Objective:To investigate the effect and mechanism of astragaloside IV (AS-IV) combined with glucocorticoids in the treatment of puromycin aminonucleoside (PAN) rat nephropathy model.Methods:Forty specific pathogen-free healthy male Wistar rats (150-180 g) were randomly divided into 5 groups: control group, PAN group, AS-IV treatment group (PAN+AS-IV group), methylprednisone (MP) treatment group (PAN+MP group), and AS-IV+MP treatment group (PAN+AS-IV+MP group). The model was established by a single tail vein injection of PAN (50 mg/kg body weight). The treatment groups were given 40 mg·kg -1·d -1 AS-IV by intragastric administration and 15 mg·kg -1·d -1 MP by intraperitoneal injection for 10 consecutive days at the same time of modeling. Urine sample was collected on the 11th day of the experiment. The urine protein, urine creatinine and blood albumin were detected by biochemical analyzer. The changes of nephrin and synaptopodin in renal tissues were detected by immunofluorescence assay, and the expressions of nephrin, RhoA and Rac/Cdc42 proteins were detected by Western blotting. Results:Compared with the control group, urine protein creatinine ratio (uPCR) was significantly increased, serum albumin (Alb) was significantly decreased in the PAN group, nephrin expression was significantly down-regulated, and the expressions of RhoA and Rac/Cdc42 were significantly up-regulated in the renal tissue of the PAN group (all P<0.01). Compared with PAN group, serum Alb levels in PAN+AS-IV group and PAN+AS-IV+MP group were significantly increased (both P<0.01), and the uPCR levels in PAN+MP group ( P<0.05) and PAN+AS-IV+MP group ( P<0.01) were significantly decreased (all P<0.05). Compared with the PAN group, the relative expressions of nephrin in renal tissue of all drug intervention group (PAN+AS-IV group, PAN+MP group and PAN+AS-IV+MP group) were significantly increased, while the relative expressions of RhoA and Rac/Cdc42 were significantly decreased (all P<0.01). The immunofluorescence results suggested that the expressions of nephrin and synaptopodin in renal tissue of PAN group were significantly down-regulated compared with the control group, which were reversed in all treatment groups, and the reversion was most pronounced in the PAN+AS-IV+MP group. Conclusion:Both AS-IV and glucocorticoid can improve PAN-induced podocyte injury, and the combination of the two has synergistic action, which may be related to inhibiting the activation of Rho family signaling pathway.

OBJECTIVE: To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients. METHODS: A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment. RESULTS: Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05). CONCLUSION Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.
Humans ; Autoantibodies ; Cyclosporine/therapeutic use* ; Glomerulonephritis, Membranous/diagnosis* ; Homozygote ; Immunosuppressive Agents/therapeutic use* ; Pharmacogenomic Testing ; Receptors, Phospholipase A2 ; Sequence Deletion ; Serum Albumin ; Tacrolimus/therapeutic use*

Trauma is the leading cause of death for people under 40 years old in the world. At present, the rescue and treatment system of trauma patients in China is not yet well established, and the mortality of trauma patients is higher than those in the developed countries. Improving the treatment system is the key to reducing the trauma mortality. In order to innovate the service mode of trauma first aid, further promote the establishment of regional trauma first aid system, improve the ability of trauma treatment, reduce the mortality and disability rate of trauma patients in Jiangxi Province, recently Health Commission of Jiangxi Province and the First Affiliated Hospital of Nanchang University have reached a consensus on the establishment of Jiangxi trauma first aid center. In order to provide reference for the construction of trauma treatment system, the author analyzes the following aspects including functional positioning, basic requirements, organization management, and evaluation of core indicators.