BACKGROUND At present, the incidence of diabetic nephropathy is increasing year by year, and there are many studies on the pathogenesis of diabetic nephropathy, but it is still not completely clear. The final pathological result of diabetic nephropathy is mainly glomerular cell fibrosis, and the roles of micro-RNA (miRNA)-29 and DNA methyl transferase (DNMTs) in cell fibrosis have been confirmed in other studies, but there is a lack of relevant research in the kidney at present. AIM To study the potential involvement of miRNA-29a-3p in fibrosis related to diabetic kidney disease (DKD). METHODS The expression of miR-29a-3p, DNMT3A/3B, fibrosis-related molecules, Wnt3a, β-catenin, Janus kinase 2, and signal transducer and activator of transcription 3 was assessed in SV40MES13 cells and diabetic mice using quantitative real-time PCR and western blotting. Furthermore, the expression changes of fibrosis-related molecules were further analyzed using immunofluorescence and immunohistochemical blotting. The renal pathological changes of DKD in each group were also studied using hematoxylin-eosin and periodate-Schiff reaction staining. RESULTS In both the in vivo and in vitro experiments, it was observed that high glucose induction significantly decreased miR-29a-3p expression. As a result of this downregulation, DKD-related fibrosis was found to be promoted, as confirmed by elevated expression levels of α-smooth muscle actin, collagen type I, and fibronectin. MiR-29a-3p targets the 3’ non-coding regions of DNMT3A and DNMT3B and inhibits their expression. Inhibition of DNMT3A and DNMT3B can reverse the effect of miR-29a-3p downregulation on DKD-related fibrosis. CONCLUSION MiR-29a-3p can regulate Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription signal pathways by regulating and inhibiting the expression of DNMT3A/3B and thus participate in the inhibition of DKD-related fibrosis.

目的 探讨lncRNA GM 10786靶向结合miR-142抑制糖尿病肾病(DN)单核巨噬细胞炎性因子分泌的作用及机制.方法 高通量转录芯片筛选DN患者与健康对照者外周血单核细胞差异表达lncRNA.实时荧光定量PCR(qRT-PCR)检测高糖刺激下THP-1细胞中GM10786的表达水平.在THP-1细胞中转染Lv-control、Lv-GM10786后,qRT-PCR测定高糖刺激下转染后细胞中pro-IL-1β和TNF-α的表达水平.采用双荧光素酶报告基因实验验证GM10786与miR-142的靶向结合及miR-142靶向调控Nrf2.THP-1细胞中转染空质粒(Control)、miR-142、以及共转染GM10786和miR-142后,qRT-PCR和Western blotting检测Nrf2和HO-1的表达水平,ELISA和Western blotting检测高糖刺激下转染细胞培养上清及细胞中IL-1β和TNF-α的表达水平.结果 与健康对照组相比,GM10786在DN患者外周血单核细胞中的表达显著下调(P＜0.05).在高糖刺激下GM10786在THP-1中的表达相较正常培养基也显著下调(P＜0.05).与HG+Lv-control组相比,HG+ Lv-GM 10786组中pro-IL-1β和TNF-α的表达水平均下调,差异有统计学意义(P＜0.001).双荧光素酶报告基因证实GM10786能够与miR-142特异性结合,Nrf2是miR-142的靶基因.与转染miR-142组相比,共转染GM10786和miR-142组的THP-1细胞中Nrf2和HO-1表达水平显著增加(P＜0.05),高糖刺激下IL-1β和TNF-α的表达水平均显著下降(P＜0.05).结论 GM10786是DN进程中重要的负调控因子,GM10786通过海绵吸附作用靶向结合miR-142和调节Nrf2表达来抑制DN中单核巨噬细胞炎性因子的分泌,该研究将有助于DN的靶向治疗.

