Vitamin D-vitamin D receptor alleviates oxidative stress in ischemic acute kidney injury via upregulating glutathione peroxidase 3.

Vitamin D receptor was previously reported to be protective in acute kidney injury (AKI) with the mechanism unclear, while the role of renal localized glutathione peroxidase 3 (GPX3) was not illustrated. The present study aims to investigate the role of GPX3 as well as its correlation with vitamin D-vitamin D receptor (VD-VDR) in ischemia-reperfusion (I/R)-induced renal oxidative stress injury. We showed that the expression of GPX3 and VDR were consistently decreased in renal tissues of I/R-related AKI patients and mice models. VDR agonist paricalcitol could reverse GPX3 expression and inhibit oxidative stress in I/R mice or hypoxia-reoxygenation (H/R) insulted HK-2 cells. VDR deficiency resulted in aggregated oxidative stress and severer renal injury accompanied by further decreased renal GPX3, while tubular-specific VDR overexpression remarkably reduced I/R-induced renal injury with recovered GPX3 in mice. Neither serum selenium nor selenoprotein P was affected by paricalcitol administration nor Vdr modification in vivo. In addition, inhibiting GPX3 abrogated the protective effects of VD-VDR in HK-2 cells, while GPX3 overexpression remarkably attenuated H/R-induced oxidative stress and apoptosis. Mechanistic probing revealed the GPX3 as a VDR transcriptional target. Our present work revealed that loss of renal GPX3 may be a hallmark that promotes renal oxidative stress injury and VD-VDR could protect against I/R-induced renal injury via inhibition of oxidative stress partly by trans-regulating GPX3. In addition, maintenance of renal GPX3 could be a therapeutic strategy for ischemic AKI.

Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients.

BACKGROUND: The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. METHODS: Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. RESULTS: Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1ß, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764-0.924). CONCLUSION: Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes.

Lipid microsphere-coated PGE1 improves peritoneal transport and reduces inflammation in peritoneal dialysis: A randomized clinical pilot trial.

OBJECTIVE: To evaluate the effects of lipid microspheres coated with prostaglandin E1 (lipo-PGE1) on peritoneal transport function and inflammation in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: In total, 89 patients were randomly allocated to the lipo-PGE1 and control groups. All the patients received conventional treatment, and those in the lipo-PGE1 group received lipo-PGE1 intravenously for 2 weeks. The levels of ß2-microglobulin (ß2-MG), cystatin C, albumin, urea, creatinine, interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured before and at 1 and 2 weeks after treatment. RESULTS: In the lipo-PGE1 group, the peritoneal clearance rates of ß2-MG, cystatin C, and albumin were significantly increased comparing with pre-treatment values, and the IL-6 appearance rate (AR) in the peritoneal dialysate and the serum levels of IL-6 and hs-CRP were markedly decreased (p < 0.05). The lipo-PGE1 group had significantly higher peritoneal clearance rates of ß2-MG and cystatin C and lower IL-6 AR in the peritoneal dialysate than the control group (p < 0.05). CONCLUSIONS: Lipid microspheres coated with prostaglandin E1 may increase the peritoneal clearance of moderately sized molecules and macromolecules with insignificant effect on the clearance of small molecules. The reduction in IL-6 level following treatment with lipo-PGE1 may alleviate inflammation.

Whole exome sequencing identified a novel mutation (p.Ala1884Pro) of ß-spectrin in a Chinese family with hereditary spherocytosis.

