screened us-ing the STRING database.RESULTS:Compared with the normoxia group,the hypobaric hypoxia group exhibited signifi-cant increases in alveolar septal thickness,hyaline membrane formation,and neutrophil infiltration both in the alveolar space and the interstitial space,along with elevated lung injury scores(P<0.01),with no significant fibrosis observed.The mRNA levels of Alas2,Slc4a1,Rhag,Car1,Car2,Hbb,Agtr1b,Bmp2,Bmper,Vegfc,Foxm1,Fgf18,Igf1,Cx-cl12 and Mmp14 genes were significantly elevated(P<0.01),while Notch1,Notch4 and Cxcr4 mRNA levels were signifi-cantly decreased(P<0.01).Protein levels of inducible nitric oxide synthase(iNOS),cleaved caspase-3,cleaved PARP,fibronectin,elastin,tenascin C,tissue inhibitor of metalloproteinase-1(TIMP1),WNT3a,and β-catenin were signifi-cantly increased(P<0.05).CONCLUSION:Short-term high-altitude hypobaric hypoxia exposure induced acute lung in-jury in mice by significantly altering the expression of genes involved in apoptosis,vascular permeability regulation,extra-cellular matrix remodeling,and type Ⅱ alveolar epithelial cell proliferation.

Objective To propose a Weka-based method for classifying acute lymphoblastic leukemia(ALL)images,aiming to improve ALL cell classification accuracy and stability.Methods Firstly,totally 180 images were randomly selected from ALL-IDB2 subset of Acute Lymphoblastic Leukemia Image Database(ALL-IDB),including 90 images of patients and 90 images of healthy people;secondly,the image preprocessing was carried out using ImageJ software and image features were extracted such as texture,edge and shape;thirdly,image classification was implemented with four classifiers of Weka,including random forest(RF),Bayesian network(BN),J48 decision tree and sequential minimal optimization(SMO),and the key parameters of each classifier were optimized;finally,the performance of the classifiers was verified using 80 independent test images.Results Before parameter optimization,the accuracy of RF,J48 decision tree,BN and SMO classifiers was 94.3％,86.2％,83.6％and 83.0％,respectively.After optimization,the accuracy increased to 95.2％,86.3％,86.3％and 89.7％,respectively.After optimization,RF behaved the best on the independent test set with a classification accuracy of 90.0％,followed by SMO(81.3％),BN(81.3％)and J48 decision tree(75.0％).Conclusion The Weka-based ALL image classification method with a high accuracy is efficient and reliable for automated classification of ALL cell.[Chinese Medical Equipment Journal,2025,46(2):10-15]

Objective:To explore the protective effect and mechanism of Rougan Tongluo Decoction on ischemic stroke induced motor disorder rats based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Cysteinyl aspartate specific proteinase 1(Caspase-1)pathway.Methods:Establishing a rat model of ischemic stroke with motor disorders using the modified suture method.The rats were randomly divided into model control group,Rougan Tongluo Decoction low,medium and high dose groups and butylphthalide soft capsule group,with 10 rats in each group,Another 10 rats were selected as sham surgery group.After 28 days of administration,the neurological function of rats in each group was evaluated by the Zea-Longa scoring method;The forelimb grasping force of rats in each group was detected by grip tester;The coordination ability of rats was evaluated by rat-mouse rotarod instrument;The expression of NLRP3,GSDMD,Caspase-1 protein and Interleukin-1β(IL-1β)was detected by immunohistochemistry.Results:The NLRP3,Caspase-1,GSDMD protein and IL-1β expression Zea-Longa score in the cerebral cortex of the model control group were significantly higher than those in sham surgery group,the forelimb grasping force was lower than that in sham surgery group,and the latency period for turning the baton was shorter than that in sham surgery group(P＜0.05).The Zeba-Longa score,NLRP3,Caspase-1,GSDMD protein and IL-1 β expression in the cerebral cortex the butylphthalide soft capsule group,low dose,medium dose,high dose Rougan Tongluo decoction group were lower than those in model control group,the forelimb grasping force was higher than that in model control group,and the latency period for turning the baton was longer than that in model control group(P＜0.05).Conclusion:Rougan Tongluo Decoction may alleviate inflammatory response by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to improve neurological function and motor ability in ischemic stroke induced motor disorder rats.

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.