Background The M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) is a common immune-related disease in adults. Vascular endothelial growth factor A (VEGFA) is the key mediator of angiogenesis, which leads to numerous kidney diseases. However, the role of VEGFA in IMN is poorly understood. Methods In the present study, we downloaded the microarray data GSE115857 from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified with R software. The cytoHubba plug-in were used to identify hub genes from the protein–protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signalling pathway in IMN. CCK8 was performed to assess the cell viability in human vascular endothelial cells (HVECs). Then, passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Animals treated with VEGFA inhibitor bevacizumab (BV), with saline as a positive control. Proteinuria was evaluated by biochemical measurements. Immunohistochemistry and immunofluorescence was used to evaluate relative proteins expression. Electron microscopy was performed to observe the thickness of the glomerular basement membrane (GBM). Results We revealed 3 hub genes, including one up-regulated gene VEGFA and two down-regulated genes JUN and FOS, which are closely related to the development of PLA2R-associated IMN. Pathway enrichment analysis found that the biological process induced by VEGFA is associated with PI3K/Akt signalling. GSEA showed that the signalling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. We confirmed the high expression of VEGFA, PI3K, and AKT in IMN renal biopsy samples with immunohistochemistry. In HVECs, we found that BV suppresses cell viability in a time and dose dependent manner. In vivo , we found low dose of BV attenuates proteinuria via inhibiting VEGFA/PI3K/AKT signalling. Meanwhile, low dose of BV alleviates the thickening of the GBM. Conclusion VEGFA/PI3K/AKT signalling may play significant roles in the pathogenesis of IMN, which may provide new targets for the treatment of IMN. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-022-02936-y.
Objective To investigate the effects of different filtration fractions (FFs) during daytime continuous venovenous hemodiafiltration (CVVHDF) post-dilution. Methods From April to December 2021, forty patients who received CVVHDF in the Second Affiliated Hospital of Nanchang University were randomly assigned to the low FF group (FF: 20–25%) or the high FF group (FF: 25–30%) and then compared with each other. The lifespan of the extracorporeal circuit and other performance metrics were compared between the two groups. Results During treatment, there was no statistically significant difference in arterial pressure between the two groups at 2 hours, 6 hours and the end of treatment compared with that at 1 hour of treatment (P = 0.30, 0.27, 0.87). There was no statistically significant difference between the venous pressure at 2 hours, 6 hours and the end of treatment compared with that at 1 hour of treatment (P = 0.55, 0.53, 0.53), and there was also no statistically significant difference in transmembrane pressure (P = 0.55, 0.63, 0.53). There was no statistically significant difference in the clotted filter or the extracorporeal circulation circuit at the end of CRRT between the two groups (P = 0.95, 0.31). There were statistically significant differences in the clearance efficiency of serum creatinine (P = 0.04). Conclusion For patients with daytime CRRT, CVVHDF treatment with FFs < 25% compared with FFs of 25–30% has no statistically significant difference in the risk of coagulation during cardiopulmonary bypass, while the efficacy seems to be significantly different. This study aims to provide supportive data for the criteria for defining FF in clinical practice.
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