BACKGROUND: Hereditary spherocytosis (HS) is an inherited disorder of erythrocyte. The typical feature of HS is the presence of spherical-shaped erythrocytes on the peripheral blood smear. According to previous studies, more than five candidate genes, such as ANK1, SPTB, SPTA1, SLC4A1 and EPB42 have been identified in HS patients. METHODS: In the present study, a Chinese HS family was investigated. The proband suffered from pathologic jaundice and splenomegaly. A blood test and peripheral blood smear experiment further confirmed the diagnosis of HS. We selected the proband to perform the whole exome sequencing. RESULTS: After data filtering and co-segregation analysis, we identified 12 mutations in affected members that were absent in healthy members. In consideration of the inheritance pattern, Online Mendelian Inheritance in Man clinical phenotypes, Toppgene function and American College of Medical Genetics classification, we considered the novel mutation (c.5650G > C/p.Ala1884Pro) of ß-spectrin (SPTB) to be the genetic lesion in this family. The novel mutation, resulting in a substitution of alanine by proline, may lead to transformation of the SPTB protein structure, which affects the binding between SPTB and ankyrin. CONCLUSIONS: The present study confirmed the hereditary red blood cell membrane disorders at a molecular level and expanded the spectrum of SPTB mutations. This may contribute to the clinical management and genetic counseling with respect to HS.

Polyethylene glycol loxenatide (PEX168) in subjects with renal impairment: A pharmacokinetic study.

AIMS: Type 2 diabetes mellitus (T2DM) is commonly complicated by renal impairment. Polyethylene glycol loxenatide (PEX168) is a novel long-acting glucagon-like peptide-1 receptor agonist for T2DM. PEX168 pharmacokinetics was studied to identify requirements for dose-modification in T2DM complicated by renal impairment. METHODS: This was a single-centre, open-labelled, parallel-group, single-dose, phase I clinical trial of patients with mild and moderate renal impairment, and with or without T2DM. Age-, sex- and body mass index-matched subjects with normal renal function, and with or without T2DM were recruited as controls. Subjects received a single abdominal subcutaneous injection of PEX168 200 µg. Pharmacokinetic samples were taken at 0, 24, 48, 72, 96, 120, 144, 216, 312, 480, 648 and 720 hours. RESULTS: Twenty-three patients were included in the pharmacokinetics analysis. Vz/F and CL/F were lower in the moderate impairment group than in the other groups. The mean t1/2 (163 hours) in the moderate impairment group was prolonged compared to the mild impairment (117 hours) and normal (121 hours) groups. AUC0-inf increased by 13 and 100.7% in patients with mild and moderate renal impairment, respectively. Most adverse events were mild gastrointestinal disorders, with only 1 serious adverse event observed. CONCLUSION: A single dose of 200 µg of PEX168 was in general well tolerated in patients with renal impairment. The in vivo clearance rate of PEX168 in patients with moderate renal impairment is slower than in patients with mild renal impairment and normal renal function and dose adjustment might be required (ClinicalTrials.org #NCT02467790).

Niban protein regulates apoptosis in HK-2 cells via caspase-dependent pathway.

Purpose: To investigate whether Niban protein plays a role in renal interstitial fibrosis by regulating renal tubular epithelial cell apoptosis and explore the underlying mechanism. Methods: Unilateral ureteral obstruction (UUO) model was performed in C57B/6J mice, and divided into sham operation group and groups of days 3, days 7, and days 14. Niban expression was detected by immunohistochemistry and Western blot. TUNEL assays were used to detected apoptosis. Niban siRNA and overexpression Niban plasmid were transfected in HK-2 cells respectively to explore apoptosis related mechanisms of Niban during angiotensin II (AngII) - and endoplasmic reticulum (ER) stress-induced injury. Results: With the development of obstruction, Niban's expression decreased gradually while apoptosis increased. Silencing of Niban not only increased the AngII- and ER stress-induced apoptosis, but also promoted the expression of caspase 8, caspase 9, Bip, and Chop. Overexpression of Niban reduced AngII-induced apoptosis and the expression of caspase 8 and caspase 9. Conclusions: Niban protein is involved in apoptosis regulation in HK-2 cells, and most likely via caspase-dependent pathway.

[Early diagnosis, prevention and treatment for calcific uremic arteriolopathy].

