507例2型糖尿病合并慢性肾脏病患者肾活检的临床病理特点

目的 总结和分析糖尿病肾病(diabetic kidney disease,DKD)与非糖尿病肾病(non-diabetic kidney disease,NDKD)患者临床病理特点,为临床2型糖尿病合并慢性肾脏病患者肾活检指征提供循证医学证据.方法 通过南方医科大学南方医院大数据库收集2002年2月至2018年6月在该院接受肾活检的2型糖尿病合并慢性肾脏病患者,并根据肾活检结果将其分为DKD组和NDKD组(包括DKD合并NDKD),比较两组间临床表现及病理类型特点,并采用Logistic回归模型分析DKD和NDKD患者的相关因素.结果 共纳入507例患者,DKD患者114例(22.5%),NDKD患者393例(77.5%).病理表现:NDKD的最常见病理类型为膜性肾病(30.0%)和IgA肾病(19.1%),其中有5.6%患者为DKD合并NDKD.临床表现:与NDKD组患者相比,DKD组患者有更长的糖尿病史(>1年,76.3%比36.1%,P<0.001),更易发生糖尿病视网膜病变(42.1%比4.8%,P< 0.001),24h尿蛋白量更高[3.69(1.70,6.74)g比2.21 (0.91,4.97)g,P<0.001],血肌酐更高[117.5 (85.8,194.5) μmol/L比89.0 (68.0,143.8) μmol/L,P<0.001],血红蛋白更低[(105.07±20.85) g/L比(124.41±25.02) g/L,P=0.002],胆固醇更低[(5.69±1.87) mmol/L比(6.43±2.75) mmol/L,P=0.001].Logistic回归分析显示,糖尿病史(OR=4.162,95%CI 1.717~10.098,P=0.002)、较高收缩压(每增加1 mmHg,OR=1.028,95%CI 1.011~1.045,p=0.001)、降压药服用史(OR=3.141,95%CI 1.496~6.591,P=0.002)、糖尿病视网膜病变(OR=5.561,95%CI2.361~13.100,P<0.001)、较高糖化血红蛋白(每增加1%,OR=1.680,95%CI1.333~2.118,P<0.001)是DKD的相关因素,而血尿(OR=2.781,95%CI 1.334~5.798,P=0.006)和较高血红蛋白(每增加1g/L,OR=1.022,95%CI1.008~1.037,P=0.002)则为NDKD的相关因素.结论 DKD与NDKD之间的临床表现及病理类型存在差异,糖尿病病史、眼底检查、大量蛋白尿、降压药服用史、较高的糖化血红蛋白水平对DKD的诊断有较好的预测作用,而血尿和较高的血红蛋白水平对NDKD的诊断有一定指导意义.糖尿病合并慢性肾脏病患者行肾活检的指征需根据各临床表现综合分析.     

透析中心夜间血液透析治疗尿毒症患者的疗效及安全性

目的 观察透析中心夜间血液透析（INHD）治疗尿毒症患者的疗效和安全性。 方法 32例维持性血液透析（MHD）患者行INHD共6个月,3次/周,7.5 h/次。进入INHD前及开始后1、3、6（或3、6）个月测定透析相关指标,做心脏彩超检查、SF-36问卷调查,记录药物使用情况。 结果 进入INHD后,患者透前血压显著下降（130.3/86.0比139.3/88.6 mm Hg, P < 0.01）;透后血压显著上升（121.1/80.5比115.0/77.8 mm Hg,P < 0.01）;透析中高血压（9.8%比24.0%）及低血压发生率（7.3%比14.9%）均显著减少（均P < 0.01）。INHD 6个月后血磷[（1.37±0.27）比（2.08±0.49） mmol/L,P < 0.01]和iPTH值[（355.4±139.6）比（632.3±750.0） ng/L,P < 0.01]显著下降;血钙水平显著上升[（2.64±0.25）比（2.28±0.37） mmol/L,P < 0.05]。与INHD 1个月相比,INHD 6个月时高密度脂蛋白（HDL）显著升高[（1.27±0.29）比（0.75±0.08） mmol/L];低密度脂蛋白（LDL）显著下降[（2.04±0.52）比（2.75±0.75） mmol/L,P < 0.05];尿素下降率（URR）[（79.7±0.1）%比（64.7±4.7）%]和Kt/V（1.40±0.44比0.89±0.25,P < 0.01）显著增加;β2-MG水平显著下降[（17.3±3.9）比（24.6±5.9） mg/L,P < 0.01];左室质量指数（LVMI）显著下降（99.8±29.0比114.8±72.7,P < 0.05）;SF-36量表生理功能、生理职能和情感职能得分显著升高（均P < 0.01）。INHD 6个月时降压药物使用种类、EPO剂量、活性维生素D3（P < 0.05）及降磷药物剂量（P < 0.01）均显著减少,停用降压药、活性维生素D3及降磷药物患者数显著增加（P < 0.05）。 结论 INHD能改善高血压、贫血、钙磷代谢、脂质代谢紊乱,改善心功能,提高生活质量,不良反应少,具有很好的应用前景。     

