1.Effect of Autophagic Flux Impairment-mediated Apoptosis on Pressure Overload-induced Heart Failure
Shuangxiu LI ; Qi ZHENG ; Gaosheng YIN ; Ping YANG ; Lu LING
Journal of Kunming Medical University 2025;46(9):54-62
Objective To explore the effect of autophagy and apoptosis on heart failure(HF)induced by pressure overload.Methods In the animal experiment,twenty C57/BL6J mice(aged 8-12 weeks)underwent transverse aortic constriction(TAC)to duplicate the model of pressure overload-induced HF.The mice were randomly divided into sham group(only threading was performed without ligation)and surgery group(TAC group).Four weeks after post-operation,echocardiography was used to assess cardiac function.Ratios of heart weight/body weight(HW/BW)and heart weight/tibia length(HW/TL)were calculated.Histopathological changes were assessed with Masson and WGA staining.Quantitative real-time PCR was used to quantify the mRNA levels of hypertrophy-related genes:ANP,BNP,and β-MHC.Western blot analysis was used to determine the expression of autophagy proteins(Beclin1,P62,LC3-Ⅱ/Ⅰ)and apoptosis proteins(BCL2,BAX,c-caspase-3).In the cell experiment,H9C2 cells were induced with angiotensin Ⅱ(Ang Ⅱ)to serve as an in vitro HF model.The H9C2 cells were divided into control(PBS group),Ang II group,PBS with chloroquine(PBS+CQ group),and Ang Ⅱ with chloroquine(Ang II+CQ group).After modeling,western blotting was used to assay apoptosis protein expression(Beclin1,P62,LC3-Ⅱ/Ⅰ,BAX,BCL2,c-caspase-3).Autophagy double-labeled lentivirus mRFP-eGFP-LC3 was used to detect autophagic flux.Results Compared with the control group,the TAC group enlarged mouse heart,significantly increased HW/BW and HW/TL values,and decreased ejection fraction(EF)and shortened fraction(FS)(P<0.001).Fibrosis and collagen deposition were aggravated,the cross-sectional area of cardiomyocytes increased(P<0.001),and the mRNA expression levels of myocardial hypertrophy markers ANP,BNP and β-MHC(P<0.001)were significantly increased,suggesting the successful construction of an understress-induced heart failure model in vivo.Compared to the control group,there was an upregulation of autophagy-related proteins Beclin1,P62,LC3-II/I(P<0.01)and apoptosis proteins BAX,c-caspase-3(P<0.01),while the expression of BCL-2(P<0.001)protein was reduced.In the cell experiments,in the in vitro heart failure model group,the autophagosomes were significantly increased,but there was no significant change in autophagic lysosomes,and autophagic flux was impaired.After blocking the autophagy process with chloroquine(CQ),the Ang II+CQ group showed further increased expression of the autophagic proteins Beclin 1,LC3-II/I,P62(P<0.05),and apoptosis proteins BAX and cleaved caspase-3(P<0.01)compared to the Ang II group,and a further decrease in protein levels of BCL-2(P<0.001).Additionally,CQ led to a significant increase in the number of autophagosomes,but there was no significant change in autophagic lysosomes,and autophagic flux was impaired.Conclusion Both autophagy and apoptosis are activated in pressure overload-induced heart failure,and impaired autophagic flux exacerbates apoptosis in this model.
2.The value of biparametric MRI in the detection of prostate cancer
Yueyue ZHANG ; Wenlu ZHAO ; Chaogang WEI ; Tong CHEN ; Mengjuan LI ; Shuo YANG ; Shuangxiu TAN ; Beibei HU ; Qi MA ; Yongsheng ZHANG ; Boxin XUE ; Junkang SHEN
Chinese Journal of Radiology 2019;53(2):109-114
Objective To explore the difference in efficacy between multiparametric MRI (Mp-MRI) based on prostate imaging reporting and data system version 2 (PI-RADS v2) and abbreviated biparametric MRI (Bp-MRI) in detecting prostate cancer (PCa) and clinically significant prostate cancer (csPCa), and to evaluate the consistency of image interpretation between different readers. Methods The imaging, pathological and clinical data of patients with prostatic Mp-MRI in our hospital from February 2015 to June 2018 were retrospectively analyzed. At the beginning, 250 patients were randomly selected. Two radiologists visually evaluated the images of those patients using two 5-point scoring schemes based on Mp-MRI and Bp-MRI. The remaining cases were independently proceeded by one of the radiologists using two schemes respectively. Weighted Kappa test was used to assess the consistency of the results interpreted by the two radiologists. The receiver operating characteristic (ROC) curve was used to evaluate the efficiency of the two scoring schemes in detecting PCa and csPCa, and with Z test to investigate whether there was any difference in detection efficiency between the two schemes. Results Nine hundred and seventy eight patients were eventually enrolled in the study. The results of the consistency assessment showed that there was good agreement between the two radiologists, whether using Mp-MRI or Bp-MRI, with the weighted Kappa coefficient of 0.800 and 0.812, respectively. The ROC curve analysis showed that the area under the curve (AUC) of PCa detected by Mp-MRI and Bp-MRI was 0.873 and 0.879, respectively, and the AUC of csPCa detected was 0.922 and 0.932, respectively. In addition, there was no statistically significant difference between the AUC of PCa and csPCa detected by the two schemes (P>0.05). Conclusion The Bp-MRI scoring scheme has good stability in the evaluation of benign and malignant prostate, and its detection efficiency of PCa or csPCa is not lower than that of standard Mp-MRI based on PI-RADS v2.

Result Analysis
Print
Save
E-mail