Calcific uremic arteriopathy (CUA), termed calciphylaxis, is a rare but highly fatal clinical syndrome. There is no clearly laboratory diagnostic criteria for CUA. The medium and small arterial calcification and microthrombosis discovered by skin biopsy, radiologic imaging，bone scan and the evidence of activation of the bone morphogenetic protein signal (BMPs) transduction pathway are useful for early diagnosis of this disease. The common therapies (including intravenous sodium thiosulfate (STS) and bisphosphonates, hyperbaric oxygen therapy and other symptomatic supports) are used for the management of wounds, pain, nutrition, dialysis and so on. Controlling the chronic kidney disease-mineral and bone disorder (CKD-MBD) and some complications of dialysis and drugs (such as warfarin, active vitamin D) can prevent CUA. However, CUA patients still have poor prognosis and high mortality. Since some patients progress rapidly, it is of great importance to make early diagnosis and provide effective treatments with multidisciplinary management.

Whole-Exome Sequencing Identifies Two Novel TTN Mutations in Chinese Families with Dilated Cardiomyopathy.

OBJECTIVES: Dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death. So far, only 127 mutations of Titin(TTN) have been reported in patients with different phenotypes such as isolated cardiomyopathies, purely skeletal muscle phenotypes or complex overlapping disorders of muscles. METHODS: We applied whole-exome sequencing (WES) to investigate cardiomyopathy patients and a cardiomyopathy-related gene-filtering strategy was used to analyze the disease-causing mutations. Sanger sequencing was applied to confirm the mutation cosegregation in the affected families. RESULTS: A nonsense mutation (c.12325C>T/p.R4109X) and a missense mutation (c.17755G>C/p.G5919R) of TTN were identified in 2 Chinese DCM families, respectively. Both mutations were cosegregated in all affected members of both families. The nonsense mutation is predicted to result in a truncated TTN protein and the missense mutation leads to a substitution of glycine by arginine. Both variants may cause the structure changes of titin protein. CONCLUSIONS: We employed WES to detect the mutations of DCM patients and identified 2 novel mutations. Our study expands the spectrum of TTN mutations and offers accurate genetic testing information for DCM patients who are still clinically negative.

[Clinical characteristics and the factors relevant to peritoneal transport function in patients with continuous ambulatory peritoneal dialysis].

OBJECTIVE: To observe the clinical characteristics with different peritoneal transport type in patients with continuous ambulatory peritoneal dialysis (CAPD), and to investigate the factors associated with peritoneal transport function.
 Methods: The clinical data of 158 CAPD patients were analyzed retrospectively. According to peritoneal equilibration test, a method for evaluation of the peritoneal transport function, the patients were divided into 2 groups: a high average and high peritoneal transport group (Group A, n=84) and a low average and low peritoneal transport group (Group B, n=74). The demographics, clinical biochemical indexes and the incidence of cardiovascular complications were compared between the 2 groups. Logistic regression analysis was used to find the factors relevant to peritoneal transport function.
 Results: The level of serum albumin (ALB) in the Group B was significantly higher than that in the Group A (P<0.05). The 4 h dialysate/plasma creatinine (D/Pcr), high-sensitivity C-reactive protein (hs-CRP), body mass index (BMI), and the rates of cardiovascular complications in the Group A were significantly higher than those in the Group B (P<0.05). Correlation analysis showed that the D/Pcr was positively correlated with the BMI, serum hs-CRP and cardiovascular complications (r=0.179, 0.373 and 0.426, respectively, P<0.05), while it was negatively correlated with ALB (r=-0.393, P<0.01). Logistic regression analysis showed that the high BMI (OR=1.178, P<0.05), cardiovascular complications (OR=5.035, P<0.01), and the low serum ALB (OR=0.852, P<0.01) were the risk factors for high peritoneal transport.
 Conclusion: The serum ALB level, BMI and the cardiovascular complications are associated with high peritoneal transport, which are useful markers for predicting the peritoneal transport function before peritoneal dialysis.

Safety and efficacy of mizoribine treatment in nephrotic syndrome complicated with hepatitis B virus infection: a clinical study.

