1.Expression of Matrix Metalloproteinase-7 and-19 in Liver Tissues of Rats with Biliary Atresia
Journal of China Medical University 2017;46(12):1071-1075,1081
Objective To detect the expression of matrix metalloproteinase (MMP)-7 and MMP-19 in the liver tissue of young rat models with biliary atresia (BA) and to explore their roles in progressive fibrosis.Methods Totally 132 Wistar newborn rats were subjected to common bile duct ligation (BDL) at day 3 after birth to establish animal models of biliary atresia.Sixty-two young rats served as the control group.Liver tissues were collected at days 3,7,14,21,and 28.Immunohistochemistry,Western blotting,and RT-PCR were used to detect the expression of MMP-7 and MMP-19.Results The BA models manifested cholestasis as early as 24 h after BDL.HE and Masson staining revealed progressive hepatic fibrosis.The expression of MMP-7 was observed to increase with time and was significantly higher in the experimental group when compared to control.The expression of MMP-19 was also found to gradually increase with time;however,it was lower than the control group.Conclusion MMP-7 and MMP-19 may be involved in the fibrosis of biliarv atresia.
2.Effect of the number of retrieval attempts on the outcomes after successful recanalization of mechanical thrombectomy in patients with acute ischemic stroke
Guangxin DUAN ; Xi ZHANG ; He ZHANG ; Tingzheng ZHANG ; Yun LUO ; Yun XU ; Jingwei LI
International Journal of Cerebrovascular Diseases 2022;30(4):247-252
Objective:To investigate the effect of the number of retrieval attempts on the outcomes after successful recanalization of mechanical thrombectomy in patients with acute ischemic stroke.Methods:Patients with acute large vessel occlusive ischemic stroke underwent mechanical thrombectomy and successful postoperative recanalization in the Stroke Center of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2019 to May 2020 were retrospectively enrolled. According to the number of retrieval attempts during the procedure, the patients were divided into <3-attempt group and ≥3-attempt group. The demographic data, procedure-related indexes, periprocedural complications and outcomes at 90 d after the procedure were compared between the two groups.Results:A total of 106 patients, aged 69.8±1.3 years, were enrolled, and 55 were males (51.9%). Eight-three patients (78.3%) were in the <3-attempt group, and 23 (21.7%) were in the ≥3-attempt group. Forty-one patients (38.7%) had good outcomes (the modified Rankin Scale score ≤2) at 90 d, and 11 (10.4%) died. There were no significant differences in the incidence of intracranial hemorrhage (30.4% vs. 20.5%; χ2=1.019, P=0.313), the good outcome rate at 90 d (34.8% vs. 39.8%; χ2=0.188, P=0.665) and mortality (8.7% vs. 10.8%; P=0.999) between the ≥3-attempt group and <3-attempt group, but the incidence of symptomatic intracranial hemorrhage was significantly higher than that in the <3-attampt group (13.0% vs. 1.2%; P=0.031). Multivariate logistic regression analysis showed that the number of retrieval attempts was not significantly associated with poor outcome. Conclusion:The more retrieval attempts may be related to symptomatic intracranial hemorrhage, but it does not affect the clinical outcomes of patients with successful recanalization at 3 months.
3.Analysis of the association between ATP-binding cassette transporter family and the efficacy of immunotherapy for bladder cancer
Tingzheng WANG ; Qing ZHANG ; Hongqian GUO
Journal of Modern Urology 2024;29(12):1033-1038
[Objective] To investigate the clinical utility of ATP-binding cassette transporter family in immunotherapy for bladder cancer based on IMvigor210 and UNC-108 (GSE176307) datasets. [Methods] Gene expression data of 348 patients with bladder urothelial carcinoma were downloaded from the IMvigor210 database.Firstly, consensus clustering was performed to the gene expression levels of the ATP-binding cassette transporter family, resulting in two clusters: Cluster 1 and Cluster 2.Survival analysis was conducted between the two clusters.Next, univariate Cox regression was employed to identify ATP-binding cassette transporter family genes significantly affecting prognosis.A predictive model was constructed using the random survival forest algorithm to predict treatment response and survival outcomes in patients with bladder cancer receiving immunotherapy.The model's accuracy was validated with UNC-108 dataset.Then, ESTIMATE and ssGSEA were applied to analyze differences in the tumor microenvironment.Furthermore, oncoPredict algorithm was used to predict the sensitivity of patients to cisplatin. [Results] A total of 9 ATP-binding cassette transporter family genes were selected to construct the ABC score predictive model.In the IMvigor210 datasets, the Kaplan-Meier analysis revealed that patients with low ABC score had significantly longer overall survival compared to those with high ABC score (P<0.001). The ABC score model demonstrated good performance with area under the ROC curve (AUC) of 0.80, 0.87, and 0.88 for predicting 0.5-year, 1-year, and 1.5-year survival, respectively.The predictive ability of the ABC score for immunotherapy response, with an AUC of 0.78, outperformed that of TMB (AUC: 0.72) and PD-L1 (AUC: 0.58). The ABC score also exhibited favorable predictive performance in the UNC-108 validation cohort.ABC score was also significantly correlated with tumor microenvironment immune scores, various immune cells, and the expression of immune checkpoint genes. [Conclusion] ATP-binding cassette transporter family is closely associated with the tumor microenvironment and the efficacy of immunotherapy for bladder cancer, making it a potential novel biomarker for immunotherapy.