儿童无症状尿检异常IgA肾病的临床病理和预后分析

目的 探讨儿童无症状尿检异常的IgA肾病的临床病理特征和预后。 方法 对54例IgA肾病儿童的临床和病理特征进行分析。根据起病时有无临床症状分为无症状尿检异常组和有症状肾炎组。组织病理学分级参照Lee氏和Katafuchi氏半定量积分法。 结果 无症状尿检异常组18例，有症状肾炎组36例。有症状肾炎组尿蛋白量（24 h）明显高于无症状尿检异常组[（2.3±2.2） g比（0.4±0.3） g，P < 0.05]。无症状尿检异常的IgA肾病儿童表现为镜下血尿者，87％有尿微量白蛋白增高。无症状尿检异常IgA肾病患儿病理表现以Lee 氏Ⅰ~Ⅱ级为主，2例表现为Lee氏Ⅳ~Ⅴ级和 5例发生Katafuchi Ⅱ~Ⅲ级肾小管间质病变。有症状肾炎组Lee氏病理分级以Ⅱ~Ⅲ级为主，两者病理分级分布差异无统计学意义（P > 0.05）。全组患儿平均随访（26.9±8.8）月后，1例病理为Lee 氏Ⅴ级患儿进入终末期肾衰竭，其余患儿Scr均无升高1倍以上。 结论 无症状尿检异常的儿童IgA肾病虽临床症状轻微，但可出现病理损害严重的病例，并影响其预后。     

Clinicopathological features and renal outcomes of IgA nephropathy with acute tubulointerstitial nephropathy

Objective To evaluate the clinicopathological characteristics and outcomes of IgA nephropathy (IgAN) with acute tubulointerstitial nephropathy (ATIN). Methods Patients who were diagnosed as IgAN with ATIN and IgAN without ATIN by renal biopsy in Peking University First Hospital were enrolled. There were 74 cases of IgAN with ATIN, and seventy-four cases of IgAN without ATIN were enrolled based on stratified sampling (chosen by 1∶1). The two groups were well matched with age, gender, follow-up time, mesangial hypercellularity(M), endocapillaryhypercellularity(E), segmental glomerulosclerosis(S), tubular atrophy/interstitial fibrosis(T) and cellular/fibrocellular crescent(C). The clinicopathological characteristics and outcomes of two groups were retrospectively analyzed. A composite end point, defined as 30% or 50% estimated glomerular filtration rate (eGFR) decline and end stage renal disease (ESRD) was used. Renal function and proteinuria during follow-up were observed. Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multivariate Cox regression models. Results Seventy-four cases of IgAN with ATIN and seventy-four cases of IgAN without ATIN were enrolled. Serum creatinine [(185.6±83.2) μmol/L vs (146.3±69.2) μmol/L, P=0.010] and incidence of acute kidney disease (AKD) (31.1% vs 5.4%, P＜0.001) were higher in IgAN with ATIN group than those in IgAN without ATIN group. Patients in ATIN group received more immunosuppressive treatment (86.5% vs 58.1%, P＜0.001). During 1 year after biopsy, mean eGFR increased significantly in IgAN with ATIN group [(39.7±14.6) ml?min-1?(1.73 m2)-1 vs (47.2±19.9) ml?min-1?(1.73 m2)-1, P=0.017], but mean eGFR was not statistic different in IgAN without ATIN group [(60.0±30.5) ml?min-1?(1.73 m2)-1 vs (59.0±31.7) ml?min-1?(1.73 m2)-1, P=0.567]. Median follow-up was 23.0 months in IgAN with ATIN group, and Median follow-up was 30.0 months in IgAN without ATIN group. Incidence of composite end point had no significant differences between two groups. IgAN with ATIN was not the independent risk factor for end point. IgAN patients with ATIN were divided into two groups (with AKD and without AKD), then renal survival rate was higher (Log-rank test, χ2=5.293, P=0.021) and the risk for composite end point decreased by 79.2% (HR=0.208, 95%CI 0.046-0.939, P=0.041) in the group with AKD. Conclusions In IgAN, there is a subgroup of patients with the specific pathological phenotype combined with ATIN. Compared with those without AKD, the risk for composite end point of IgAN patients with ATIN and AKD showed a 79.2% decrease.     