Objective The objective of this study is to explore the efficacy and safety of mizoribine (MZR) in treating nephrotic syndrome patients afflicted with hepatitis B virus (HBV). Methods The present study included 36 nephrotic syndrome patients accompanied with HBV infection. A draft of MZR (150-200 mg/d), methylprednisolone (0.6-0.8 mg/kg·d), and entecavir (0.5 mg/d) was administered to study patients over 24 weeks. The serum albumin (AlB), 24-h urine protein (24-U-TP), liver and renal functions, and HBV-DNA were quantified before and at 2, 4, 8, 12, 16, 20, and 24 weeks after the treatment. The adverse responses were recorded. Results The AlB levels of patients increased gradually after comprehensive treatment, while the 24-U-TP, serum cholesterol, and triglyceride (TG) levels declined gradually. The changes at 24 weeks post-treatment were statistically significant. Compared with the levels before treatment, the HBV-DNA, transaminase, and renal functions of the patients were not significantly altered after the treatment. No evident adverse response was found. Conclusion Treatment using MZR in combination with methylprednisolone and entecavir in HBV-positive nephrotic syndrome patients displays significant efficacy with a low incidence of adverse reactions.

Obesity indices for prediction of chronic kidney disease: a cross-sectional study in 26 655 Chinese adults.

OBJECTIVE: To investigate the associations between chronic kidney disease (CKD) and body mass index (BMI), waist circumference(WC), waist-to-height ratio (WheiR) in Chinese adults.
 METHODS: A total of 26 655 participants, who voluntarily attended annual health examination at the Health Management Center in the Third Xiangya Hospital of Central South University from June 2013 to February 2014, were enrolled for this study. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed.
 RESULTS: The prevalence rate of CKD was 9.6% and 3.1% in male and female subjects, respectively. Multivariate logistic regression analysis showed that BMI, WC and WheiR were independent risk factors for CKD in diabetic male and hypertensive male subjects (P<0.01). However, no association between these obesity indices and CKD was found in women after multivariate adjustment. In diabetic male subjects, when BMI≥28.7 kg/m(2), WC=90.7 cm and WheiR=0.56, the sensitivity and specificity prediction for CKD was 24.8%, 58.5%, 45.5% and 83.3%, 54.4%, 69.6%, respectively. In hypertensive male subjects, when the optimum cut-off points for BMI, WC and WheiR were ≥27.0 kg/m(2), 91.2 cm and 0.54, the sensibility prediction for CKD were 41.0%, 47.0% and 50.1%, respectively, while the specificity prediction were 68.0%, 63.0% and 61.4%, respectively. The area under the ROC curve of BMI, WC, WheiR for CKD prediction were 0.56, 0.57, 0.59 in diabetic male subjects and 0.54, 0.56, 0.57 in hypertensive male subjects, respectively.
 CONCLUSION: BMI, WC and WheiR are associated with the increased risk for CKD in diabetic or hypertensive male subjects. However, the value for these obesity indices is limited in screening CKD.

Application of GC-MS coupled with chemometrics for scanning serum metabolic biomarkers from renal fibrosis rat.

Renal interstitial fibrosis closely relates to chronic kidney disease and is regarded as the final common pathway in most cases of end-stage renal disease. Metabolomic biomarkers can facilitate early diagnosis and allow better understanding of the pathogenesis underlying renal fibrosis. Gas chromatography-mass spectrometry (GC/MS) is one of the most promising techniques for identification of metabolites. However, the existence of the background, baseline offset, and overlapping peaks makes accurate identification of the metabolites unachievable. In this study, GC/MS coupled with chemometric methods was successfully developed to accurately identify and seek metabolic biomarkers for rats with renal fibrosis. By using these methods, seventy-six metabolites from rat serum were accurately identified and five metabolites (i.e., urea, ornithine, citric acid, galactose, and cholesterol) may be useful as potential biomarkers for renal fibrosis.

Fluorofenidone protects against renal fibrosis by inhibiting STAT3 tyrosine phosphorylation.

