Objective To explore the evaluation value of three-dimensional echocardiographic parameters for left ventricular reverse remodeling(LVRR)after transcatheter aortic valve replacement(TAVR)in patients with severe bicuspid aortic valve(BAV)stenosis.Methods A total of 140 pa-tients with severe BAV stenosis admitted to our hospital from January 2021 to April 2024 were select-ed.All patients underwent TAVR surgery and completed three-dimensional echocardiographic exami-nations.According to whether LVRR occurred,the patients were divided into occurrence group(69 cases)and non-occurrence group(71 cases).Clinical data and three-dimensional echocardiographic parameters[left ventricular remodeling index(LVRI),left ventricular mass index(LVMI),left ventricu-lar end-diastolic volume index(LVEDVI),and left ventricular end-systolic volume index(LVESVI)]were compared between the two groups.Logistic regression analysis was used to analyze the risk factors for LVRR after TAVR in patients with severe BAV stenosis.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of three-dimensional echocardiographic parameters for LVRR after TAVR in patients with severe BAV stenosis.Results Among the 140 patients with severe BAV stenosis after TAVR,69 cases developed LVRR,with an incidence rate of 49.29％.Compared with the non-occurrence group,the occurrence group had lower values of LVMI,LVEDVI,and LVESVI,and the differences were statistically significant(P＜0.05).The proportion of patients with cardiac function classification ≥ grade Ⅲ and the calcification score in the occurrence group were lower than those in the non-occurrence group,and the differences were statistically significant(P＜0.05).Logistic regression analysis results showed that cardiac function classification＜grade Ⅲ,low values of LVMI,LVEDVI,LVESVI,and LVRI were protective fac-tors for LVRR after TAVR in patients with severe BAV stenosis.ROC curves showed that the areas under the curve(AUCs)and 95％CI of LVRI,LVMI,LVEDVI,and LVESVI for predicting LVRR after TAVR alone were 0.876(0.810 to 0.926),0.878(0.812 to 0.927),0.758(0.678 to 0.826),and 0.786(0.709 to 0.851),respectively.The AUCs(95％CI)of the combined model and the predictive model were 0.911(0.852 to 0.953)and 0.947(0.895 to 0.978),respective-ly,indicating high efficacy of both models.Conclusion After TAVR,LVRI,LVMI,LVEDVI,and LVESVI are closely related to LVRR in patients with severe BAV stenosis and are influencing factors for LVRR occurrence in these patients.The combined detection of these indicators has a high predictive value for LVRR after surgery.

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.