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.

Hepatitis B is a major global public health issue. Through the implementation of comprehensive prevention and control strategies centered on hepatitis B vaccination， China has achieved remarkable progress in hepatitis B prevention and control， while there are still many issues and challenges. This article reviews the development of hepatitis B vaccination strategies in China， analyzes the goal and advances in vaccination in different populations， and problems and challenges， in order to provide a reference for further optimizing vaccination strategies and improving the levels of prevention and control.

Comprehensive occupational hazard risk assessment in employers is a core component of the pilot program for occupational health classification supervision and law enforcement. The quality and effectiveness of classification-based supervision are directly affected by both the assessment process and its outcomes. However, several issues have emerged since the implementation of the pilot program on the comprehensive risk assessment, including an excessive number of self-assessment items, lack of implementation basis for certain self-assessment items, misinterpretation for certain self-assessment items, inconsistencies between evaluation criteria and existing standards, incomplete implementation of some items, omission of comprehensive risk assessment elements, unclear definitions of key industries and key occupational hazards, and inconvenient assessment procedures on comprehensive risk assessment. To enhance the applicability, accuracy, and objectivity of the comprehensive risk assessments conducted by employers, it is recommended to optimize self-assessment items, standardize risk assessment content, tailor comprehensive risk assessments to actual workplace conditions, refine the identification of key industries and key occupational hazards, improve comprehensive risk assessment methodologies, and establish clear grading rules for the comprehensive risk assessment.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Objective:The study aimed to analyze the risk variables influencing the prognosis of patients with sepsis-associated delirium (SAD) in the Intensive Care Unit (ICU) and build a prediction nomogram.Methods:This was a retrospective cohort study that includes patients with SAD in the Medical Information Mart for Intensive CareⅢ database (MIMIC-Ⅲ) database as training cohort, and patients who were hospitalized in the First Hospital of Jiaxing from January 2021 to September 2022 as validation cohort. Inclusion criteria: (1) age≥18 years old; (2) being admitted to the ICU for the first time; (3) the length of ICU stay≥24 h; (4) consistent with the diagnosis of sepsis; (5) the diagnosis of delirium was identified by CAM-ICU questionnaire. The general information, vital signs, past medical history and laboratory examination results of the patients were collected, and the outcome was 28-day mortality. Multiple logistic regression was used to identify independent influencing factors and the nomogram was constructed. The validity of the prediction model was determined using multiple indicators, including calibration curve, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and Hosmer-Lemeshow test.Results:A total of 250 patients were included in the training cohort and 154 patients were in the validation cohort. The multiple logistic regression demonstrated that age ( OR=1.057, 95% CI: 1.030-1.084, P<0.001), respiratory frequency ( OR=1.117, 95% CI: 1.037-1.202, P=0.003), lactic acid ( OR=1.137, 95% CI:1.011-1.279, P=0,032), hemoglobin ( OR=0.983, 95% CI: 0.970-0.997, P=0.020), SOFA score ( OR=1.184, 95% CI: 1.070-1.309, P=0.001) were independent risk factors associated with the 28-day mortality of patients with SAD. The AUC of the nomogram created by the five factors above was 0.773 (95% CI: 0.705-0.841), and the Hosmer-Lemeshow test showed that the model was a good fit ( P=0.875). The DCA curve indicates that the model has potential net benefit. The AUC was 0.864 (95% CI: 0.799-0.928) in the validation cohort, and the Hosmer-Lemeshow test showed that the model was a good fit ( P=0.488). The DCA curve indicates that the model of the validation cohort had potential net benefit. Conclusion:The prediction model based on age, respiratory frequency, lactate, hemoglobin, and SOFA scores shows valuable capability of predicting the prognosis of patients with SAD, which could help clinicians identify risk factors at first time and make earlier intervention.

Rosacea is a chronic facial inflammatory skin disease. It has been proved that heredity, immunity, neurovascular disorders, microorganisms, skin barrier damage and ultraviolet rays are closely related to the occurrence of rosacea. However, the exact pathogenesis of rosacea has not been fully elucidated. This review summarizes recent advances in the pathogenesis of rosacea in the past 5 years.

ObjectiveTo investigate the current status and influencing factors of hand hygiene practices among primary healthcare workers， and to provide a reference for improving hand hygiene behavior in primary healthcare institutions. MethodsA self-designed questionnaire was used to conduct a survey among medical staff of seven community health service centers in Jiading District， Shanghai， using a cluster random sampling method. The data collected were subjected to descriptive statistics， reliability and validity tests， correlation analysis， and structural equation model fitting. ResultsA statistical difference in hand hygiene compliance was found among medical staff with varying occupational types and educational levels （P<0.05）， and medical staff in clinical departments exhibited higher levels of hand hygiene compliance （P<0.05）. In the health belief model， among the core variables， healthcare workers’ perceived benefits， perceived barriers， and self-efficacy had a direct impact on hand hygiene behavior， with direct effect values of 0.341， -0.152， and 0.234， respectively. Meanwhile， cues to action and perceived severity of COVID-19 infection indirectly affected hand hygiene behavior， with an indirect effect value of 0.066 and 0.062， respectively. ConclusionHealthcare workers generally exhibit a high degree of hand hygiene compliance， but there are variations in hand hygiene scores among healthcare workers with different characteristics. Enhancing healthcare worders’ perception of benefits， action cues， and self-efficacy while reducing perceived barriers can effectively improve their hand hygiene behavior.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.