Signaling through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, especially JAK2/STAT3, is involved in renal fibrosis. Fluorofenidone (FD), a novel pyridone agent, exerts anti-fibrotic effects in vitro and in vivo. Herein, we sought to investigate whether FD demonstrates its inhibitory function through preventing JAK2/STAT3 pathway. In this study, we examined the effect of FD on activation of rat renal interstitial fibroblasts, glomerular mesangial cells (GMC), and expression of JAK2/STAT3. Moreover, we explored the histological protection effects of FD in UUO rats, db/db mice, and phosphorylation of JAK2/STAT3 cascade. Our studies found that pretreatment with FD resulted in blockade of activation of fibroblast and GMC manifested by fibronectin (FN) and α-smooth muscle actin (α-SMA) protein expression and decline of STAT3 tyrosine phosphorylation induced by IL-6 or high glucose. In unilateral ureteral obstruction rats and a murine model of spontaneous type 2 diabetes (db/db mice), treatment with FD blocked the expression of FN and α-SMA, prevented renal fibrosis progression, and attenuated STAT3 activation. However, FD administration did not interfere with JAK2 activation both in vivo and in vitro. In summary, the molecular mechanism by which FD exhibits renoprotective effects appears to involve the inhibition of STAT3 phosphorylation.

Peroxiredoxin 1 inhibits the oxidative stress induced apoptosis in renal tubulointerstitial fibrosis.

AIM: Apoptosis is one of the most important mechanisms underlying renal tubulointerstitial fibrosis. We identified a role of protein Peroxiredoxin 1 (Prx1) in protecting apoptosis occurred in tubular epithelial cells of the rat and human kidney. METHODS: Immunohistochemistry (IHC) staining was used to detect Prx1 expression in kidney derived from unilateral-ureteral obstruction (UUO) rats or patients with obstructive nephropathy. Modulation of Prx1 expression by transfecting siRNA and overexpression plasmid approach were carried out in NRK-52E (rat kidney tubular epithelial cell line) cells. UUO-induced apoptosis was determined using TUNEL assay. RESULTS: Immunohistochemistry staining showed that Prx1 expressed in the cytoplasm of renal tubular epithelial cells, in the kidneys of UUO rats. The reduction was confirmed by both IHC and real-time polymerase chain reaction following a course of renal tubulointerstitial fibrosis in UUO rats and a decrease of Prx1 occurred concomitantly with an elevation of TUNEL-positive cells. Fluorofenidone (AKF-PD), a new anti-tubulointerstitial fibrotic agent, attenuated Prx1 reduction in UUO rats. Furthermore, hydrogen peroxide (H2 O2 )-derived oxidative stress activated p38 MAPK, and induced apoptosis in NRK-52E cells; knockdown of Prx1 sensitized both events in NRK-52E cells, and overexpression of Prx1 diminished the apoptosis and the phosphorylation of p38 CONCLUSION: Downregulation of Prx1 occurred in renal tubular epithelial cells of UUO rats and patients with obstructive nephropathy. Prx1 may alleviate the pathogenesis by inhibiting H2 O2 -induced apoptosis via inhibiting the p38 MAPK pathway. Prx1 may represent a useful target for a protective therapy towards renal tubulointerstitial fibrosis.

[Effect of alprostadil on serum level of miRNA-155 in uremic patients].