1 病例资料 患者,女,57岁,体质量53 kg,因"多关节疼痛2年余"于2019年8月6日就诊入院.患者过去两年发生过2次膝关节疼痛,予骨化三醇、间断口服碳酸钙D3片、双磷酸盐口服治疗.用药后无全身肌肉酸痛,无发热、头痛等不良反应.2019年7月出现多关节疼痛,以右膝关节较显著,活动加重,休息可缓解.否认吸烟饮酒史、肝炎等传染病史.7月30日查骨密度示"T1-2. 7,T2-2. 9,T3-2. 4,T4-2. 8,L1-L4-2. 7,颈-4. 2,全部-4. 3".肝肾功能:总胆红素9. 2 μmol·L-1,直接胆红素1. 7 μmol·L-1;白蛋白49. 1 g· L-1 ,ALT 43 U·L-1 ,AST 41 U· L-1 ,谷氨酰基转移酶(γ-GGT)106 U·L-1,AKP 128 U·L-1,乳酸脱氢酶203 U·L-1;尿素氮9. 9 mmol· L-1,尿酸311 μmol · L-1 ,血肌酐83 μmol · L-1 ,估算肾小球滤过率67 ml·min-1.

AIMS:Our study aims to explore the role of β-catenin interaction protein-1(ICAT) in regulating peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity in mesangial cells. The abnormal ICAT expression in mesangial cells under high glucose(HG) contributes to the development of diabetes and its complications such as diabetic nephropathy (DN).METHODS:Human mesangial cells (HMCs) were cultured in either 5.5 (normal control) or 30 (high glucose) mmol/L glucose medium. Overexpression and knock-down of ICAT or β-catenin were carried out by transient transfection. PPARγ transcriptional activity was evaluated by luciferase assay. Protein-protein interactions were tested by Coimmunoprecipitation and GST-pull down assay. Cell phenotype transition of HMCs was detected by the expression level of α-SMA and fibronectin, as well as MTT assay.RESULTS:High β-catenin protein expression but low ICAT was accompanied by low PPARγ transcriptional activity in HMCs cultured in HG. By using bioinformatics prediction, protein-protein and protein-DNA interaction experimental methods, ICAT and β-catenin were confirmed to act as coactivators in regulating PPARγ transcriptional activity. Overexpression of ICAT could mitigate the decrease of PPARγ transcriptional activity and partly relieve cell phenotype transition in HMCs.CONCLUSIONS:β-catenin and ICAT interact as coactivator to modulate PPARγ transcriptional activation. In HMCs cultured in HG, the low expression of ICAT leads to low PPARγ transcriptional activation.

阿片类药物愈来愈广泛应用于治疗癌性疼痛和非癌性疼痛,其使用率的提高同时也导致其不良反应的增加,阿片类药物相关性便秘(opioid induced constipation,OIC)是最常见而持久的不良反应,OIC增加了患者的额外痛苦,明显降低患者的生活质量.现就近年来阿片类药物所致便秘的治疗药物进行综述.

目的 探讨糖尿病肾病(DN)与糖尿病视网膜病变(DR)的异质性.方法 回顾性分析2011年11月至2018年3月在陆军军医大学第二附属医院肾内科和内分泌科首次住院的429例2型糖尿病患者的临床资料,分为DN+DR组120例,DN组96例,DR组54例,DM组159例.观察各组一般资料和实验室指标,分析DN和DR的影响因素.结果 与DN组和DR组比较,DN+DR组患者收缩压(SBP)、舒张压(DBP)、尿酸(UA)、胱抑素c(Cys-c)、24 h尿蛋白、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、糖尿病周围神经病变(DPN)患病率升高,肾小球滤过率(eGFR)降低,差异有统计学意义(P＜0.05).与DR组比较,DN组患者DBP、UA、Cys-c、24 h尿蛋白、TC、LDL-C升高,eGFR降低,差异有统计学意义(P＜0.05).与DN组比较,DN+DR组患者在球性硬化比例、重度肾小管损害、重度肾间质损害、毛细血管腔K-W结节、重度间质血管病变方面更为严重(P＜0.05).DN的危险因素与性别、年龄、DR分期、eGFR、TC、三酰甘油(TG)相关(P＜0.05),DR的危险因素与病程、DN分级、DPN、DBP、eGFR相关(P＜0.05).结论 DN与DR存在发病异质性,DR并不能很好地预测DN的发生.

