BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.

ObjectiveTo investigate the possible mechanism of Wenyang Shengji Ointment （温阳生肌膏， WSO） in the treatment of diabetic wounds with yin syndrome. MethodsA total of 24 SD rats were randomly divided into a group （n=6） and modeling group （n=18）. The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection， full-thickness skin defects were created on the back of the rats to establish a diabetic wound with yin syndrome model. The normal group was fed with regular diet， and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups， the model group， the WSO group， and the Beifuxin （Recombinant Bovine Basic Fibroblast Growth Factor Gel， BX） group， 6 rats in each group. The WSO group was given the ointment to the wound， the Beifuxin group was givne BX gel， and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily for 14 days. Wound healing was recorded on days 0， 3， 7， and 14， and the wound healing rate was calculated on day 3， 7， and 14. On day 14 after treatment， HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha （HIF-1α） and vascular endothelial growth factor （VEGF）. Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue， and ELISA was used to detect the methylglyoxal （MGO） content in the wound tissue. ResultsCompared with the normal group， the model group showed poor wound healing on day 3， 7， and 14， with a low wound healing rate （P＜0.01）. HE staining showed scab coverage on the wound， with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced， while the relative protein levels of HIF-1α and the MGO content significantly increased （P＜0.01）， and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group， the WSO group and Beifuxin group showed better wound healing on day 3， 7， and 14， with an increased wound healing rate （P＜0.01）. The wound tissue showed clear and complete epithelial structure， reduced inflammatory cells， mature granulation tissue， and organized collagen arrangement. MGO content was significantly reduced （P＜0.01）. The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group， while only VEGF increased in the Beifuxin group （P＜0.05 or P＜0.01）. Compared with the Beifuxin group， the WSO group had a thicker epidermal layer， prominent collagen formation， significantly increased HIF-1α fluorescence expression， reduced MGO content in the wound tissue， and higher relative protein levels of HIF-1α （P＜0.05）. ConclusionWSO can reduce the accumulation of MGO in diabetic wound tissue with yin syndrome and activate the HIF-1α/VEGF pathway， which could be one of the mechanisms for promoting wound healing.

ObjectiveTo investigate the main risk factors for liver cirrhosis in chronic hepatitis B （CHB） patients with high metabolic risk， to establish a noninvasive predictive model， and to compare the diagnostic efficiency of this model and other models including fibrosis-4 （FIB-4）， aspartate aminotransferase-to-platelet ratio index （APRI）， gamma-glutamyl transpeptidase-to-platelet ratio （GPR）， and Forns index. MethodsA total of 527 CHB patients with high metabolic risks who were admitted to The Second Affiliated Hospital of Guangxi Medical University from September 1， 2017 to October 31， 2022 were enrolled as subjects， and they were randomly divided into modeling group with 368 patients and validation group with 159 patients at a ratio of 7∶3. The LASSO regression analysis and the multivariate Logistic regression analysis were performed for the modeling group to identify independent risk factors， and a nomogram model was established. The receiver operating characteristic （ROC） curve， the calibration curve， and the decision curve analysis were used to validate the nomogram prediction model in the modeling group and the validation group and assess its discriminatory ability， calibration， and clinical practicability. The Delong test was used to compare the area under the ROC curve （AUC） of the nomogram prediction model and other models. ResultsThe multivariate Logistic regression analysis showed that prealbumin （odds ratio ［OR］ = 0.993， 95% confidence interval ［CI］： 0.988 — 0.999， P= 0.019）， thrombin time （OR=1.182， 95% CI： 1.006 — 1.385， P=0.047）， log₁₀ total bilirubin （TBil） （OR=1.710， 95%CI： 1.239 — 2.419， P=0.001）， and log₁₀ alpha-fetoprotein （AFP） （OR=1.327， 95%CI： 1.052 — 1.683， P=0.018） were independent influencing factors for liver cirrhosis in CHB patients with high metabolic risks. A nomogram model for risk prediction was established based on the multivariate analysis， which had an AUC of 0.837 （95%CI： 0.788 — 0.888）， a specificity of 73.5%， and a sensitivity of 84.7%， as well as a significantly higher diagnostic efficiency than the models of FIB-4 （0.739）， APRI （0.802）， GPR （0.800）， and Forns index （0.709） （Z=2.815， 2.271， 1.989， and 2.722， P=0.005， 0.017， 0.045， and 0.006）. ConclusionThe nomogram model established based on prealbumin， thrombin time， log₁₀ TBil， and log₁₀ AFP has a certain clinical application value.