OBJECTIVE: To investigate the serum levels of microRNA-155 (miR-155) and interleukin-6 (IL-6) in uremic dialysis patients and to evaluate the effect of alprostadil (A) on them.
 METHODS: A total of 81 chronic kidney disease (CKD) uremic patients were divided into 4 groups: the peritoneal dialysis group (PD group, n=20), the peritoneal dialysis plus alprostadil group (PD+A group, n=20), the hemodialysis group (HD group, n=21), the hemodialysis plus alprostadil group (HD+A group, n=20). Sixteen healthy people were taken as the normal control (NC) group. The peripheral blood of all objects were collected for serum preparation. The expression of miRNA-155 was determined by real-time qPCR and the serum level of IL-6 was measured by ELISA. Experimental and clinical data of all the objects were collected.
 RESULTS: Serum levels of miRNA-155 and IL-6 were increased in all dialysis patients groups compared with NC group (P<0.05); miRNA-155 expression in PD+A group was down-regulated compared with PD group or HD group (P<0.05); the levels of IL-6 in PD+A and HD+A group were significantly decreased compared with PD group or HD group (P<0.05). Correlation analysis showed that serum level of miR-155 was positively correlated with the level of IL-6 as well as high-sensitivity C-reactive protein (hs-CRP), while miR-155 was negatively correlated with HDL and albumin (P<0.01). Linear stepwise regression analysis indicated that serum miR-155 was independently associated with albumin and hs-CRP.
 CONCLUSION: Serum miRNA-155 and IL-6 in uremic dialysis patients were remarkably increased compared to healthy objects. Serum miRNA-155 was positively correlated with the level of IL-6 as well as hs-CRP, while miR-155 was negatively correlated with HDL and albumin. Alprostadil could ameliorate the inflammatory conditions of uremic dialysis patients by inhibition of the IL-6 expression. Serum miRNA-155 may be a novel target for the treatment of uremic dialysis patients.

Pharmacokinetics of single-dose morinidazole in patients with severe renal impairment.

OBJECTIVE: To evaluate the pharmacokinetics of morinidazole in individuals with severe renal impairment (RI). METHODS: This open-label Phase I study enrolled healthy volunteers and patients with severe RI aged 18 - 65 years. All subjects received a single infusion of sodium chloride injection with 500 mg morinidazole. Plasma and urine concentration of morinidazole and one of its metabolites (M4-1) were evaluated by using HPLC-UV and HPLC-MS/MS respectively. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.0 software. RESULTS: 22 individuals (healthy: n = 11, severe RI: n = 11) received morinidazole. In both groups, maximum plasma concentration of morinidazole was reached within 1 hour, while the tmax of M4-1 differed greatly. Both AUC0-t and AUC0-∞ of morinidazole were 1.4 times higher in patients with severe RI, while M4-1 were over 7 times higher than healthy groups. Renal excretion of unchanged morinidazole was decreased by 65% in patients with RI, and M4-1 was decreased by 72%. Apparent correlation between CLcr and CL, AUC, t1/2 and CLr were seen in two groups. CONCLUSIONS: A single dose of 500 mg morinidazole is well tolerated. Changes in pharmacokinetic parameters of morinidazole and M4-1 are seen in patients with RI and may be clinically important.

Expression of Niban in renal interstitial fibrosis.

AIM: Apoptosis is one of the most important mechanisms underlying renal interstitial fibrosis. We identified the role of protein Niban in apoptosis of tumour cells. The purpose of this study was to assess the expression of Niban in renal interstitial fibrosis of humans and rats. METHODS: Immunohistochemistry was used to detect Niban in patients with obstructive nephropathy. Proteomics and gene array analysis were performed to screen different molecules involved in the pathophysiology of unilateral-ureteral obstruction rats. We confirmed Niban using immunohistochemistry and Western blot in renal cortex of UUO rats and HK-2 cells. TUNEL assay and flow cytometry revealed apoptosis of renal tubular cells. siRNA and overexpression plasmid were transfected specifically to study the possible function of Niban. RESULTS: Niban was decreased apparently in renal tubular cells of patients with obstructive nephropathy, compared with controls. Niban decreased in renal cortex of UUO rats and transforming growth factor-ß1 (TGF-ß1)-stimulated HK-2 cells. siRNA of Niban increased apoptosis of HK-2 cells. TGF-ß1 also increased apoptosis of HK-2 cells. Overexpression of Niban failed to diminish apoptosis of HK-2 cells induced by TGF-ß1. CONCLUSIONS: Niban decreased in renal tubular cells of patients of obstructive nephropathy, UUO rats and TGF-ß1 stimulated HK-2 cells. Suppressing Niban increases apoptosis in HK-2 cells. Niban may be associated with apoptosis of HK-2 cells.

Implementation of a continuous quality improvement program reduces the occurrence of peritonitis in PD.