Previous studies reported that magnesium deficiency was associated with vascular calcifications, atherosclerosis and cardiovascular disease, which might play an independent pathogenic role in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. However, the results of these studies were somewhat underpowered and inconclusive. Literature was identified by searching PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL). We included studies that investigated the association between serum magnesium with mortality risk in CKD and ESRD patients. Unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. Twenty studies involving 200,934 participants were included, and the results showed that there was a strong association between hypomagnesemia and the risk of all-cause mortality in patients with CKD and ESRD (HR 1.32; 95% CI 1.19–1.47; p < 0.00001) (hypomagnesemia vs. normal magnesium or hypermagnesemia) after multivariable adjusted. On the contrary, hypermagnesemia was inversely associated with all-cause mortality in patients with CKD and ESRD (HR 0.86; 95% CI 0.79–0.94; p = 0.001) (per unit increase). Moreover, a significant association between hypermagnesemia and decreased risk of cardiovascular mortality was observed (HR 0.71; 95% CI 053–0.97, p = 0.03) in the adjusted model. In addition, subgroup analysis found that hypomagnesemia was strongly associated with increased all-cause mortality in hemodialysis patients (HR 1.29; 95% CI 1.12–1.50; p = 0.0005) (hypomagnesemia vs. normal magnesium or hypermagnesemia). Our results indicate that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in patients with CKD and ESRD. Further studies evaluating benefits of magnesium correction in CKD and dialysis patients with hypomagnesemia should be performed.

Diabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD). To date, mounting evidence has shown that inflammation may contribute to the pathogenesis of DN. Recent reports have shown that proteasome inhibitors display cytoprotection by reducing the phosphorylation of Akt, a serine/threonine kinase, plays a critical role in cellular survival and metabolism and can crosstalk with inflammation. Therefore, we hypothesized that MG132, specific proteasome inhibitor, could provide renoprotection by suppressing Akt-mediated inflammation in DN. In vivo , male Sprague-Dawley rats were divided into normal control group (NC), diabetic nephropathy group (DN), DN model plus MG132 treatment group (MG132), and DN model plus deguelin treatment group (Deguelin)(deguelin, a specific inhibitor of Akt). In vitro , a human glomerular mesangial cell lines (HMCs) was exposed to 5.5 mmol/L glucose (CON), 30 mmol/L glucose (HG), 30 mmol/L glucose with 0.5 umol/L MG132 (MG132) and 30 mmol/L glucose with 5 umol/L deguelin (Deguelin). Compared with NC, DN showed a significant increase in the urinary protein excretion rate and inflammatory cytokines, as well as p-Akt. Compared with CON, HMCs co-cultured with HG was notably proliferated, which is in accord with α-smooth muscle actin (α-SMA) expression. These alterations were inhibited by administration of MG132 or deguelin. In conclusion, MG132 significantly inhibits the development of DN by regulating Akt phosphorylation-mediated inflammatory activation.

