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 epidemiological characteristics and control measures of dengue fever in Zhongshan City in 2024, so as to provide insights into optimization of dengue fever control strategies in the city. Methods Data pertaining to dengue fever cases in Zhongshan City in 2024 were collected from the Infectious Disease Reporting System of China Disease Prevention and Control Information System, and the epidemiological characteristics of the cases were analyzed using a descriptive statistical method. The density of Aedes albopictus mosquito was monitored across all 23 townships (subdistricts) using Breteau index (BI) and mosquito ovitrap index (MOI) at midmonth each month from March to December 2024. In addition, the climatic characteristics, case reporting patterns, and corresponding control measures were analyzed during different phases of dengue fever epidemics in Zhongshan in 2024. Furthermore, real-time quantitative reverse transcription PCR (RT-qPCR) assay was employed to serotype the dengue virus among local dengue fever cases with unknown sources of infections. The dengue virus envelope (E) gene was sequenced using Sanger sequencing among dengue fever cases without apparent epidemiological links. A phylogenetic tree was constructed using the neighbor-joining method to infer major transmission chains during the dengue fever epi demics. Results A total of 952 dengue fever cases were reported in Zhongshan City in 2024, including 879 local cases, 57 domestically imported cases from other regions, and 16 overseas imported cases, representing the largest outbreak in nearly two decades. The first local dengue fever case was reported on July 5, and the last one was detected on December 19, with all townships and subdistricts affected. Mosquito monitoring data indicated that both MOI and BI rose rapidly from March to May, and then remained at high levels with fluctuations, and began to decline in October. The dengue fever epidemic was categorized into five distinct phases in Zhongshan, including non-epidemic, pre-epidemic, early-epidemic, peak, and receding stages. During the pre-epidemic and early-epidemic phases, key measures included enhancing sensitivity of case detection, implementing isolation and treatment of hospitalized cases, and carrying out standardized vector control measures in affected communities. In the peak phase, the strategy shifted towards targeted mosquito control in key communities and clinical rescue and treatment emphasized on “preventing severe cases and deaths”. Among 481 local cases with unknown sources of infections, RT-qPCR assay revealed that 68.8% (331/481) were infected with dengue virus type I and 31.2% (150/481) with type II among local dengue fever cases in Zhongshan City in 2024. Phylogenetic analysis revealed two major transmission chains: one originating from imported cases within Guangdong Province around Zhongshan City, and another from cases imported from Malaysia. Late detection of local dengue fever cases contributed to widespread community outbreaks. Conclusions The 2024 dengue fever epidemic in Zhongshan City was of considerable scale, which was primarily driven by imported cases from overseas and surrounding regions, leading to local community outbreaks. The epidemic began in early July, increased rapidly during August and September, peaked in October, and subsequently declined, with a trend consistent with the average pattern observed in previous high-incidence years. By implementing differentiated control measures tailored to each phase of the epidemic, the local transmission of dengue fever was successfully contained in Zhongshan City in 2024.

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

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.

According to the pathological changes of cervical cancer， it is believed that traditional Chinese medicine can effectively prevent and treat through the following three stages. Firstly， during the stage of persistent high-risk human papilloma virus （HR-HPV） infection， the state before disease arises， it is advisable to prevent from arises. The disease mechanism of this stage is liver constraint and spleen deficiency， damp-turbidity retention， and modified Wandai Decoction （完带汤） can be used strengthen the spleen and soothe the liver， boost qi and dispel dampness. Secondly， at low-grade squamous intraepithelial lesions （LSIL） of the uterine cervix with persistent HR-HPV infection stage， the disease state， should control the development of existing disease， and the disease mechanism of this stage is depletion of qi and blood， combined with dampness and stasis. Modified Danggui Shaoyao Powder （当归芍药散） can be used to strengthen spleen， soften liver， promote blood circulation and drain water. Thirdly， after the surgery treatment of cervical precancerous lesions or cervical cancer， the post-treatment state， it is advisable to "prevent recurrence after treatment"， and the disease mechanism of this stage is co-existing of deficiency， stasis， and dampness with a small amount of cancer toxin. Prescriptions of modified Danggui Shaoyao Powder and Fangji Fuling Decoction （防己茯苓汤） can be used to boost qi， warm yang， invigorate blood and drain water， and also resolve toxins.

BACKGROUND:Changes in skeletal muscle mass have been indicated in studies addressing the effects of low-frequency pulsed magnetic fields on the structure and morphology of the skeletal muscle,but no relevant studies have been conducted on the morphologic changes that occur after chronic exposure to the low-frequency pulsed magnetic field. OBJECTIVE:To observe the effects of chronic exposure to low-frequency pulsed magnetic fields on the maximal voluntary contraction and morphologic indicators of the quadriceps muscle of the leg,thereby providing a reference of muscle morphologic changes for the use of this technique as a strategy for muscle function improvement. METHODS:Seventy healthy subjects were recruited and randomly divided into a test group that received magnetic field stimulation and a control group that underwent sham treatment,with 35 subjects in each group,and the total duration of the trial was 4 weeks.The test group underwent low-frequency pulsed magnetic stimulation for 15 minutes every 48 hours,while the control group underwent sham treatment,with the same intervention interval and duration as the test group.After 4 weeks of intervention,changes in the maximum voluntary contraction value of the quadriceps muscle in different groups were observed,and B-mode ultrasonography was utilized as a means of assessment to observe changes in muscle thickness,muscle cross-sectional area,and pinnation angle indexes. RESULTS AND CONCLUSION:After 4 weeks of chronic exposure to low-frequency pulsed magnetic fields,68 subjects completed the test.The maximum voluntary contraction value of the quadriceps muscle in the test group increased significantly(P=0.000),and the increment was significantly higher than that of the control group(P=0.008).Three indexes related to muscle morphology in the test group were significantly higher than the pre-test values(P=0.000),while in the control group,muscle thickness showed a significant reduction(P=0.020),there was no significant change in the pinnation angle,but a significant increase in the cross-sectional area(P=0.000).Intergroup comparisons revealed that the three indicators related to muscle morphology,including muscle thickness(P=0.012),pinnation angle(P=0.003),and cross-sectional area(P=0.049),were significantly higher in the test group than in the control group.The above data confirmed that the maximum voluntary contraction of the quadriceps muscle was significantly increased in healthy adults after 4 weeks of chronic exposure to the low-frequency pulsed magnetic field,and significant increases in the three muscle morphometric indices of muscle thickness,cross-sectional area,and pinnation angle were observed in the test group,providing a basis of muscle tissue morphology for the use of this technique as an exercise alternative and medical treatment strategy for muscle improvement.

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 evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment.Methods:This retrospective, multicenter, single-arm, pre–post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m2, and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups.Results:In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923–0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions:FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.