OBJECTIVE: To investigate the causes of peritonitis in patients with peritoneal dialysis (PD) using continuous quality improvement (CQI) to develop effective interventions and reduce the occurrence of peritonitis. METHODS: A quality control team consisting of 10 members, including the department head, four nephrologists and four nurses, all specialized in PD care, and the head nurse, was established at the Peritoneal Dialysis Center of the Third Xiangya Hospital of Central South University. All patients with peritonitis occurring between 1 July 2010 and 31 December 2011 (pre-CQI period) were analyzed and compared with data obtained between January 2012 (implementation of CQI) and March 2013 to investigate possible causes of peritonitis and to develop corresponding interventions. Fishbone analysis, including laboratory parameters, was carried out monthly. RESULTS: Gastrointestinal tract dysfunction, nonstandard procedures and malnutrition were found to be the top three risk factors for peritonitis. Gastrointestinal tract dysfunction was the likely cause of peritonitis in 42.8% of the subjects before CQI and 36.0% after CQI (p<0.05). Nonstandard procedures were the cause of peritonitis in 33.3% of the subjects before CQI and 24.0% after CQI (p<0.05). The overall incidence of peritonitis reduced from once every 40.1 patient months before the CQI to once every 70.8 patient months after CQI (p<0.05). The incidence of Gram-positive bacteria peritonitis reduced from once every 96.9 patients per month before CQI to once every 209.1 patient months after CQI (p<0.05), whereas the incidence of Gram-negative bacteria peritonitis reduced from once every 234.2 patient months before CQI to once every 292.8 patient months after CQI. CONCLUSION: CQI can effectively reduce the occurrence of PD-related peritonitis.

[Changes of plasminogen activator inhibitor-1 and D-dimer during continuous blood purification and related factors].

OBJECTIVE: To observe the changes of plasminogen activator inhibitor-1 and D-dimer during continuous blood purification (CBP) and related factors. METHODS: Sixteen patients who were diagnosed with multiple organ dysfunction syndrome (MODS) were randomly divided into 2 groups: 8 patients received standard continuous blood purification with heparin anticoagulation, and the other 8 received CBP without anticoagulation. Ten normal blood samples were collected from healthy volunteers as controls. All patients underwent CBP for 8 h. Blood was taken from those patients at 0, 15, 60, 120 and 480 min during the CBP. Plasma plasminogen activator inhibitor-1, D-dimer and serum TNF-α and IL-1ß were measured by ELISA. RESULTS: Plasma levels of PAI-1 and D-dimer were increased significantly compared with those in the control group (P<0.05). Plasma level of PAI-1 was reduced (P<0.05) and D-dimer was increased (P<0.05) after the CBP. The level of plasma PAI-1 in the heparin group was significant reduced compared with the group of CBP without anticoagulation (P<0.05). There was negative correlation between the level of PAI-1 and the dosage of heparin used during a CBP session in the heparin group (r=-0.746, P<0.001). CONCLUSION: The level of PAI-1 and D-dimer is higher in patients with MODS than that in the normal controls. After the CBP treatment, there is significant decrease in PAI-1 and increase in D-dimer in both groups. Heparin used during CBP can reduce PAI-1 which intensifies its function of anticoagulation.

[Advances in post-translational modifications of cGAS in innate immunity].

As a member of the nucleotidyltransferase family, cyclic guanosine monophosphate-adenosine monophosphate synthase (cyclic GMP-AMP synthase, or cGAS) is primarily involved in innate immunity as a nucleic acids sensor that activates its downstream pathway and regulates type I interferon synthesis. The regulation of cGAS function is correlated with the bacterial and viral infections, autoimmune diseases, tumors, and other diseases. Besides, post-translational modification is one of the most in-depth and extensive ways of cGAS function adjustment. There are mainly six types of post-translational modifications (PTMs) of cGAS, including phosphorylation, acetylation, ubiquitination, sumoylation, peptide chain cleavage, and glutamylation. This article not only systematically summarizes how PTMs of cGAS regulate the functions of cGAS under different physiological and pathological conditions, but also probes deep into the potential of PTMs as therapeutic targets.