OBJECTIVE:To investigate the impact of renin-angiotensin-aldosterone-system (RAAS) inhibitors on complement component 4 (C4) serum levels in patients with immunoglobulin A nephropathy (IgAN).METHODS:A total of 423 patients diagnosed with IgAN at Shanxi Provincial People's Hospital, China, between 1 January 2017 and 31 December 2021 were divided into two groups, a RAAS inhibitor group and a non-RAAS inhibitor group, for comparative analysis.RESULTS:The RAAS inhibitor group exhibited significantly increased C4 and eGFR levels and had a higher proportion of patients with hypertension compared with the non-RAAS inhibitor group. Serum C4 levels were positively correlated with 24-hour urine protein, serum C3 levels and blood uric acid levels but negatively correlated with eGFR levels. In addition, serum C4 levels were positively correlated with the severity of mesangial hypercellularity and interstitial/tubular injury. Through prognostic analysis, serum C4 was identified as an independent risk factor for the progression of IgAN.CONCLUSION:Renin-angiotensin-aldosterone-system inhibitors can increase serum C4 levels in patients with IgAN and may represent an independent risk factor for disease progression.

ObjectiveTo investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy (IMN).MethodsA total of 77 patients with IMN diagnosed in both our hospital and other hospitals were included in this study; the patients were divided into two groups: a treatment-naïve group (n = 19) and a refractory/relapsed group (n = 58). The clinical data of the patients, including urine examination, blood test, safety evaluation and efficacy evaluation results, were analysed retrospectively. The changes in clinical biochemical indexes and adverse reactions were compared between the two groups before and after treatment, and the clinical efficacy of rituximab (RTX) in the treatment of primary IMN and refractory recurrent membranous nephropathy was evaluated.ResultsOf the 77 patients included in this study, the average age was 48 years, and there was a male-to-female ratio of 61:16. There were 19 cases in the initial treatment group and 58 cases in the refractory/relapse group. The 24-hour urine protein quantification, cholesterol, B cell count and M-type phospholipase A2 receptor (PLA2R) results in the 77 patients with IMN after treatment were all lower than those before treatment, and the differences were statistically significant (P < 0.05). Serum albumin was higher than before treatment, and the difference was statistically significant (P < 0.05). The total remission rate in the initial and refractory/relapsed treatment groups was 84.21% and 82.76%, respectively. There was no statistical difference in the total remission rate between the two groups (P > 0.05). During treatment, nine patients (11.69%) experienced infusion-related adverse reactions, which were relieved rapidly after symptomatic treatment. The anti-PLA2R antibody titre of the refractory/relapsed group was significantly negatively correlated with serum creatinine (r = −0.187, P = 0.045) and significantly correlated with 24-hour urine protein (r = −0.490, P < 0.001). There was a positive correlation and a significant negative correlation with serum albumin (r = −0.558, P < 0.001).ConclusionsRegardless of whether RTX is used as an initial therapy or refractory/relapsed membranous nephropathy, most patients with IMN have complete or partial remission after RTX treatment, with mild adverse reactions.

OBJECTIVE:In this study, we used network pharmacology to explore the possible therapeutic mechanism underlying the treatment of diabetic nephropathy with Yishen capsules.METHODS:The active chemical constituents of Yishen capsules were acquired using the Traditional Chinese Medicine Systems Pharmacology platform and the Encyclopedia of Traditional Chinese Medicine. Component target proteins were then searched and screened in the BATMAN database. Target proteins were cross-validated using the Comparative Toxicogenomics Database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target proteins were performed. Then, protein-protein interaction (PPI) analysis was performed using the STRING database. Finally, a pharmacological network was constructed to show the component-target-pathway relationships. Molecular docking was used to analyse the interaction between drug components and target proteins.RESULTS:In total, 285 active chemical components were found, including 85 intersection targets against DN. In the pharmacological network, 5 key herbs (A. membranaceus, A. sinensis, E. ferox, A. orientale, and R. rosea) and their corresponding 12 key components (beta-sitosterol, beta-carotene, stigmasterol, alisol B, mairin, quercetin, caffeic acid, 1-monolinolein, kaempferol, jaranol, formononetin, and calycosin) were screened. Furthermore, the 12 key components were related to 24 target protein nodes (e.g., AGT, AKT1, AKT2, BCL2, NFKB1, and SIRT1) and enriched in 24 pathway nodes (such as the NF-kappa B, AGE-RAGE, toll-like receptor, and relaxin signaling pathways). Molecular docking revealed that hydrogen bond was formed between drug components and target proteins.CONCLUSION:In conclusion, the active constituents of Yishen capsules modulate targets or signaling pathways in DN pathogenesis.

