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.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

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.

BackgroundChronic insomnia is characterized by a prolonged and recurrent course. The efficacy of repeated transcranial magnetic stimulation （rTMS） as a physical therapy method to improve sleep quality remains inadequately supported by evidence， particularly regarding its relationship with personality traits. ObjectiveTo explore the efficacy and influencing factors of rTMS in the treatment of chronic insomnia， and to provide insights into its therapeutic potential. MethodA total of 46 patients who met the diagnostic criteria for chronic insomnia according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and were treated at the Third Hospital of Mianyang from September 2022 to September 2023 were selected. Prior to treatment， participants underwent assessments using the Eysenck Personality Questionnaire （EPQ）， Hamilton Depression Scale-17 item （HAMD-17） and Hamilton Anxiety Scale （HAMA）. The Pittsburgh Sleep Quality Index （PSQI） was used to assess sleep quality before treatment， at the end of the second week of treatment and one week post-treatment. ResultsAt the end of the second week of treatment， patients exhibited significantly improved total PSQI score and subscale scores related to subjective sleep quality， sleep latency， sleep duration， sleep efficiency， sleep disturbance and daytime dysfunction （t=4.755~13.361， P<0.01）， with 24 cases （54.35%） showing effective treatment outcomes. Multiple linear regression analysis showed that introverted and extroverted personality traits contributed significantly to the regression equation （B=0.317， P<0.01）， explaining 29.90% of the total variation （R²=0.299）. ConclusionrTMS treatment may effectively improve the sleep quality of patients with chronic insomnia， with its therapeutic effect appearing to associated with introverted and extroverted personality traits. ［Funded by National Natural Science Project of China （number， 82372080）］

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for circular superficial esophageal cancer.Methods:A retrospective analysis was conducted on 74 consecutive cases of circular superficial esophageal squamous cell carcinoma treated with ESD at Nanjing Drum Tower Hospital from January 2015 to December 2019. The success rate of ESD, curative resection rate, incidence of complications, and additional treatment were mainly observed.Results:One case was transferred to surgery, and the remaining 73 cases successfully completed ESD treatment. The success rate of ESD was 98.6%. Postoperative pathology of ESD revealed that 39 cases achieved curative resection, with a curative resection rate of 53.4% (39/73). Intraoperative muscle layer injury occurred in 15 cases (20.5%), and intraoperative perforation occurred in 1 case (1.4%). Two cases (2.7%) experienced delayed bleeding, and one case (1.4%) experienced delayed perforation. Eleven cases were lost to follow-up, and the remaining 62 cases received follow-up for 36.4±19.0 months. Among the follow-up cases, 12 underwent additional surgery and 5 cases additional chemotherapy and radiotherapy. Among the 57 patients with follow-up data who did not underwent surgery, 49 developed esophageal stenosis after ESD, with an incidence rate of 86.0%.Conclusion:ESD for circular superficial esophageal cancer is generally safe, but it is prone to muscle layer injury during the operation, with a low curative resection rate, a high incidence of postoperative esophageal stenosis, and a high proportion of additional surgical procedures.

Objective:To establish a sensing technology of catalytic hairpin self-assembly (CHA) combining with clustered interspaced short palindromic repeats with associated protein 12a (CRISPR-Cas12a) for the detection of exosomal microRNA-21 (miR-21), and to analyze the performance.Methods:Eight patients diagnosed as breast cancer in the First Affiliated Hospital of the Army Military Medical University from September to October 2023 were selected as the breast cancer group; 8 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group. Plasma exosomes and their miR-21 were extracted using the kit. DNA hairpins and CRISPR RNA sequences were designed for miR-21 sequences. The feasibility of detection technology was validated using polyacrylamide gel electrophoresis and fluorescence spectrophotometer. Hairpins concentration, CHA reaction time, Cas12a protein concentration and Cas12a protein reaction time were further optimized. On this basis, miR-21 was detected at different concentrations (0, 0.1, 0.5, 1.0, 2.5, 5.0, 7.5, 10.0 nmol/L), and fluorescence intensity was collected for unary linear regression analysis to evaluate methodological sensitivity; meanwhile, different types of miRNAs (miR-31, miR-26a, miR-192, miR-25-3p) and blank controls were detected to evaluate methodological specificity. A case-control study was conducted to detect the relative expression level of plasma exosomal miR-21 in breast cancer group and healthy control group using this detection technology and reverse transcription PCR (RT-PCR) to evaluate the detection ability of clinical samples.Results:A detection method for exosomal miR-21 was established using CHA combining with CRISPR-Cas12a. The concentration of miR-21 detected by this method showed a good linear relationship with fluorescence intensity (the linear correlation coefficient 0.966 7), and the linear detection range was 0.1-10.0 nmol/L, and the detection limit was 87.81 pmol/L. The fluorescence intensity of miR-21 was 450.27±23.96 which was higher than that of miR-31, miR-26a, miR-192, miR-25-3p, and the blank group (98.89±7.35, 98.12±2.07, 98.93±2.45, 96.66±2.45, 82.93±3.54, respectively), with statistical significance ( P<0.001). The results of RT-PCR showed that the relative expression levels of plasma exosomal miR-21 in the breast cancer group were higher than that in healthy control group (1.83±0.27 vs 0.93±0.12, P<0.001); CHA combining with CRISPR-Cas12a detection technology showed that the relative expression levels of plasma exosomal miR-21 in breast cancer group were higher than that in healthy control group (1.94±0.21 vs 0.98±0.08, P<0.001); There was no significant difference in the relative expression levels of plasma exosomal miR-21 between CHA combining with CRISPR-Cas12a detection technology and reverse transcription PCR in breast cancer group and healthy control group ( P>0.05). Conclusion:In this study, a highly sensitive and specific sensing technology of CHA combining with CRISPR-Cas12a for exosomal miR-21 was established. The results of detecting plasma exosomal miR-21 were consistent with the results of reverse transcription PCR, which can be used for screening of breast cancer patients.

