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 pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1％DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P＜0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P＜0.05),while the viabilities of TM3 cells in other groups had no significant changes(P＞0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P＜0.05),the expression levels of PI3K protein were decreased(P＜0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P＜0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P＜0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P＜0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P＜0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P＜0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P＜0.05),and the expression levels of IFT80 mRNA(P＜0.01)and Bax protein(P＜0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P＜0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P＜0.05),while the expression level of RNF130 mRNA was increased(P＜0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P＜0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.

Childhood primary renal tubular diseases are chronic kidney diseases characterized by impaired renal tubular reabsorption. Primary renal tubular disease has diverse clinical manifestations and lacks of specificity. Laboratory tests are limited，making it prone to missed diagnosis and misdiagnosis. Based on the current knowledge of renal tubular diseases，authors propose early warning signals of renal tubular diseases such as family history of primary tubular diseases，unexplained polyhydramnios during pregnancy，polydipsia，polyuria，delayed growth and development or rickets，decreased muscle strength and tone，unexplained electrolyte disturbance，hyperuricemia，acid-base disturbance，positive urine sugar test，renal tubular proteinuria，urinary imaging examination suggesting kidney stones，calcium deposition，renal cysts and early onset of eye，ear，joint and neuron injury.Meanwhile，some universal management strategies for primary renal tubular disease are proposed，emphasizing the importance of multidisciplinary collaboration，genetic testing and individualized intervention to improve the long-term prognosis of childhood primary renal tubular diseases.

Objective To develop a multifunctional vision examination device for confined cabin environments to meet the requirements for detecting and collecting visual function parameters in military training and scientific research.Methods A multifunctional vision examination device was designed with a segmented mode and composed of an exmaination terminal and a control terminal.The examination terminal was composed of a sealed box,a high-definition display,an isolation baffle and a rubber eye mask.The sealed box had a fully closed structure,and the space design in the box was carried out in the form of integrating sphere;the high-definition display had a floating structure not rigidly connected with the surrounding components,and adopted a non-standard screen as the main display;the edges of the isolation baffle were sealed,and a spring washer for mechanical positioning was placed between the baffle and the sealed box.The control terminal software was programmed with C language,and there were several funcational modules involved in the software part for basic information management,function testing and summary report.Results Trials in the low-pressure chamber showed the device developed could be used for testing near vision,stereoscopic vision,contrast sensitivity,rapid dark adaptation and dark vision under the simulated altitude of 5 000 m when the examinee wore an oxygen mask,with remote operation enabled during the testing.Conclusion The multifunctional vision examination device gains advantages in light weight,high portability and compatibility with confined cabin environments,and meets the requirements for visual function testing in military training and scientific research.[Chinese Medical Equipment Journal,2025,46(5):21-26]

