Objective To analyze the differences in the efficacy and safety between antibody-drug conjugate(ADC)combined with programmed cell death 1(PD-1)inhibitor and chemotherapy in the treatment of advanced bladder cancer based on real-word data, so as to provide reference for individualized treatment regimens. Methods Clinical data of 107 patients pathologically diagnosed with bladder urothelial carcinoma admitted to our hospital during Jan.13, 2022 and Dec.27, 2024 were retrospectively collected. All patients had lymph node and/or distant metastases confirmed by CT or PET/CT. Among them, 38 were treated with Disitamab Vedotin plus Toripalimab(Disitamab Vedotin group), and 69 were treated with Gemcitabine plus Cisplatin(GC, chemotherapy group). The short and long-term efficacy and treatment-related adverse events(TRAEs)were compared between the two groups. Results The objective response rate(ORR)was higher in the Disitamab Vedotin group than in the chemotherapy group(18.4% vs. 5.8%), with no statistically significant difference(P＞0.05). The disease control rate(65.8% vs. 33.3%), progression-free survival(9.35 months vs. 7.76 months)and overall survival(29.54 months vs. 12.33 months)were higher/longer in the Disitamab Vedotin group than in the chemotherapy group, with statistically significant differences(P＜0.05). TRAEs such as peripheral neuropathy(44.7%)and alopecia(36.8%)occurred in 35 patients(92.1%)in the Disitamab Vedotin group, while TRAEs including leukopenia(44.9%), nausea and vomiting(44.9%), and alopecia(42.0%)occurred in 65 patients(95.6%)in the chemotherapy group. Conclusion Compared with standardized chemotherapy, Disitamab Vedotin plus Toripalimab can significantly reduce the risk of disease progression or death in patients with advanced bladder cancer, with manageable safety.

Objective To investigate the expression and clinical significance of Claudin-6(CLDN6),tripartite motif-containing protein 59(TRIM59)and chemokine-like factor-like MARVEL transmembrane domain containing member 6(CMTM6)in nasopharyngeal carcinoma(NPC)tissue.Methods A total of 135 NPC patients were selected as the study objects,and cancer tissue(observation group)and para-cancer tissue(control group)of all patients were collected.All patients were followed up for 3 years.According to the follow-up results,93 surviving patients were included in the survival group and 42 dead patients were included in the death group.The mRNA expressions of CLDN6,TRIM59 and CMTM6 were determined by fluorescence quantitative PCR.Multivariate Cox regression was used to analyze the influencing factors of death in NPC patients.Kaplan-Meier method was used to analyze the relationship between the expression levels of CLDN6,TRIM59,CMTM6 and the prognosis of NPC patients.Results Compared with the control group,mRNA expressions of CLDN6,TRIM59 and CMTM6 were increased in the observation group(P＜0.05).There were no significant differences in age,sex,body mass index,TNM stage,bone metastasis,smoking history,drinking history and hypertension history between the survival group and the death group.Compared with the survival group,the proportion of NPC family history and the mRNA expression of CLDN6,TRIM59 and CMTM6 in cancer tissue were increased in the death group(P<0.05).Multivariate Cox regression analysis showed that the increased levels of CLDN6,TRIM59 and CMTM6 in cancer tissue were influential factors for death of NPC patients(P＜0.05).According to the mean expression levels of CLDN6,TRIM59 and CMTM6 mRNA in cancer tissue,patients were divided into the low expression group and the high expression group.The 3-year survival rate of the high expression group was significantly lower than that of the low expression group(P＜0.05).Conclusion The mRNA expressions of CLDN6,TRIM59 and CMTM6 in NPC tissue are significantly increased,which is a risk factor for death in NPC patients,and the mRNA expressions of CLDN6,TRIM59 and CMTM6 are correlated with the prognosis of patients.