Objective Based on a novel type of cell death induced by disulfide stress,known as disulfidptosis,this study explores the role of long non-coding RNA(LncRNA)in gastric cancer and establishes a prognosis model re-lated to disulfidptosis,providing a new method for assessing the prognosis of gastric cancer treatment.Methods Transcriptomic data from gastric cancer and normal tissue samples were obtained from the public database TCGA,and disulfidptosis-related LncRNAs were selected through Pearson analysis and LASSO-Cox regression analysis.A relevant prognostic model for gastric cancer was constructed based on the above LncRNAs and validated by function-al enrichment analysis,tumour microenvironment and immune cell infiltration analysis,drug sensitivity analysis and quantitative reverse transcription PCR(RT-qPCR).Results In this study,400 disulfide death-associated LncR-NAs were identified and five of them were screened to construct a prognostic model for assessing the prognosis of gastric cancer patients.The models showed in validation that the survival of the high-risk score group was shorter than that of the low-risk score group(P＜0.05).In addition,the predictive ability of the prognostic model(AUC=0.725)was better than that based only on basic characteristics such as age and gender.The expression levels of disulfide death-associated LncRNAs differed between normal and gastric cancer tissues(P＜0.001).Conclusion The disulfidptosis-related LncRNA prognosis model developed in this study can effectively assess the prognosis of gastric cancer patients and the tumor microenvironment,providing potential targets and a theoretical basis for new immunotherapeutic strategies for gastric cancer.

bjective　To analyze the drug resistance screening status and drug resistance influencing factors of high-risk groups of drug-resistant pulmonary tuberculosis in Qingdao, and to understand the inclusion of rifampicin patients in treatment, so as to provide a reference for the prevention and treatment of drug-resistant pulmonary tuberculosis. Methods　The medical records of 726 cases of drug-resistant pulmonary tuberculosis among high-risk populations registered in Qingdao from 2018 to 2022 were obtained from the National Health Insurance Information System of the China Center for Disease Control and Prevention. The drug resistance to five anti-tuberculosis drugs, namely isoniazid (INH), rifampicin (RFP), ethambutol (EMB), levofloxacin (Lfx), and amikacin (Am), in the high-risk populations of drug-resistant pulmonary tuberculosis was analyzed. Univariate and multivariate logistic regression were used toidentify factors influencing rifampicin resistance, and the detection and inclusion of treatment for rifampicin-resistant patients were evaluated. Results　Of the 726 subjects, 278 were drug-resistant, with a total drug resistance rate of 38.29%. The drug resistance for the five anti-tuberculosis drugs in descending order was: INH 25.90%(188/726), RFP 22.87%(166/726), Lfx 14.19%(103/726), EMB 11.29%(82/726), Am 2.48%(18/726). Analysis of the drug resistance spectrum showed that among those resistant to one drug, RFP was most common, accounting for 13.67% (38/278); among those resistant to two drugs, INH+RFP was predominant, accounting for 15.83% (44/278); among those resistant to three drugs, INH+RFP+Lfx was most frequent, at 7.19% (22/278); and among those resistant to four drugs, INH+RFP+EMB+Lfx was highest, at 6.12% (17/278). Multivariate logistic regression analysis of rifampicin resistance showed that compared with patients under 25 years of age, the risk of developing rifampicin resistance was lower in the groups aged 45 to under 65 and those aged 65 and above (OR=0.356, 95%CI: 0.181-0.700; OR=0.352, 95%CI: 0.170-0.729). Compared with migrant patients in other provinces, local patients from within the same county or district had a lower risk of developing rifampicin resistance (OR=0.599, 95%CI:0.383-0.962). Compared with patients who were smear-positive at the end of the second month of initial treatment, the risk of developing rifampicin resistance was higher in patients with relapse/return, failure of retreatment/chronic, and other categories of patients (OR=9.380, 95%CI:3.717-23.671;OR=25.749, 95%CI:8.037-82.490; OR=36.651, 95%CI:8.438-159.201). Conclusions　The situation of drug-resistant pulmonary tuberculosis in Qingdao cannot be ignored. Individuals under 25 years old, migrants from other provinces, and patients with relapse/return, failure of retreatment/chronic, and other categories are significant risk factors for developing rifampicin resistance in the high-risk groups of drug-resistant pulmonary tuberculosis.