雷公藤甲素对IgA肾病患者外周血单个核细胞炎性反应及凋亡的影响

目的 探讨IgA肾病(IgAN)患者外周血单个核细胞（PBMC）炎性因子分泌及自身凋亡状态,以及雷公藤甲素(TP) 对其调节的相关机制。 方法 取IgAN患者（n=29）及健康人（n=16）外周血,分别通过酶联免疫吸附试验（ELISA）和硝酸还原酶法（Griess法）检测血浆肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和一氧化氮(NO)表达情况。体外培养IgAN患者PBMC,以不同浓度TP刺激PMBC,四唑盐比色间接法（MTT）检测TP对细胞生长的抑制效应。根据MTT结果,分别分为IgAN患者PBMC组、植物血球凝集素（PHA,10 mg/L,促细胞分裂原）模型组和PHA（10 mg/L）+TP（12.5 μg/L、25 μg/L）处理组。ELISA法检测上清液中TNF-α、IL-6的分泌情况;Griess法检测上清液中NO含量;流式细胞仪分析细胞凋亡率;RT-PCR法、Western印迹法检测PBMC中B细胞淋巴瘤/白血病-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、半胱天冬蛋白酶（caspase）-9、caspase-3基因和蛋白表达变化。 结果 IgAN患者血浆TNF-α[（131.57±50.61） ng/L比（30.24±18.93） ng/L,P < 0.01],IL-6[（76.36±25.21） ng/L比（35.08±16.59） ng/L,P < 0.01]和NO[（46.36±12.93） μmol/L比（26.61±10.87） μmol/L,P < 0.01]均显著高于健康人,PBMC凋亡率亦显著高于健康人[（16.88±5.66）%比（8.67±3.87）%,P < 0.01]。TP可抑制IgAN患者PBMC分泌 TNF-α、IL-6 和NO,诱导其凋亡;也可抑制Bcl-2表达,增加Bax、caspase-9、caspase-3表达。 结论 IgAN患者体内PBMC处于高度活化状态,并且凋亡率增高。TP能有效抑制IgAN患者PBMC的炎性活化状态,并可能通过线粒体途径改变Bcl-2蛋白家族抗凋亡因子和促凋亡因子平衡而诱导IgAN患者PBMC凋亡。     

Pregnancy in patients with IgA nephropathy: a retrospective study for 20 years

Objective To analyze prognosis of pregnancy and kidney disease, and evaluate effects of renal pathology on pregnant outcomes and clinical risk factors of adverse outcomes of pregnancy in IgA nephropathy (IgAN) patients. Methods IgAN patients with more than 20 weeks of pregnancy were included, by retrieving the medical database in Peking Union Medical College Hospital from January 1996 to December 2015. Their detailed information during hospitalization and follow-up was recorded, and outcomes of pregnancy and kidney diseases in IgAN patients were assessed. According to Lee's renal pathological grade system, patients were divided into gradeⅣ&Ⅴ group and below grade Ⅳ group to compare their pregnant prognosis. IgAN patients were divied into fetus survival group and fetus death group according to their pregnancy outcomes. The fetal survival factors were analyzed by single factor and multivariate regression. Results A total of 64 pregnancies in 62 patients were included with a mean age of (30.31±4.05) years. The fetus survival rate was 87.5% and the average gestational periods was (35.41±5.10) weeks (ranging from 20-40 weeks). The incidence of pregnancy-induced hypertension syndrome is 17.2% (11 cases). The preterm birth rate was 24.1% (14 cases) among the live births. Serum creatinine increased in 18 cases (28.1%) during pregnancy with median increment of 38.5 μmol/L, and 72.2% patients completely recovered to the level before pregnancy in the postpartum period of 6 months. The incidence of fetus death (38.1% vs 0.0%, P＜0.01), low birth weight infant (46.2% vs 11.1%, P＜0.05) and pregnancy-induced hypertension syndrome (33.3% vs 11.1%, P＜0.05) in Lee's grade Ⅳ&Ⅴ group was higher than those in below grade Ⅳ group. The serum creatinine, urine protein excretion, renal hypertension before pregnancy and renal segmental glomerular sclerosis were significantly increased in fetus death group as compared with those in fetus survival group (all P＜0.05). Logistic regression showed that in all patients an estimated glomerular filtration rate (eGFR)＜60 ml?min-1?(1.73 m2)-1 (OR=76.978, 95%CI 3.327-1780.939, P=0.007) and renal hypertension (OR=14.464,95%CI 1.245-168.053, P=0.033) before pregnancy were the independent risk factors for fetus death, while multipara was a protective factor (OR=0.063, 95%CI 0.005-0.876, P=0.040). Conclusions The fetus survival and kidney prognosis in IgAN patients are closely related to the severity of clinical and pathological changes before pregnancy. Reduced eGFR and complication of renal hypertension are the independent risk factors for adverse prognosis of pregnancy.     