1例55岁女性患者因"反复高钾血症2年,全身抽搐1 d"入院.患者2年前诊断为慢性肾脏病,近2年多次出现恶心、呕吐及双足、双小腿麻木不适等症状,血钾水平波动于4.50～7.14 mmol/L.入院前1天出现全身抽搐,血肌酐715.71μmol/L,血钾6.18 mmol/L.入院时血钾6.64 mmol/L、血肌酐690.51μmol/L、空腹血糖8.6 mmol/L.完善检查后诊断为慢性肾脏病,高钾血症,糖尿病肾病,2型糖尿病,糖尿病视网膜病变,高血压.予静脉注射葡萄糖+胰岛素、呋塞米、碳酸氢钠,口服环硅酸锆钠散等对症治疗.患者住院期间血钾水平维持在正常范围内.出院后随访1年,患者未再出现高钾血症.

Refractory peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) caused by Burkholderia cepacia is very rare. Herein, we describe a case of B. cepacia-related refractory peritonitis and present a literature review of similar cases. A 62-year-old male patient presented with diffuse abdominal pain, bloating, and turbid peritoneal effluent. Initial dialysis effluent culture was negative for any microorganism. The patient initially underwent treatment with piperacillin-sulbactam. The second dialysis effluent culture was positive for gram stain and later tested positive for B. cepacia. Peritoneal dialysis (PD) catheter removal was recommended, and the patient agreed to undergo regular hemodialysis. To the best of our knowledge, this is the first case of B. cepacia-related refractory peritonitis in a patient undergoing CAPD with no history of a recent hospitalization. B. cepacia infections can result in death in some areas. Therefore, timely catheter removal and switching treatment to hemodialysis is recommended for patients with B. cepacia-related refractory peritonitis.

Objective:To understand the laboratory characteristics for the diagnosis of immunoglobulin G4-related disease (IgG4-RD).Methods:The clinical data of 28 patients with IgG4-RD and renal damage (IgG4-RKD) diagnosed in our hospital from January 2017 to May 2019 were retrospectively analyzed. The correlation between serum IgG4 concentration and clinical features as well laboratory test results was analyzed. The 28 patients were divided into two groups: high serum IgG4 concentration group and normal serum IgG4 concentration group. The serum creatinine value, erythrocyte sedimentation rate, IgG concentration, IgA concentration, complement C3, C4 concentration, peripheral blood eosinophils, hemoglobin, IgG4/IgG and other related parameters were compared between the two groups. SPSS 20.0 statistical software was used for analysis. The two groups of measurement parameters were compared between groups by independent sample t test, non-normal measurement parameters were compared between groups by Mann-Whitney U test analysis, and the correlation between patients' IgG4 and each detection parameter was analyzed by Spearman correlation analysis. Results:Among the 28 patients, 17 were male and 11 were female, with an average age of (62±14) years. The serum IgG4 concentration increased in 75% of the patients ( n=21), with an average value of 3.01(1.41, 7.52) g/L, the serum IgG concentration increased in 64.3% of patients ( n=18), with an average value of 18.91 (12.88, 24.88) g/L, and the complement C3 decreased in 50% of the patients ( n=14), with an average value of(0.77±0.28) g/L. IgG4 was positively correlated with IgG ( r=0.422, P=0.025), IgG4/IgG ( r=0.951, P<0.01), ESR ( r=0.543, P<0.01) and peripheral blood eosinophils ( r=0.487, P<0.01), but negatively correlated with complement C3 ( r=-0.431, P=0.022) and C4 ( r=-0.504, P<0.01) levels. There were significant differences in IgG ( Z=-2.255, P=0.023), IgG4/IgG ( Z=-3.793, P<0.01), C3 ( t=7.380, P<0.01) and ESR ( t=-2.195, P=0.037) between the elevated IgG4 group and the normal group. Conclusion:Serological characteristics of IgG4-RKD combined with clinical manifestations may be able to diagnose IgG4-RKD in early stage.

Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER) stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

OBJECTIVES:An animal model using beagle dog has been established to investigate the postmortem redistribution of lidocaine.MATERIALS AND METHODS:18 dogs were euthanized and injected lidocaine (13 mg/kg) via epidural immediately. An autopsy was performed at 0, 12, 24, 48, 72, 96 hours after drug administration. All animals were stored in supine position at room temperature. For the other groups, lidocaine was given via epidural 6, 12, 24 hours after dogs were euthanized. Followed treatments were as above described. All samples were treated for detection of the concentration of lidocaine.RESULTS:It was found that lidocaine could diffuse via blood vessel rapidly post administration. And the concentration of lidocaine in the blood from ventriculus sinister increased obviously in a time-dependent manner. Meanwhile, the postmortem tissue distribution of lidocaine was significantly different. However, the process of postmortem redistribution of lidocaine was obviously delayed in dogs which were given drugs after death.CONCLUSIONS:Together results revealed the process of postmortem redistribution of lidocaine via epidural injection, and provided the method to distinguish the lidocaine-induced death and drug administration after death.

