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.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective To explore the efficacy of magnetic resonance angiography(MRA)combined with CXC motif chemokine ligand 12(CXCL12)in predicting ischemic stroke in patients with transient ischemic attack(TIA).Methods A total of 225 patients with TIA were selected,and all patients underwent MRA and CXCL12 examination before treatment.The occurrence of ischemic stroke in TIA patients was counted within 1 week of treatment,the factors influencing the occurrence of ischemic stroke in TIA patients were analyzed,and the value of MRA combined with CXCL12 in predicting the occurrence of ischemic stroke in TIA patients was ana-lyzed.Results Among the 225 patients,21 of them had ischemic stroke.Multivariate logistic regression analysis showed that Essen stroke risk scale(ESRS)score,lesion site stenosis,and CXCL12 level were the factors influencing the occurrence of ischemic stroke in TIA patients(P<0.05).The receiver operating characteristic(ROC)curve showed that the sensitivity of lesion site stenosis,CXCL12 and their combination in predicting the occurrence of ischemic stroke in TIA patients was 76.19%,71.43%,and 85.71%,respectively,the specificity was 80.39%,70.10%,and 88.73%,respectively,and the area under the curve(AUC)was 0.798,0.733,and 0.895,respectively.Conclusion MRA combined with CXCL12 has good efficacy in predicting the occurrence of ischemic stroke in TIA patients.

Objective To systematically review and analyze the characteristics and current status of registered clinical trials on Traditional Chinese Medicine(TCM)for the prevention and treatment of overweight/obesity.Methods We conducted a comprehensive search of two primary clinical trial registration platforms,the Chinese Clinical Trial Registry and ClinicalTrials.gov,to extract registered information on TCM interventions for overweight/obesity.The search period spanned from the establishment of each registry to December 31,2024.Statistical analysis was performed on the extracted registration data.Results A total of 226 clinical studies were included,with a cumulative sample size of 25165 participants.The annual registration volume exhibited a significant upward trend.The majority of studies were interventional in design,with primary outcome measures focusing on anthropometric and metabolic indicators.Notably,only two trials fully met the international standards for clinical trial registration as outlined by the World Health Organization(WHO).Conclusion A quality assessment of the overall registration data revealed that the quality of trial registrations remains suboptimal.Issues such as inadequate standardization,transparency,and comprehensiveness were identified.Additionally,the geographical distribution of registered trials was uneven,and there is an urgent need to refine outcome measures related to TCM syndrome differentiation.

With the development of society,the incidence of obesity has increased year by year in recent years,which has seriously jeopardized public health and safety,and has been a hot spot in the field of endocrine research.At the same time,obesity is also an important cause of a variety of metabolic diseases,such as metabolic syndrome,pre-diabetes,hypertension and polycystic ovary syndrome and other diseases,but the etiology and mechanism of obesity have not been completely clear,and basic research on obesity of traditional Chinese and western medicine still needs to be widely carried out.In this paper,animal models of obesity and its complications will be comprehensively summarized,and the model principles will be elaborated in combination with TCM syndromes and western medicine mechanisms,and evaluate their merits and demerits,so as to provide references for the selection of reasonable animal models for relevant experimental studies of obesity.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.

Objective To systematically review and analyze the characteristics and current status of registered clinical trials on Traditional Chinese Medicine(TCM)for the prevention and treatment of overweight/obesity.Methods We conducted a comprehensive search of two primary clinical trial registration platforms,the Chinese Clinical Trial Registry and ClinicalTrials.gov,to extract registered information on TCM interventions for overweight/obesity.The search period spanned from the establishment of each registry to December 31,2024.Statistical analysis was performed on the extracted registration data.Results A total of 226 clinical studies were included,with a cumulative sample size of 25165 participants.The annual registration volume exhibited a significant upward trend.The majority of studies were interventional in design,with primary outcome measures focusing on anthropometric and metabolic indicators.Notably,only two trials fully met the international standards for clinical trial registration as outlined by the World Health Organization(WHO).Conclusion A quality assessment of the overall registration data revealed that the quality of trial registrations remains suboptimal.Issues such as inadequate standardization,transparency,and comprehensiveness were identified.Additionally,the geographical distribution of registered trials was uneven,and there is an urgent need to refine outcome measures related to TCM syndrome differentiation.

This paper reviews the current application status of big language model in nursing, the needs for information technology development in critical care nursing, the current application status of and future development direction of big language model in critical care nursing, as well as the risks and challenges faced, with a view to providing a reference for promoting the application of big language model in critical care nursing.

P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.