Objective To observe the clinical efficacy of beraprost sodium on early stage of diabetic nephropathy(DN).Methods We measured serum levels of serum soluble intercelluhar adhesion molecule (sICAM)-1 in 27 cases with diabetes without nephropathy and 48 cases with early DN.Patients with early DN were randomly assigned into two treatment groups:the conventional treatment group and the beraprost sodium treatment group.Changes of sICAM-1 and C-reactive protein (CRP) levels and urinary albumin excretion rate (UAER) were measured in the two groups before and after treatment.Results The serum sICAM-1 levels in early DN patients was significantly higher than that of the diabetes without nephropathy group((1385 ± 171) g/ Lvs.(943 ± 167) g/L;t =1.034,P =0.002).There were no significant difference observed on levels of sICAM-1,CRP and UAER between the two treatment groups (P ＞ 0.05).The level of sICAM-1 and CRP in the beraprost sodium treatment group was significantly lower than those before treatment (P ＜ 0.05 or P ＜ 0.01).The symptoms were significantly alleviated in both groups (P ＜ 0.05 or P ＜ 0.01),especially for the beraprost sodium treatment group(P ＜ 0.05 or P ＜ 0.01).Conclusion Patients with early DN have elevated serum sICAM-1 levels.Treatment of beraprost sodium has protective effect on early DN as it significantly decreases the serum levels of sICAM-1 and CRP in patients with early DN.

Objective To investigate the single nucleotide polymorphism at G-395A site of the Klotho (KL) gene and to analyze its correlation with the coronary heart disease(CHD) and serum Cystatin C(Cys C) level in the elderly Chinese Han population in central China.Methods A case-control study was conducted in 278 elderly Chinese Han population in this department,who were divided into CHD group(138 cases)and control group(140 cases) according to bear angiography coronary or not.G-395A polymorphism of KL gene was determined by TaqMan Gene probe method,and the relationship between G-395A polymorphism and coronary heart disease and serum Cys-C level was analyzed.Results Compared with the control group,the frequency of GG genotype of G-395A in CHD group was significantly higher,and the frequency of AA genotype and AG genotype was not statistically significant.The levels of Cys-C in the GG genotype were higher than those in the AA and AG genotypes both in the control group and coronary heart disease group.Conclusion In the elderly Han population in central China,the risk of suffering coronary heart disease is higher among the GG genotype of the G-395A locus of the KL gene.KL gene G-395A site gene mutation may affect the development of atherosclerosis by affecting blood Cys-C levels.

On May 7, 2020, the International Pediatric Nephrology Association released the clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome.The recommendations suggested new diagnostic definitions to guide treatment.In addition, more practical suggestions on diagnostic procedures of steroid-resistant nephrotic syndrome, indications, contraindications and protocols for non-immunosuppressive and immunosuppressive therapies, and management of complications and end-stage kidney diseases were proposed.The main points of the recommendations are introduced in this article.

Objective:To investigate the expression of inositol 1, 4, 5-triphate receptor (IP 3R)-glucose-regulated protein 75 (Grp75)-voltage dependent anion channel 1 (VDAC1)-mitochondrial Calcium uniporter (MCU) Calcium axis molecules in proteinuria and to explore its upstream regulator. Methods:Sixteen Sprague Dawley rats were divided into control group (6 rats) and Adriamycin (ADR) group (10 rats). Nephropathy rat model was established by single injection of ADR through tail vein.The glomerular expression of IP 3R, Grp75, VDAC1, MCU and the activation marker of mammalian target of Rapamycin complex 1 (mTORC1) were analyzed by immunohistochemical staining.In cultured mouse podocyte, ADR was used to induce podocyte injury, and the Everolimus of different concentrations was applied for intervention.The expression of the Calcium axis molecules and apoptosis marker was analyzed. Results:Compared with control group, the glomerular expression of IP 3R (0.02±0 vs.0, P<0.001), Grp75 (0.04±0 vs.0, P<0.001), VDAC1 (0.04±0 vs.0.01±0, P<0.001), and MCU (0.05±0.01 vs.0.01±0, P<0.001) were significantly increased in ADR-induced nephropathy rats, and the activation marker of mTORC1 (0.57±0.01 vs.0.18±0, P<0.001) was increased as well.In cultured mouse podocytes, compared with control group, the expression of Grp75 (1.89±1.17 vs.0.16±0.08, P=0.001), VDAC1 (1.59±0.34 vs.0.20±0.07, P=0.006), and MCU (1.56±0.38 vs.0.46±0.35, P=0.014) were obviously increased in ADR induced podocytes, and the activation marker of mTORC1 (2.12±0.08 vs.0.39±0.09, P<0.001) was also increased.Compared with the ADR induced podocytes, the expression of Grp75 (0.26±0.20 vs.1.89±1.17, P=0.001), VDAC1 (0.40±0.26 vs.1.59±0.34, P=0.014) and MCU (0.60±0.32 vs.1.56±0.38, P=0.029) in podocytes treated with ADR and 1.0 nmol/L Everolimus were remarkably decreased, accompanied with the decrease of mitochondrial calcium [(2 664.00±140.57) U vs.(3 025.16±180.92) U, P=0.023] and apoptosis marker cleaved Caspase-3 (0.55±0.28 vs.1.48±0.45, P=0.011). Conclusions:The over-production of IP 3R-Grp75-VDAC1-MCU Calcium axis molecules accompanied with the hyper-activation of mTORC1 was involved in ADR induced nephropathy rats.mTORC1 inhibitor decreased the expression of Calcium axis molecules in mouse podocytes, which might involve in the mechanism of mTORC1 inhibitor′s effects on podocyte.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.