胃转流手术治疗非肥胖型2型糖尿病180例疗效观察

目的探讨胃转流手术治疗2型糖尿病(T2DM)的疗效。方法回顾性分析2012年5月至2014年5月收治的180例接受胃转流手术(RYGB)的非肥胖型T2DM患者临床资料,根据疗效判定标准分为2组,临床完全缓解组(133例)和临床部分缓解组(45例)。应用SPSS17.0软件分析临床缓解情况、术前术后12个月的糖代谢功能指标及体重指数,采用t检验,P0.05为差异有统计学意义。结果术后12个月,临床完全缓解率73.9%(133/180),临床部分缓解率25.0%(45/180),无效率1.1%(2/180),总有效率98.9%(178/180)。临床完全缓解组与临床部分缓解组比,患者的年龄更小[(48.7±3.1)岁比(60.1±4.2)岁,t=6.91,P0.05)],病程更短[(6.8±1.8)年比(12.8±3.2)年,t=7.21,P0.05)],空腹C肽值更高[(1.49±0.82)nmol/L比(0.74±0.31)nmol/L,t=4.18,P0.05)],空腹血糖值更低[(8.17±2.31)mmol/L比(12.21±2.41)mmol/L,t=5.17,P0.05)],差异均有统计学意义。而体重和性别,术前术后差异无统计学意义(P0.05)。结论 RYGB手术治疗2型糖尿病安全有效,治疗效果不依赖于体重下降。     

PTGBD联合LC对高龄急性胆囊炎合并糖尿病的疗效分析

目的 探讨经皮经肝胆囊穿刺引流(PTGBD)联合腹腔镜胆囊切除术(LC)对高龄急性胆囊炎合并糖尿病患者的疗效。方法 本回顾性研究以44例高龄急性胆囊炎合并糖尿病患者为研究对象,根据LC术前接受的治疗情况不同分为研究组(PTGBD组,n=20)和对照组(保守治疗组,n=24)。比较两组患者术中、术后各项指标的变化情况和并发症发生率。结果 研究组平均手术时间[(52.78±6.65)min vs(72.56±10.63)min]、术中出血量[(12.10±2.77)mL vs (18.52±2.47)mL]和术后住院时间[(5.85±0.75)d vs (8.91±1.09)d]均少于对照组(P<0.05),研究组首次排气时间[(20.33±2.99)h vs (28.27±4.38)h]及早期下床活动时间[(28.66±3.29)h vs (39.31±4.33)h]均早于对照组(P<0.05)。两组患者术后1 d的WBC、CRP、VAS评分差异没有统计学意义,但术后3 d两组WBC[(5.84±1.01)×10⁹/L vs (6.72±0.67)×10...     

高孕激素状态下促排卵方案用于卵巢正常反应患者IVF-ET的自身对照研究

目的探讨第一周期采用降调节长方案行体外受精/卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)未获成功的卵巢正常反应患者,改用高孕激素状态下促排卵(PPOS)方案的临床效果。方法回顾性分析2014年1月至2015年11月我科第一周期长方案促排卵后助孕治疗未获成功,第二周期PPOS方案后行冻融胚胎移植(FET)的卵巢正常反应患者共42例,自身对照两种促排卵方案中激素水平、药物使用、获卵及胚胎情况以及PPOS方案后FET的妊娠结局。结果PPOS方案中Gn天数[(10.33±2.00)d]、Gn总量[(2 325.00±449.08)U]显著低于长方案[分别为(13.00±2.27)d、(3 182.98±904.91)U](P0.05);PPOS方案扳机日血清LH水平[(1.64±1.31)U/L]显著高于长方案[((0.91±1.01)U/L]、孕酮(P)水平[(2.25±0.86)nmol/L]显著低于长方案[(3.87±1.68)nmol/L](P均0.05);PPOS方案的平均获卵数、成熟卵母细胞数、正常受精数、可利用胚胎数与长方案比较无显著性差异(P0.05),正常受精率[(71.82±17.64)%]、优胚数[(3.62±1.97)枚]和优胚率[(62.21±24.04)%]均显著高于长方案[分别为(63.75±15.77)%、(2.79±1.65)枚、(48.48±22.53)%](P0.05)。PPOS方案中有3例患者因无冷冻胚胎取消周期;39例患者行FET(共46个周期),22个周期获得临床妊娠,周期临床妊娠率47.83%,种植率24.74%,显著高于长方案[分别为7.02%、3.64%](P0.05)。结论对于长方案促排后助孕未获成功的卵巢正常反应患者,PPOS方案可获得较好的临床妊娠结局,为促排卵治疗提供了一种新的选择方案。     