Objective To investigate the expression and clinical significance of Claudin-6(CLDN6),tripartite motif-containing protein 59(TRIM59)and chemokine-like factor-like MARVEL transmembrane domain containing member 6(CMTM6)in nasopharyngeal carcinoma(NPC)tissue.Methods A total of 135 NPC patients were selected as the study objects,and cancer tissue(observation group)and para-cancer tissue(control group)of all patients were collected.All patients were followed up for 3 years.According to the follow-up results,93 surviving patients were included in the survival group and 42 dead patients were included in the death group.The mRNA expressions of CLDN6,TRIM59 and CMTM6 were determined by fluorescence quantitative PCR.Multivariate Cox regression was used to analyze the influencing factors of death in NPC patients.Kaplan-Meier method was used to analyze the relationship between the expression levels of CLDN6,TRIM59,CMTM6 and the prognosis of NPC patients.Results Compared with the control group,mRNA expressions of CLDN6,TRIM59 and CMTM6 were increased in the observation group(P＜0.05).There were no significant differences in age,sex,body mass index,TNM stage,bone metastasis,smoking history,drinking history and hypertension history between the survival group and the death group.Compared with the survival group,the proportion of NPC family history and the mRNA expression of CLDN6,TRIM59 and CMTM6 in cancer tissue were increased in the death group(P<0.05).Multivariate Cox regression analysis showed that the increased levels of CLDN6,TRIM59 and CMTM6 in cancer tissue were influential factors for death of NPC patients(P＜0.05).According to the mean expression levels of CLDN6,TRIM59 and CMTM6 mRNA in cancer tissue,patients were divided into the low expression group and the high expression group.The 3-year survival rate of the high expression group was significantly lower than that of the low expression group(P＜0.05).Conclusion The mRNA expressions of CLDN6,TRIM59 and CMTM6 in NPC tissue are significantly increased,which is a risk factor for death in NPC patients,and the mRNA expressions of CLDN6,TRIM59 and CMTM6 are correlated with the prognosis of patients.

Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury，so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge，there were 9 cases of self-catheterization，19 cases of intermittent catheterization，22 cases of reflexive voiding，26 cases of long-term catheterization，and 2 cases using urinary collector.At the end of follow-up，there were 15 cases of self-catheterization，8 cases of intermittent catheterization，34 cases of reflexive voiding，14 cases of long-term catheterization，and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ =21.43，P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be answered.By merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+cells within M1.These PRX1+cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation.Deeper into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1+cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway.The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1.Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs.These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

AIM:To explore the role and molecular mechanism of Men1 gene in regulating mouse renal fibro-sis.METHODS:A unilateral ureteral obstruction(UUO)-induced renal fibrosis model was established using C57BL/6 mice,and the mice were randomly divided into 4 groups:sham,UUO-3 d,UUO-7 d,and UUO-14 d,with 15 mice in each group.The C57BL/6 mice with Men1 knockout were randomly divided into 4 groups:sham-Men1-WT,sham-Men1-CKO,UUO-Men1-WT,and UUO-Men1-CKO,with 8 mice in each group.HE staining,Masson staining,and Sirius red staining were used to detect UUO-induced renal injury and renal fibrosis.Human renal tubular epithelial HK-2 cells with MEN1 knockout were constructed.RT-qPCR,Western blot,immunohistochemistry and immunoflurorescnence were per-formed to detect the mRNA and protein expression of MEN1,fibrosis markers(α-smooth muscle actin,collagen type Ⅲ and fibronectin 1)and m6A-related proteins[methyltransferase-like 3(METTL3),METTL14,YTH domain family pro-tein 2(YTHDF2),AlkB homolog 5(ALKBH5),and fat mass and obesity-associated protein(FTO)]in UUO mouse kid-ney tissues and transforming growth factor-β(TGF-β;10 μg/L)-treated HK-2 cells.Dot blot analysis was conducted to measure m6A methylation levels in both mouse kidney tissuess and HK-2 cells.RESULTS:The expression of Men1 de-creased with the aggravation of renal fibrosis(P＜0.01).Men1 inhibited the expression of fibrosis markers in renal tis-sues,and MEN1 knockout increased the accumulation of collagen induced by UUO and TGF-β(P＜0.01).The expres-sion of FTO and ALKBH5 in mouse kidney tissues and HK-2 cells was down-regulated by MEN1 knockout(P＜0.01),and the methylation level of m6A was increased(P＜0.01).Overexpression of FTO significantly reduced the accumulation of m6A modifications and renal fibrosis caused by MEN1 loss,and the methylation level of m6A was increased(P＜0.01).CONCLUSION:Loss of Men1 gene promotes renal fibrosis in mice,and Men1 suppresses renal fibrosis in mice by pro-moting the expression of FTO/ALKBH5 to reduce m6A modifications.

To construct a single-cell transcriptomic map of testicular tissue under hypobaric hypoxia exposure and perform diversity analysis of supportive cells, aiming to provide new insights into the mechanisms of reproductive toxicity for future research.