Background/Aims: Geriatric nutritional risk index (GNRI) was developed as a "nutrition-related" risk index and was reported in different populations as associated with the risk of all-cause and cardiovascular morbidity and mortality. Therefore, GNRI can be used to classify patients according to a risk of complications in relation to conditions associated with protein-energy wasting (PEW). However, not all reports pointed to the prognostic ability of the GNRI. The purpose of this study was to assess the associations of GNRI with mortality in chronic hemodialysis patients. Methods: We electronically searched original articles published in peer-reviewed journals from their inception to September 2018 in The PubMed, Embase, and the Cochrane Library databases. The primary outcome was all-cause and cardiovascular mortality. We pooled unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) using Review Manager 5.3 software. Results: A total of 10,739 patients from 19 cohort studies published from 2010 to 2018 were included. A significant negative association was found between the GNRI and all-cause mortality in patients with chronic hemodialysis (OR, 0.90; 95% CI, 0.84-0.97, p = 0.004) (per unit increase) and (OR, 2.15; 95% CI, 1.88-2.46, p < 0.00001) (low vs. high GNRI). Moreover, there was also a significant negative association between the GNRI (per unit increase) and cardiovascular events (OR, 0.98; 95% CI, 0.97-1.00, p = 0.01), as well as cardiovascular mortality (OR, 0.89; 95% CI, 0.80-0.99, p = 0.03). Conclusion: Our findings supported the hypothesis that the low GNRI is associated with an increased risk of all-cause and cardiovascular mortality in chronic hemodialysis patients. Based on our literature review, GNRI has been found to be an effective tool for identifying patients with nutrition-related risk of all-cause and cardiovascular disease. (C) 2018 The Author(s) Published by S. Karger AG, Basel

目的 探讨β-连环素互作蛋白1(β-catenin-interacting protein 1,ICAT)在过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)转录活性调控中的作用及在高糖诱导系膜细胞表型转化中的意义.方法 将人肾小球系膜细胞分别用常规葡萄糖浓度(5.5 mmol/L,对照组)和高糖(30 mmol/L,高糖组)培养48 h,检测PPARγ、ICAT和β-catenin的mRNA及蛋白质表达变化.观察过表达ICAT和敲减ICAT及β-catenin对上述培养条件下系膜细胞PPARγ转录活性的影响.利用实时荧光定量PCR和蛋白质免疫印迹技术检测不同分组中细胞表型转化标志物平滑肌动蛋白d(α-smooth muscular actin,α-SMA)表达水平.利用CCK-8试剂盒检测细胞增殖水平.结果 与对照组比较,高糖培养可诱导系膜细胞表型标志蛋白α-SMA的表达上调以及系膜细胞增殖;高糖培养虽对系膜细胞PPARγ蛋白表达水平无影响(P＞0.05),但可使PPARγ转录活性明显降低(P＜0.01),同时,可抑制系膜细胞ICAT表达和促进β-catenin表达;过表达ICAT可部分升高高糖培养的系膜细胞PPARγ的转录活性(P＜0.01);在常规糖浓度条件下,敲减ICAT可降低PPARγ的转录活性(P＜0.01),敲减β-catenin表达,同样可降低PPARγ的转录活性(P＜0.01);高糖培养条件下,过表达ICAT可抑制系膜细胞α-SMA的表达与细胞增殖.结论 ICAT可能是PPARγ转录活性的重要调控分子之一,并参与介导了高糖诱导系膜细胞表型转化.

AIMS:Transforming growth factor β1 (TGFβ1) plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). However, the mechanism of its expression and activation induced by high glucose (HG) is still unclear. We mainly explored the role of ten-eleven translocation enzyme-2 (TET2) in regulating TGFβ1 expression in the process of DN.MAIN METHODS:Human mesangial cells (HMCs) and db/db mice were used to analyze the biological effects of hyperglycemia both in vivo and in vitro. Gene expression levels, cell proliferation, protein recruitment levels to TGFβ1 regulatory region, DNA methylation statues and pathological changes in kidney were tested in different groups. Short hairpin RNA(shRNA) and oral inhibitor were used to knock down or inhibit TET2 expression.KEY FINDINGS:Our study demonstrated that TET2 expression was increased in the renal cortex of db/db mice and in HMCs inducing by HG. We also found that TET2 binding was increased while DNA methylation of CpG islands was reduced in the TGFβ1 regulation region in HG, resulting in the increased expression level of TGFβ1 and cell phenotype transformation. More importantly, clinical research revealed that gradually decreased DNA methylation in the TGFβ1 regulatory region was also present in patients with diabetes and DN.SIGNIFICANCE:Our work suggests that TET2 plays an important role in the pathogenesis of DN by activating TGFβ1 expression through demethylation of CpG islands in the TGFβ1 regulatory region. This may provide a potential new therapeutic target for DN.

Objective To observe the therapeutic effect of ursodeoxycholic acid (UDCA)for patients with early diabetic nephropathy (DN). Methods From May 2016 to December 2016, a total of 40 patients with early DN (Mogensen stage Ⅲ)were diagnosed in the Nephrology Department of Xinqiao Hospital, aged30 to 59 years, with the course of disease ranging from 6 months to 30 years, were randomized equally into aprovel group (0. 15 g/d)and UDCA group (250 mg/d after meal). The levels of urinary microalbumin, urinary albumin/creatinine ratio, creatinine, and estimated glomerular filtration rate (eGFR), and the contents of inflammatory cytokines in blood and urine were measured or calculated before and in 12 months after treatment, and the results were compared between the 2 groups. Results After 12 months of treatment, the patients in the aprovel group had the urinary albumin/creatinine ratio reduced by 14. 94％ and creatinine level by 7. 73％, while eGFR increased by 8. 64％, and significant differences were noted when compared with the values before treatment (P ＜ 0. 05). Similar changes were also observed in the UDCA group (10. 39％, 6. 49％ and 7. 41％, respectively, P ＜ 0. 05). But there were no significant differences in above indicators between the 2 groups (P ＞0. 05). Aprovel treatment significantly decreased the serum levels of CRP, IL-6 and TNF-α by 13. 7％, 8. 7％ and 5. 9％, respectively, and UDCA also obviously reduced the levels by16. 2％, 14. 1％ and 16. 8％, respectively. But no significant differences were observed between the 2 groups (P ＞ 0. 05). Conclusion UDCA could decrease the urinary albumin/creatinine ratio, protect renal function and exert similar effects in the patients with stage Ⅲ.

Renal fibrosis is the most common outcome of chronic kidney disease (CKD), while the pathogenesis of renal fibrosis is not fully understood. In this study, we first showed that the progress of renal fibrosis was positively related to serum levels of indoxyl sulfate, a typical protein-bound toxin, and that there was a close correlation between serum indoxyl sulfate levels and β-catenin expression in the kidneys (r = 0.908, p < 0.001) of CKD patients. We then demonstrated that intraperitoneal injections of indoxyl sulfate (100 mg/kg/day) for 4 weeks in uninephrectomized mice explicitly induced renal fibrosis, which was accompanied by a significant activation of Wnt/β-catenin signaling. In vitro investigations in human renal tubular HK-2 cells revealed that indoxyl sulfate exhibited a potent ability to induce Wnt/β-catenin activation through the downregulation of sFRP5, a gene that codes for an extracellular antagonist of Wnt signaling, by increasing the DNA methylation level of its promoter CpG islands. The increased expression of DNA methyltransferases following the activation of ROS/ERK1/2 signaling was responsible for the DNA hypermethylation of sFRP5 induced by indoxyl sulfate. Conversely, treatment with 5-aza-2′-deoxycytidine, an inhibitor of DNA methyltransferases, significantly reduced indoxyl sulfate-induced sFRP5 downregulation and Wnt/β-catenin activation. In vivo, intraperitoneal injections of recombinant sFRP5 protein or 5-aza-2′-deoxycytidine substantially alleviated renal fibrosis in indoxyl sulfate-treated uninephrectomized mice. Our results suggest that indoxyl sulfate promotes renal fibrosis through the induction of DNA hypermethylation of sFRP5, and thereafter the activation of Wnt/β-catenin signaling. These findings provide new insights into the pathogenesis of renal fibrosis in CKD patients.

Objective To investigate the role of tet methylcytosine dioxygenase 2 (TET2) in the regulation of transforming growth factor-β1 (TGF-β1) expression in human glomerular mesangial cells induced by high glucose.Methods Cultured human glomerular mesangial cells were divided into normal control group (5.5 mmol/L glucose) and high glucose group (30.0 mmol/L glucose) which was cultured for 12 h to 72 h.The gene expression of TET2 in mesangial cells were inhibited by small molecule chemical called SC1,and which were divided into high glucose group (30.0 mmol/L glucose+ DMEM),DMSO group (30.0 mmol/L glucose+0.1％DMSO) and SC1 group (30.0 mmol/L glucose+3 μmol/L SC1).The mRNA and protein expression of TGF-β1,TET1 to 3 and α-smooth muscle actin (α-SMA) was detected by quantitative real-time PCR and Western blotting.Methylation of CpG islands in the regulation region of TGF-β1 was detected by bisulfite sequencing PCR (BSP).The activity of mesangial cell proliferation was assessed by colorimetry of thiazolyl blue (MTT).Results Compared with normal control group,the mRNA and protein expression of TET2 in mesangial cells induced by high glucose was increased significantly in a time-dependent manner (all P ＜ 0.05),but the expression of TET1 and TET3 was not affected.Meanwhile methylation rate of 4 CG sites from 24 h to 72 h were decreased in the first exon of TGF-β1 (P ＜ 0.01),but not in the promoter.Compared with high glucose group,when the expression of TET2 was inhibited by SC1,the methylation rate of TGF-β1 was recovered evidently (P ＜ 0.05),the mRNA and protein expression of TGF-β1 and α-SMA was suppressed,and the proliferation of mesangial cells was decreased (all P ＜ 0.05).Conclusions Demethylation of the CpG island mediated by TET2 may play an important role in the expression of TGF-β1 and mesangial cell phenotype transformation induced by high glucose.

目的 探讨伴与不伴水肿的糖尿病肾病(diabetic nephropathy,DN)患者的临床与病理特征.方法 将病理诊断明确的170例DN患者分成水肿型DN组(edema DN,E-DN)和非水肿型DN组(nonedema DN,NE-DN),比较两组患者的临床和病理特征及预后间的差异.结果 与基线值比较,E-DN组肾脏病理改变重,糖化血红蛋白(HbA1c)、血压(BP)、总胆固醇(TC)、24 h尿蛋白定量＞3.5g的百分比等均显著高于NE-DN组(P ＜0.05,P＜0.01),而eGFR和血浆白蛋白(ALB)、尿比重、尿渗透压等均显著低于NE-DN组(P ＜0.05,P＜0.01).随访2年,E-DN组eGFR下降速率均显著大于NE-DN组(P＜0.05),肾脏终点事件发生率、肾外并发症发病率也显著高于NE-DN组(P＜0.05).生存分析显示E-DN组预后差(X2=17.460,P＜0.01).危险因素分析发现肾活检时ALB(RR=0.938,P=0.004)、eGFR(RR=0.985,P＜0.01)、肾脏间质病变(RR=1.236,P=0.012)、TC(RR=1.192,P=0.015)、水肿(RR =6.412,P＜0.01)是DN肾脏死亡的独立危险因素.结论 伴有水肿的DN患者较不伴有水肿的DN患者血糖控制较差、ALB低、脂质代谢紊乱、肾脏间质病变重、肾脏中位生存时间短,水肿为影响肾脏死亡的独立危险因素.

目的 建立延肾胶囊中川芎嗪的含量HPLC测定方法.方法 检测院内制剂延肾胶囊中川芎嗪的含量.采用Symmetry C-18(150 mm×4.6 mm,5μm)色谱柱,流动相为甲醇-醋酸铵(pH=8.6)-四氢呋喃缓冲液(20:75:5),检测波长为285 nm,流速1.0 ml/min.结果 川芎嗪在2.0～40.0 μg/ml范围内呈良好线性关系,r=0.9996 (n=6),平均回收率为100.70％,RSD=1.62％.结论 高效液相色谱法能够准确测定延肾胶囊中川芎嗪的含量,该法操作简单,重现性好,可用于该制剂的含量测定和质量控制.

Objective To investigate the role of DNA methylation changes in the regulatory region of TGFB1 gene in patients with diabetic nephropathy（DN）.Methods According to the WHO 1999 guideline for diabetes mellitus diagnosis and classification standard,91 patients who were hospitalized in June 2013 to May 2015 and diag-

Objective To investigate the impact of chronic kidney disease (CKD) on patients' cognitive function and its related factors.Methods A total of 266 patients diagnosed with 3-5 stage CKD,age ＞ 18 years,enrolled as outpatients or inpatients in our nephrology department from June 2014 to June 2015,were subjected this study.According to the value of estimated glomerular filtration rate (eGFR),the patients were divided into stage 3 CKD group (CKD3) (60 mL/min ＞ eGFR≥ 30 mL/min,n =92),stage 4 CKD group (CKD4) (30 mL/min ＞eGFR≥ 15 mL/min,n=96) and stage 5 CKD group (CKD5) (eGFR ＜ 15 mL/min,n =78).Eighty cases of control were recruited from hospital staffs following the criteria:normal appearance,eGFR ＞ 90 mL/min and matched age,sex,and education level with the patients.Minimental state examination (MMSE) was performed to evaluate the subjects' cognitive function.The levels of serum creatinine (Cr),urea nitrogen (UN),uric acid (UA),cholesterol (CHE),high density lipoprotein cholesterol (HDL-C),and low density lipoprotein cholesterol (LDL-C) were determined by OLYMPUS AU2700 automatic biochemical analyzer.Hemoglobin (Hb) level was examined by XFA9500 automatic blood cell analyzer.All data were analyzed using statistical software SSPS 13.0.Results The overall incidence of cognitive impairment in stage 3-5 CKD groups was remarkably higher (33.1％) than that of the control (7.5％).Moreover,the incidence of cognitive impairment was increased along the CKD stage from 3 to 5.In the CKD-4 and-5 groups the increased incidence was statistically significant (P ＜ 0.01).In addition,the MMSE score was significantly decreased from stage 3 to 5 compared to the control (CKD 3 group,P ＜ 0.05;CKD-4 and-5 groups,P ＜ 0.01).The MMSE score was negatively correlated with the factors of age,UN,Cr and UA (P ＜ 0.01),but positively correlated with Hb (P ＜ 0.05) and eGFR (P ＜ 0.01).Conclusion CKD affects the patients' cognitive function significantly.The incidence and severity of cognitive impairment are related closely with the levels of blood UN,Cr,UA,patients' age,Hb concentration and eGFR.

Visfatin, a recently discovered adipocytokine, has been shown to have an important role in the pathogenesis of diabetic nephropathy (DN). The farnesoid X receptor (FXR), a ligand-activated nuclear receptor, plays a protective role in DN. The regulation between FXR and visfatin and their interaction in DN has not been well established. In this study, we reported that FXR agonist GW4064 reduced high glucose induced human mesangial cells (HMCs) inflammation, fibrosis and proliferation by downregulating visfatin expression, which can be blunted by exogenous visfatin treatment. Moreover, luciferase reporter assay showed FXR regulated visfatin transcription activity probably by binding to the -1607 bp and -1192 bp region of the visfatin promoter. In vivo study also showed that GW4064 ameliorated the progression of DN in db/db mice with a decreased visfatin expression. These findings suggest that FXR activation delayed the progression of diabetic nephropathy and this effect is through downregulating visfatin.

BACKGROUND:Interleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations.METHODS:The PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity.RESULTS:A total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85-1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79-1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85-1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79-1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients.CONCLUSION:This meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed to confirm our results.