Transformation of DNA demethylation in the regulatory region of TGFB1 gene in patients with diabetic nephropathy

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 diagnosed as diabetes mellitus were selected, including 42 patients with diabetes mellitus (DM group) and 49 with diabetic nephropathy (DN group). Thirty cases with health examination were selected as healthy control group (Con group). DNA was extracted from all the subjects' peripheral blood and modified by sodium bisulfite. DNA methylation status of TGFB1 gene regulatory region was screened by methylation specific PCR and the DNA methylation level was detected by bisulfite sequencing PCR. ELISA was used to test serum TGF-β1. Blood urea nitrogen, creatinine, fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin and urinary albumin to creatinine ratio (UACR) were detected by automatic biochemistry analyzer. Pearson correlation analysis and multiple stepwise regression were used to analysis TGF-β1-related factors, the correlation between the level of serum TGF-β1 and the pathological grade was analyzed in DN patients. Results There were 12.2% patients in DN group with DNA methylation of TGFB1 gene regulation region, lower than those in DM group (42.8%) with Con group (73.3%) (all P＜0.05). The methylation level of TGFB1 regulatory region was 12.5%±8.1% in DN group, significantly lower than those in DM group (35.6%±6.0%) and Con group (66.7%±9.1%) (all P＜0.05). Moreover, compared with that in DM group (1367.22±126.13 ng/L) and Con group [(296.38±74.37) ng/L], TGF-β1 expression was increased significantly in DN group [(2885.73±411.36 ng/L] (all P＜0.01). In DN patients serum TGF-β1 was correlated with eGFR (β=-0.690, P＜0.01) and the methylation (β=-0.302, P＜0.01), and the serum TGF-β1 was negatively correlated with DNA methylation level (r=-0.925, P＜0.01), but positively correlated with the pathological scores among glomerulus, tubulus and arterioles (rs=0.847, P＜0.01). Meanwhile the methylation level related to the pathological grade (χ2=23.667, P=0.04). Conclusion Demethylation in the regulatory region of TGFB1 may play an important role in the activation of TGFB1 induced by high glucose in mesangial cells, so as to participate in the occurrence and development of DN.     

调节性及辅助性T细胞在人类IgA肾病中的表达及意义

目的 探讨CD4+CD25high调节性T细胞（Treg）及辅助性T细胞亚群（Th1、Th2）比例失衡在IgA肾病（IgAN）免疫发病机制中的作用。 方法 用流式细胞仪检测IgAN患者外周血Treg及Th1、Th2的比例。以胞内染色技术检测叉头框蛋白3（FOXP3）的表达。Treg及Th1、Th2的比例与IgAN各项临床病理指标的相关性分析采用Spearman或Pearson相关分析法。 结果 IgAN患者外周血中Treg比例明显高于健康人[（2.14±0.82）％比（1.59±0.53）％，P ＜ 0.05]，与血IgA水平呈正相关（r = 0.397，P ＜ 0.05），与eGFR呈负相关（r = -0.376，P ＜ 0.05）。IgAN患者外周血中Th2细胞比例显著高于健康对照组[（2.57±0.72）％比（1.81±1.10）％，P ＜ 0.05]，与血IgA水平呈正相关（r = 0.468，P ＜ 0.05）。IgAN患者Th1/Th2比值显著低于健康对照组（5.75±1.89比12.73±9.79，P ＜ 0.05），但与临床各指标间没有相关性。 结论 IgAN患者体内存在T细胞亚群表达紊乱。Treg在外周血中的增多以及以Th2为优势的Th1/Th2失衡可能在IgAN的发病中起重要作用。     