AIM: To investigate the clinical efficacy of pars plana vitrectomy(PPV)combined with fovea-sparing internal limiting membrane(ILM)peeling and silicone oil(SO)tamponade for treating pathological myopic foveoschisis(PMF).METHODS:This study is a retrospective observational analysis of 10 cases(10 eyes)diagnosed with PMF that underwent PPV with fovea-sparing ILM peeling and SO tamponade between January 2023 and November 2024. The best-corrected visual acuity(BCVA), central foveal thickness(CFT), foveoschisis(FS), and the detachment and reattachment of FS and macular fovea were assessed preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS:Among the 10 cases of PMF patients(10 eyes), the complete reattachment rate was 30%(3 eyes), while partial reattachment was observed in 70%(7 eyes). At 3 mo postoperatively, BCVA(LogMAR)was significantly improved to 0.957±0.393 compared with 1.432±0.509 before surgery(P<0.05), and both CFT(437.9±180.4 vs. 207.5±76.1 μm)and FS(686.5±172.2 vs. 290.7±86.6 μm)showed significant decreases(P<0.05). No complications such as macular hole, retinal detachment, silicone oil emulsification, or endophthalmitis were observed during the surgery or throughout the follow-up period.CONCLUSION:PPV with SO tamponade and fovea-sparing ILM peeling has been demonstrated to facilitate both visual acuity improvement and anatomical reattachment in cases of PMF.

OBJECTIVE To investigate the potential mechanism of berberine improving diabetes mellitus type 2 （T2DM） combined with metabolic-associated fatty liver disease （MAFLD） by regulating ceramide. METHODS Thirty-two db/db mice with blood glucose levels＞11.1 mmol/L （T2DM model） were divided into four groups： model group， berberine low- and high-dose groups [100， 200 mg/（kg·d）] and metformin group [300 mg/（kg·d）]， with 8 mice in each group. Additionally， 8 wt/wt mice were selected as the normal control group. Mice in each group were administered the corresponding drug solution or water by gavage once daily for a continuous period of 6 weeks. During the experiment， the body weight of the mice was monitored， and the differences in final body weight were analyzed. After the last administration， the body shape of the mice in each group was observed， and their fasting blood glucose （FBG） and the lipid indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] were measured. Fasting serum insulin （FINS） levels were also measured， and the insulin resistance index HOMA-IR） and insulin sensitivity index （ISI） were calculated. Liver weight， liver index and serum liver function indicators [alanine transaminase （ALT）， aspartate transaminase（AST）] were assessed， and hepatic histopathological changes were observed. Additionally， the expression of fatty acid synthesis-related proteins [sterol regulatory element-binding protein 1 （SREBP1）， fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）] in liver tissue was examined. Serum samples from the normal control group， model group， and berberine high-dose group were collected for non-targeted lipidomics analysis and validation. RESULTS Compared with the model group， the pathological changes， including disordered liver tissue cell arrangement and lipid vacuoles， were significantly improved in the berberine low- and high-dose groups. The significant decreases or down-regulations were observed in body weight in the last week， as well as FBG， TC， TG， and LDL-C levels， HOMA-IR （except for the berberine low-dose group）， liver weight， liver index， AST and ALT levels， and protein expressions of SREBP1， FASN and ACC1. Additionally， HDL-C levels， FINS （except for the berberine high-dose group）， and ISI （except for the berberine low-dose group） were significantly increased （P＜0.05）. A total of 21 potential differential metabolites， including multiple types of ceramides， were identified； these metabolites were primarily enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Verification experiments confirmed that high-dose berberine significantly reduced the serum content of ceramide in model mice （P＜0.05）. CONCLUSIONS Berberine reduces insulin resistance， improves liver damage and lipid accumulation in the T2DM combined with MAFLD mice， and these effects may be related to the reduction of ceramide content.

Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

Objective: To analyze the association of mother-child interaction and screen exposure of preschool children with psychological and behavioural problems, so as to provide guidance for promoting the psychological development of preschool children. Methods: From November to December 2024, a convenience cluster sampling method was used to survey 2 977 mothers of preschool children in Daguan and Yingjiang districts of Anqing City. The Chinese Parent-Child Interaction Scale (CPCIS) was applied to evaluate the quality of mother-child interaction, and the Conners Parent Symptom Questionnaire (PSQ) was used to assess the psychological and behavioral problems of preschool children. Binary Logistic regression was applied to analyze the association of mother-child interaction, screen exposure and their combined effect on psychological and behavioral problems among preschool children. Results: The detection rate of psychological and behavioral problems among preschool children was 13.9%. Binary Logistic regression results showed that low scores of mother-child interaction ( OR=2.31, 95%CI =1.72-3.11) and high screen exposure ( OR= 1.52 , 95%CI =1.23-1.88) were higher risks for psychological and behavioral problems in preschool children; the results of the combined effect showed that preschool children in low scores of mother-child interaction and low screen exposure group ( OR=2.18, 95%CI =1.46-3.28), low scores of mother-child interaction and high screen exposure group ( OR=3.13, 95%CI =2.10- 4.65 ) had significantly higher risks of abnormal detection in psychological and behavioral problems, compared to those in the high scores of mother-child interaction and low screen exposure group respectively (all P <0.05). Conclusions Both screen exposure and mother- child interaction are associated with psychological and behavioral problems in preschool children. High quality mother-child interaction can relieve the adverse effects of screen exposure on preschool children s psychological and behavioral development.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins