Objective To investigate the effect of estrogen on the expression of matrix metallopro-teinase protein 9 and 2(MMP-9,MMP-2)and tight junction protein Occludin in mouse brain mi-crovascular endothelium cell line bEnd.3 injured by homocysteine(Hcy),and explore the protec-tive effects and underlying mechanisms of estrogen on small cerebral vascular diseases.Methods bEnd.3 cells were treated with Hcy andβ-estradiol respectively,and the optimal concentration was determined for cell proliferation and toxicity with enhanced cell counting kit-8.The cells were divided into control group,Hcy group(200 μmol/L),E2β group(200 nmol/L)and combined treatment group(200 nmol/L E2β treatment for 30 min followed by 200 μmol/L Hcy).After 6 h corresponding treatment,Western blotting was used to detect the protein levels of MMP-9,MMP-2 and Occludin in each group of cells.Results There were no significant differences in the protein levels of MMP-9,MMP-2 and Occludin in above groups after treatment for 24 and 48 h(P＞0.05).Compared with the control group,the expression levels of MMP-9 and MMP-2 was signifi-cantly increased in the Hcy Group after treatment of 72 h(1.45±0.14 vs 1.00±0.00,1.35±0.15 vs 1.00±0.00,P＜0.05),while the level of Occludin was obviously decreased(0.64±0.05 vs 1.00±0.00,P＜0.05).Compared in the Hcy Group,the MMP-9 and MMP-2 levels were obviously decreased(0.84±0.19 vs 1.45±0.14,1.01±0.78 vs 1.35±0.15,P＜0.05),and that of Occludin was notably elevated in the combined treatment group(0.91±0.10 vs 0.64±0.05,P＜0.05).Con-clusion E2β can ameliorate blood-brain barrier damage in Hcy-treated bEnd.3 cells,resulting in decreased MMP-9 and MMP-2 expressions and increased Occludin expression.

Objective:To investigate the correlation between serum anti-phospholipase A2 receptor antibody (SAb) combined with glomerular complement C3 (GC3) deposition and clinicopathologic features and prognosis in patients with idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The patients diagnosed with IMN in Affiliated Hospital of Qingdao University from July 1, 2019 to April 30, 2022 were enrolled, and the clinical and pathological data were collected and analyzed. The patients were divided into negative SAb and negative GC3 (SAb -/GC3 -) group, negative SAb and positive GC3 (SAb -/GC3 +) group, positive SAb and negative GC3 (SAb +/GC3 -) group and positive SAb and positive GC3 (SAb +/GC3 +) group according to the status of SAb titer and GC3 deposition. Clinical and pathological characteristics among the groups were compared. Kaplan-Meier survival curve was used to compare the cumulative renal remission rates of different groups. Cox regression analysis model was used to analyze the related factors of renal remission. Results:A total of 143 IMN patients aged (53.35±12.34) years old were included in the study, including 94 males (65.7%). There were 17 patients (11.9%) in the SAb -/GC3 - group, 30 patients (21.0%) in the SAb -/GC3 + group, 19 patients (13.3%) in the SAb +/GC3 - group, and 77 patients (53.8%) in the SAb +/GC3 + group. Compared with SAb -/GC3 - group, the level of serum albumin was lower in the SAb +/GC3 + group, and the level of 24 h urine protein, SAb titer, and the proportions of glomerular anti-phospholipase A2 receptor antigen and renal tubule atrophy were higher in the SAb +/GC3 + group (all P<0.05). After 26.0 (19.0, 36.0) months of follow-up, a total of 96 patients (67.1%) attained remission. The proportion of patients receiving immunosuppressive therapy in the SAb +/GC3 + group was higher than that in the SAb -/GC3 - group [93.5% (72/77) vs. 70.6% (12/17), fisher value=8.974, P=0.016] and the proportion of renal remission rate in the SAb +/GC3 + group was lower than that in the SAb -/GC3 - group [49.4% (38/77) vs. 100% (17/17), χ2=25.438, P<0.001]. Kaplan-Meier survival curve result showed that the cumulative renal remission rate in the SAb +/GC3 + group was significantly lower than that in the SAb -/GC3 - group (Log-rank χ2=31.538, P<0.01). Multivariate Cox regression analysis result showed that 24 h urine protein level ( HR=0.891, 95% CI 0.803-0.988, P=0.029), SAb titer ( HR=0.996, 95% CI 0.992-1.000, P=0.042) and SAb +/GC3 + (with SAb -/GC3 - group as reference, HR=0.414, 95% CI 0.204-0.827, P=0.013) were independent related factors for renal remission in patients with IMN. Conclusions:IMN patients with positive SAb and GC3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rates, and are more likely to have poor prognosis. The combined assessment of SAb and GC3 deposition may be helpful for evaluating prognosis and guiding treatment in IMN patients.