小肠旷置术对2型糖尿病大鼠糖耐量的影响

目的 观察不同肠段小肠旷置术对2型糖尿病大鼠血糖和糖耐量的影响.方法 将40只Goto-Kakizaki(GK)大鼠随机分为旷置十二指肠组(A组)、旷置十二指肠和近端空肠组(B组)、旷置十二指肠和全部空肠组(C组)、旷置次全小肠组(D组)和假手术组(SO组)5组,每组8只.测定各组大鼠术前及术后1、3、6、12、24周空腹血糖;用葡萄糖3 g/kg灌胃,测定各组大鼠术前及术后1、24周口服葡萄糖后0、30、60、120和180 min耐糖血糖值,描制血糖值随时间变化曲线,计算糖耐量曲线下面积.结果 与术前比较,各旷置组术后各时间点空腹血糖、糖耐量血糖峰值和糖耐量曲线下面积均明显减少(B组术前和术后1周空腹血糖分别为(9.0±2.4)mmoL/L和(4.4±1.0)mmol/L、糖耐最血糖峰值和糖耐量曲线下面积分别为(20.8±3.1)mmol/L和(10.3±2.0)mmol/L、(2658±417)mmol·min/L和(1324±317)mmol·min/L,P＜0.05或P＜0.01);SO组空腹血糖在术后1、3、6周未发生明显变化(P＞0.05),术后12周(9.1±2.4)mmol/L、24周(10.0±2.3)mmol/L显著高于术前(8.1±1.9)mmol/L,P＜0.01);与术前比较,SO组糖耐量血糖峰值和糖耐量曲线下面积在术后1周未发现明显变化(P＞0.05),术后24周糖耐量血糖峰时后移、峰值增高(25.6±2.0)mmol/L比(21.4±2.7)mmol/L,糖耐量曲线下面积明显增加(3422±360)mmol·min/L比(2667±377)mmol·min/L,P＜0.01.与SO组比较,各旷置组术后各时间点空腹血糖、糖耐最血糖峰值和糖耐量曲线下面积均较SO组显著下降(P＜0.05或P＜0.01).各旷置组之间比较,B组术后各时间点空腹血糖、糖耐最血糖峰值和糖耐量曲线下面积均显著低于A组[术后24周B组和A组空腹血糖分别为(4.6±1.2)mmol/L和(6.2±1.5)mmoL/L、糖耐量血糖峰值分别为(9.7±2.2)mmol/L和(12.4±1.7)mmoL/L、糖耐量曲线下面积分别为(1230±293)mmol·min/L和(1599±264)mmol·min/L,P＜0.05或P＜0.01],对血糖控制和糖耐量改善效果优于A组,但与C组和D组相比差异均无统计学意义(P＞0.05).结论 小肠旷置术可控制2型糖尿病大鼠的血糖并改善糖耐量,其中旷置十二指肠和近端空肠是临床可行的术式.     

The status on achieving Kt/Vurea target and its relation with residual renal function and clinical characteristics of peritoneal dialysis patients

ObjectiveTo explore the present status on achieving Kt/Vurea target in Chinese peritoneal dialysis (PD) patients and its relation with residual renal function (RRF) and clinical characteristics. Methods This was a cross-sectional study carried out in 5 PD centers in different area of China. Totally 681 clinical stable PD patients with duration≥3 months who completed dialysis adequacy and biochemical test during April 1st, 2011 and August 31st, 2011 were enrolled in this study. The demographic data and clinical characteristics were compared according to varied Kt/Vurea and RRF levels. Results (1)The total Kt/Vurea was 1.95±0.59,and total Ccr was （63.80±30.84）L·week-1·(1.73 m2) -1 for the whole group, there were 67.4% subjects achieving the Kt/Vurea target. (2) Patients achieving Kt/Vurea targetwere prone to be female and had smaller size with higher RRF and urine volume (P＜0.05). The serum calcium and phosphorus were controlled well in these patients (P＜0.05). They also had better higher cholesterol and low-density lipoprotein, and lower CRP level and less complications (P＜0.05). (3)Serum albumin was higher but inflammation and complications were less in patients with Kt/Vurea value≥1.7 and RRF≥2 ml·min-1·（1.73 m2）-1 (subgroup 1), as compared to those with Kt/Vurea≥1.7 but RRF＜2 ml·min-1·（1.73 m2）-1 (subgroup 2) and those with Kt/Vurea＜1.7(subgroup 3) (P＜0.05). The subgroup 2 and 3 were statistically different in these clinical indices, serum calcium [(2.22±0.21) mmol/L vs (2.14±0.24) mmol/L, P＜0.01], serum phosphorous [(1.43±0.47) mmol/L vs (1.66±0.52) mmol/L, P＜0.01], cholesterol [(4.91±1.29) mmol/L vs (4.62±0.99) mmol/L, P＜0.05], low-density lipoprotein [(2.86±0.96) mmol/L vs (1.13±0.61) mmol/L, P＜0.01], high-density lipoprotein [(1.08±0.33) mmol/L vs (2.20±0.72) mmol/L, P＜0.01]. (4)The Kt/Vurea was positively correlated with RRF (R2＝0.317); if RRF decreased 1 ml/min, the hazard of Kt/Vurea un-targeting increased 40.3%. Conclusions About 67.4% of PD patients can reach the Kt/Vurea target recommended by K/DOQI. RRF makes a great contribution to Kt/Vurea target. The clinical characteristics are poorer in patients who can not achieve the Kt/Vurea target, or with worse RRF.     

Role of OMA1 in lipopolysaccharide-induced acute kidney injury

Objective To investigate the role of OMA1 in acute kidney injury (AKI) induced by lipopolysaccharide (LPS). Methods OMA1 wild-type and knocked out mice (8 week old) were injected with 10 mg/kg body weight of LPS. The model was confirmed by testing mouse serum creatinine and blood urea nitrogen. The apoptosis in mouse kidney cortex was examined by TUNEL staining and cleaved caspase 3. In vitro, in humam kidney proximal tubular cells (HK2) were knocked down OMA1 by transfecting OMA1 shRNA, with the scramble shRNA being used as negative control of transfection. HK2 cells were cultured with 5 μg/ml of LPS for 24 hours to induce apoptosis. DAPI staining of cells and caspase-3 activity were applied to test apoptosis. The images of mitochondria in cells were obtained by transfection of mito-green plasmid and OMA1 shRNA. Western blotting was used to exam the OMA1 and Cytochrome C expressions. Results Compared with OMA1 KO mice, LPS induced more severe AKI of WT mice with higher Scr [(97.2±26.5) μmol/L vs (53.0±17.7) μmol/L, P＜0.05] and BUN [(43.3±13.7) mmol/L vs (29.7±7.7) mmol/L, P＜0.05]. Moreover, there were more apoptosis cells in kidney cortex in WT mice than in OMA1 KO mice [(75.4± 26.1)/mm2 vs (38.3± 14.4)/mm2, P＜0.05]. About 46% of OMA1 expressions in HK2 cells were inhibited by OMA1 shRNA transfection (P＜0.05). Further, OMA1 shRNA cells with LPS stimulation had decreased mitochondria fragmentation [(29.8±10.9)% vs (43.2±6.8)% , P＜0.05], Cytochrome C release [(37.0±12.3)% vs (76.0±26.2)%, P＜0.05], and cell apoptosis [(13.2±3.9)% vs (25.0±7.1)%, P＜0.05] as compared with control cells. Conclusion Knockdown of OMA1 alleviated septic AKI through inhibition of cell apoptosis, mitochondria fragmentation, and Cytochrome C release.     

Clinicopathological and prognostic analysis of IgA nephropathy patients with anemia

Objective To analyze the clinicopathological features of IgA nephropathy (IgAN) patients with anemia and the influencing factors of prognosis. Methods The clinical and pathological data of patients diagnosed with primary IgAN at the First Affiliated Hospital of Fujian Medical University from January 1, 2006 to December 31, 2016 were retrospectively analyzed. The patients were divided into anemia group and non-anemia group according to whether the patient was anemia or not. The clinical and pathological data of the two groups were collected. All of them were followed up from the date of renal biopsy to January 1, 2018. Survival curves of the two groups were drawn by Kaplan-Meier method, and compared by Log-rank test. Multivariate Cox proportional hazards regression model was adopted to explore the influencing factors of prognosis in IgAN patients. Results A total of 231 subjects were enrolled, including 122 males (52.8%), and the male-female ratio was 1.12∶1. Their age was (34.8±10.1) years (15-68 years). There were 70 patients (30.3%) in anemia group, 161 cases (69.7%) in non-anemic group. Compared with non-anemia group, anemia group had higher proportion of females, lower serum albumin, higher proportion of tubular atrophy/interstitial fibrosis (T1/2), endothelial cell proliferation (E1) and crescent formation (C1/2), which were statistically significant (all P＜0.05). The patients had a median follow-up time as 6.3 years (0.3-12.9 years). Survival analysis showed that patients in anemia group had lower cumulative renal survival rate than that in non-anemia group ( χ2=15.234, P＜0.001). Multivariate Cox hazards regression analysis revealed that anemia (HR=3.820, 95%CI 1.674-8.719, P=0.001), tubular atrophy/interstitial fibrosis (T1/2) (HR=3.770, 95%CI 1.026-13.852, P=0.046), glomerular segmental sclerosis/adhesion (S1) (HR=4.211, 95%CI 1.139-15.576, P=0.031), hypertension (HR=2.988, 95%CI 1.276-6.999, P=0.012), increased 24 h urinary protein (HR=1.103, 95%CI 1.046-1.163, P＜0.001) and estimated glomerular filtration (eGFR)＜60 ml?min-1?(1.73 m2)-1 (HR=3.725, 95%CI 1.639-8.462, P=0.002) were the independent risk factors for poor renal prognosis in patients with IgAN. Conclusions The clinicopathological features of IgAN patients with anemia are relatively serious, and the renal cumulative survival rate is lower. Anemia, tubular atrophy/interstitial fibrosis (T1/2), glomerular segmental sclerosis/adhesion (S1), hypertension, increased urinary protein and eGFR＜60 ml?min-1?(1.73 m2)-1 are the independent risk factors for poor renal prognosis in patients with IgAN.     