大鼠阿霉素肾病(adriamycin-induced nephropathy.AND)是通过阿霉素及其代谢产物诱发肾小球上皮细胞脂质过氧化,破坏肾小球滤过膜结构和功能,最终导致滤过屏障的通透性而引起蛋白尿[1].近年来研究证实Podocin是与足细胞裂孔隔膜(slit diaphragm,SD)结构功能相关的重要蛋白分子,对维持正常肾小球功能发挥着重要作用.除了裂孔隔膜之外肾小球基膜(glomerulus basement membrane.GBM)也是选择性滤过的主要屏障.层黏连蛋白(laminin,LN)是基膜(basement membrane,BM)的主要成分,参与基膜的构建及细胞黏附、增殖和分化,对肾脏的正常发育至关重要.

Objective To assess the efficacy of different sequential therapy regimens according to the theory of cell cycle on adriamycin-induced nephropathy (AIN) rats. Methods SD rats were randomly divided into five groups:control group (n=8),AIN model group (n=8),MP+ CsA+MMF group (n=8),MP+CsA+CTX treated group (n=8) and MP+FK506+Rapa group (n=8).The levels of 24-hour urinary protein,serum total protein (TP),albumin (Alb),cholesterin (Chol),triglyeride (TG),serum urea nitrogen (BUN),serum creatinine (Scr) were measured.The renal pathological changes were observed by light microscope.The expressions of nephrin and podocin were analyzed by immunohistochemistry and real-time PCR.The expression of CTGF was detected by Western blotting. Results (1)Compared with control group,the levels of 24-hour urinary protein in AIN model group were obviously increased at 2nd,4th,8th and 12th week (all P＜0.01).The level of 24-hour urinary protein were obviously decreased in treatment groups at 8th and 12th week than those in AIN model group (all P＜0.05). (2)The levels of TP and Alb were significantly lower in AIN model group than those in control group (all P＜0.01),and the levels of TG and Chol were significantly higher in AIN model group than that in control group (all P＜0.01).The levels of TP and Alb were significantly higher and the levels of TG and Chol were significantly lower in treatment groups than those in AIN model group (all P ＜0.05). (3)The results of immunohistochemistry indicated the expressions of nephrin and podocin in treatment group rats were obviously higher than those in AIN model group (all P＜0.01). (4)The results of Western blotting indicated the expression of CTGF in treatment group rats was higher than that in AIN model group (P＜0.05).The effect of inhibitting fibrous degeneration in MP +FK506 +Rapa group was more greater than other treatment groups. Conclusions Sequential combined regimens according to the cell cycle can improve the pathological change in adriamycin-induced nephropathy rats,reduce the urine protein,increase the levels of TP and Alb,decrease the levels of TG and Chol,increase the expression of nephrin and podocin,and ameliorate kidney fibrosis.

Objective To establish the model of rat adriamycin induced nephritis (AIN)similar to the human renal glomerular disease in patho and amynology.Methods Forty Sprague Dawley rats were randomly divided into model(32) and control group (8).They were randomly divided into the first injection of adriamycin after 2 weeks,4 weeks,8 weeks and 12 weeks.Rat tail of model group vein were injected of adriamycin for two times;control group was given two injections of the same amount of normal saline through the tail veins of rats according to the method with the model group.The level of 24 hour urinary protein,serum total protein(TP),albumin(ALB),cholesterin (CH),triglyeride ( TG),serum urea nitrogen (BUN) and serum creatinine ( Cr ) were measured.The renal pathological changes were observed by light microscope and electron microscope.The expression of fibronectin(FN)and laminin (LN)was analyzed by immunohistochemistry.Matrix metalloproteinases(MMP)-2,MMP-9 and transforming grouth factor(TGF)-β1 were detected by enzyme linked immunosorbent assay.Results Compared with control group,the level of 24 hour urinary protein in AIN model at 2th,4th,8th and 12th week increased( P ＜ 0.01 ),TP and ALB were obviously decreased[ (50.7 ± 3.6),(42.2 ± 3.4),(40.4 ± 3.1 ),(41.7 ± 3.3 ) g/L vs (62.8 ±2.8)g/L;(22.2 ±1.8),(16.4 ±1.7),(14.8 ±2.1),(13.0 ±2.2)g/L vs (29.0 ± 1.3)g/L]; TG and CH in AIN model group were obviously increased [ (5.2 ± 1.4),(6.1 ± 1.5 ),(7.3 ± 1.5 ),(7.2 ± 1.2 ) mmol/L vs (0.6 ±0.3)mmol/L;(3.8 ±1.7),(5.6 ±1.9),(8.6 ±2.7),(9.6 ±1.6)mmol/L vs (1.3 ±0.1)mmol/L] ;focal segmental glomerulosclerosis( FSGS)were observed in 12th week group; The level of TGF-β1 in serum were obviously increased,the level of MMP-2 and M MP-9 reduced [ ( 151.4 ± 2.4 ),( 100.5 ± 3.1 ),(76.5 ± 3.6),( 83.7 ±3.1 ) μg/L; (73.4 ± 2.7),(58.9 ± 2.2 ),( 35.4 ± 2.0),( 33.3 ± 1.5 ) μg/L ] ; the expression and distribution of FN,LN increased significantly.Conclusion After the first large doses of adriamycin (6 mg/kg)shockb is induced,plus one week after low dose (4 mg/kg) administration in rats,the rats appear visiblely part of giomerular appearance of FSGS at the end of 12 weeks.