Objective:To explore the longitudinal predictive relationship between self-neglect and frailty among older adults.Methods:Data were drawn from the Chinese Longitudinal Healthy Longevity Survey conducted in 2011 (T1), 2014 (T2), and 2018 (T3). A total of 1 495 older adults aged≥65 years at T1 who participated in three consecutive surveys and had no missing key variables were included. General demographic information, self-neglect scores, and frailty status were extracted. Spearman correlation analysis was used to examine the association between self-neglect and frailty. Cross-lagged analysis was employed to investigate the potential causal relationship between the two variables.Results:The self-neglect scores for 1 495 older adults at T1, T2, and T3 were (2.84±1.39), (2.47±1.30), and (2.41±1.20), respectively, showing a declining trend. The frailty scores at T1, T2, and T3 were 0 (0, 1.00), 0 (0, 2.00), and 1.00 (0, 2.00), respectively, indicating an increasing trend. Cross-lagged analysis revealed that self-neglect at T1 positively predicted frailty at T2 (β=0.076, P=0.004). Frailty at both T1 and T2 positively predicted self-neglect at T2 (β=0.057, P=0.044) and T3 (β=0.058, P=0.029), respectively. Conclusions:Frailty among older adults positively predicts self-neglect, and self-neglect also has a certain predictive effect on frailty. Medical staff should strengthen early screening and intervention for frailty in older adults to delay the occurrence and progression of self-neglect.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Objective:To investigate the correlation between transabdominal bowel ultrasongraphy (TBUS) parameters and disease activity of ulcerative colitis (UC).Methods:The results of TBUS, endoscopy and laboratory tests of 68 UC patients (108 examinations) who visited the Department of Gastroenterology of the Second Hospital (Eastern Campus) of Hebei Medical University From January 2022 to February 2024 were retrospectively analyzed. According to Mayo endoscopic score (MES), there were 10 cases of remission (MES=0) and 98 cases of active phase (MES>0); patients in active phase further classified into 16 cases of mild (MES=1), 19 cases of moderate (MES=2), and 63 cases of severe (MES=3). The TAUS parameters were compared between patients in remission and active phases. Spearman rank correlation analysis was used to analyze the correlation between the TBUS parameters including bowel wall thickness (BWT), Limberg score, wall layer stratification, fat wrapping and endoscopic activity score, laboratory inflammatory indicators. Receiver operating characteristic curve (ROC) analysis was applied to evaluate the predictive efficacy of the TBUS parameters and laboratory inflammatory indicators in identifying remission under endoscopy. Independent sample t-test and Fisher′s exact probability method were used to compare the two groups. Results:The BWT of patients in remission was significantly thinner than that of patients in active phase ((2.99±0.41) mm vs. (5.66±1.57) mm, t=-5.34, P<0.001). The proportions of patients in remisson with Limberg score ≤2, normal wall layer stratification, and absence of fat wrapping were significantly higher than those of patients in active phase (10/10 vs. 34/98, 10/10 vs. 48/98, 10/10 vs. 41/98, Fisher′s exact test, P<0.001, =0.002, =0.001). BWT, Limberg score, wall layer stratification, and fat wrapping were positively correlated with MES ( r=0.676, 0.677, 0.441, and 0.493, all P<0.001). BWT and Limberg score were moderate positively correlated with C-hypersensitive reactive protein, erythrocyte sedimentation rate and fecal calprotectin (BWT: r=0.561, 0.420 and 0.458, all P<0.001; Limberg score: r=0.576, 0.469 and 0.403, all P<0.001), and were negatively correlated with serum albumin and hemoglobin (BWT: r=-0.604 and -0.453, both P<0.001; Limberg score: r=-0.573 and -0.532, both P<0.001). The results of ROC analysis showed that BWT achieved the best predictive efficacy in identifying endoscopic remission, and the best cut-off value was 3.45 mm (area under the curve was 0.972, 95% confidence interval: 0.944 to 1.000, P<0.001), with a sensitivity of 93.9% and specificity of 100.0%. Conclusions:TBUS parameters can accurately reflect disease activity in UC. It is a powerful tool for UC monitoring. The BWT<3.45 mm is the best cut-off value in prediction of endoscopic remission.

Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.

Objective:To explore the longitudinal predictive relationship between self-neglect and frailty among older adults.Methods:Data were drawn from the Chinese Longitudinal Healthy Longevity Survey conducted in 2011 (T1), 2014 (T2), and 2018 (T3). A total of 1 495 older adults aged≥65 years at T1 who participated in three consecutive surveys and had no missing key variables were included. General demographic information, self-neglect scores, and frailty status were extracted. Spearman correlation analysis was used to examine the association between self-neglect and frailty. Cross-lagged analysis was employed to investigate the potential causal relationship between the two variables.Results:The self-neglect scores for 1 495 older adults at T1, T2, and T3 were (2.84±1.39), (2.47±1.30), and (2.41±1.20), respectively, showing a declining trend. The frailty scores at T1, T2, and T3 were 0 (0, 1.00), 0 (0, 2.00), and 1.00 (0, 2.00), respectively, indicating an increasing trend. Cross-lagged analysis revealed that self-neglect at T1 positively predicted frailty at T2 (β=0.076, P=0.004). Frailty at both T1 and T2 positively predicted self-neglect at T2 (β=0.057, P=0.044) and T3 (β=0.058, P=0.029), respectively. Conclusions:Frailty among older adults positively predicts self-neglect, and self-neglect also has a certain predictive effect on frailty. Medical staff should strengthen early screening and intervention for frailty in older adults to delay the occurrence and progression of self-neglect.