Objective To assess the therapeutic effects of the sequential thempy regimens according to the theory of cell cycle in adriamycin-induced nephrooathy(AIN)rats.Methods AIN model rats were randomly divided into three groups:control group(n=8),AIN model group(n=8)and treated group(n=8).The level of24hour urinary protein,serum total protein(TP),albumin(ALB),cholesterin(Chol),triglyeride(TG),serum urea nitrogen(BUN),serum creatinine(Scr)were measured.The expression of Nephrin and Podocin were analyzed by 11.12),(355.76±14.10)and(338.92±15.87)mg]were obviously higher than control group[respectively (12.18±1.38),(12.98±2.07)and(13.56±2.70)mg].The level of24 hour urinary protein in model group at 8th and 12 th week[respectively(160.64±13.72)and(126.30±14.65)mg]was obviously lower than model group(P<0.05).The levels of TP and ALB in treatment group were significantly higher in AIN model group,and westemblot indicated the expression of CTGF in treatment group was higher than that in AIN model group(P<0.05).Conclusions The sequential combined regimens can improve the pathological changes in Adriamycin-in-duced nephropathy rats,decrease the excretion of urinary protein,increase the levels of TP and ALB and decrease the levels of TG and Chol.It also can increase the expression of Nephrin and Podocin,and ameliorate kidney fibrosis.

BACKGROUND:Proteinuria varies in different glomerular diseases and even the same one. Podocin, encoded by gene NPHS2, is important in maintaining the integrity of slit diaphragm structure and avoiding proteinuria. Presently, case-control association studies were performed to investigate the genetic effect of variants in NPHS2 in a mass proteinuric glomerulopathy, minimal change disease (MCD) at first, followed by further investigation in immunoglobulin A nephropathy (IgAN). METHODS:At first, 214 northern Chinese patients with MCD and 493 geographically-matched healthy controls were enrolled. Variants of the NPHS2 were screened. SNP-2 (rs3829795:C>T, c.-670C>T) and SNP-5 (rs3738423:C>T, c.288C>T) were selected as tagging single nucleotide polymorphisms (SNP) and haplotypes were reconstructed. Association was analyzed in MCD patients. Then, the identified SNP site was analyzed in IgAN patients with mild histological changes (Haas subclass I and II). RESULTS:The C allele and CC genotype frequencies at the SNP-2 site, as well as the frequency of haplotype CC, were significantly lower in MCD patients than in healthy controls. Furthermore, they were also associated with the degree of proteinuria in MCD patients. But in IgAN patients, no such association was identified. CONCLUSION:The study suggested the polymorphism and haplotype of NPHS2 gene were associated with the genetic susceptibility and also the degree of proteinuria to MCD. Proteinuria in MCD and IgAN might occur through different mechanisms.

Objective To examine the polymorphisms of the nephrin-encoding gene,NPHS1,in patients with minimal change nephrotic syndrome(MCNS),and investigate the correlation of NPHS1 polymorphism with MCNS.Methods Seven hundred and twenty subjects,including 226 patients with histologically proven MCNS and 494 geography-matched healthy controls,were enrolled in the present study.NPHS1 gene was selected as candidate gene,and case-control correlation study was performed in a large Han Chinese population.The polymorphisms of NPHS1 G349A were determined by PCR-RFLP.The G349A alleles and genotype frequencies were compared in MCNS patients and normal controls.In addition,correlation of G349A polymorphisms with sex,age,proteinuria,blood pressure,hematuria,creatinine were analyzed in the patients with MCNS.Results ①Among 217 MCNS patients who presented with clinical and histological data,percentages of those carrying A allele(0.786 vs 0.705) and AA genotype of NPHS1 G349A(0.636 vs 0.530) were significantly higher than those of healthy controls(P<0.05).②Analysis of SNP in patients with MCNS revealed non-significant difference in urine protein of patients with different genotypes.Conclusion This study suggests that NPHS1 349G/A may be correlated with the morbidity of MCNS patients.