缬沙坦与贝那普利联用治疗移植肾慢性损伤的远期效果

目的 探讨血管紧张素受体拮抗剂缬沙坦与血管紧张素转化酶抑制剂贝那普利联合应用治疗肾移植患者移植肾慢性损伤的远期效果. 方法非糖尿病患者肾移植术后尿蛋白＞0.5g/d或SCr＞177 mmol/L(＞2 mg/d)32例,随机分2组:①治疗组23例.男9例,女14例.平均40岁.病理诊断慢性移植物肾病(CAN)13例、环孢素中毒3例、肾小球疾病7例.②对照组9例.男4例,女5例.平均35岁.CAN 6例、环孢素中毒1例、肾小球疾病2例.治疗组给予缬沙坦(80mg/d)与贝那普利(20 mg,2次/d)联合治疗3年,对照组未进行此项处理.比较2组患者治疗前后SCr、24 h尿蛋白变化及移植肾生存时间.结果 随访3年后,治疗组SCr为(252.2±117.9)mmol/L,对照组为(375.3±203.0)mmol/L,2组比较差异有统计学意义(P＜0.05).治疗组CAN患者SCr为(282.4±147.3)mmol/L,对照组为(528.7±107.8)mmol/L,2组比较差异有统计学意义(P＜0.01).治疗组24 h尿蛋白为(1.0±0.6)g,对照组为(1.3±0.7)g,组问差异无统计学意义(P＞0.05).移植肾存活时间治疗组76个月,对照组为71个月,组间差异无统计学意义(P＞0.05).结论 缬沙坦与贝那普利联合应用可保护移植肾功能,对蛋白尿及移植肾远期存活的影响有待进一步观察.     

细胞因子信号传导抑制蛋白1抑制高糖诱导的肾小球系膜细胞单核细胞趋化蛋白1的表达

目的 探讨细胞因子信号传导抑制蛋白1(SOCS-1)对高糖状态下肾小球系膜细胞单核细胞趋化蛋白1（MCP-1）表达的影响。 方法 体外培养人肾小球系膜细胞,应用脂质体2000分别转染pCR3.1-SOCS-1表达质粒和pCR3.1 空质粒载体,G418筛选阳性克隆。分别采用低糖（5.5 mmol/L）、高糖（30 mmol/L）、低糖+甘露醇（24.5 mmol/L甘露醇）和JAK-STAT信号通路抑制剂AG490 （10 μmol/L）进行刺激。Western印迹检测系膜细胞SOCS-1、信号转导和转录活化因子1、3（STAT1、STAT3）及其磷酸化蛋白（p-STAT1、p-STAT3）的表达。ELISA法和放免法测定细胞上清液中MCP-1、FN和Ⅳ型胶原的含量。RT-PCR法检测SOCS-1和MCP-1 mRNA的表达。 结果 高糖刺激系膜细胞SOCS-1蛋白和mRNA表达呈时间依赖性变化, 4 h表达达到峰值,然后逐渐减低,24 h达基线水平。与低糖组相比,高糖组系膜细胞STAT1和STAT3磷酸化水平显著上调（P < 0.01）; MCP-1 mRNA水平表达显著上调[（0.39±0.05）比（0.16±0.02）,P < 0.01];上清液中MCP-1[（459±67）比（241±19） ng/L]、FN[（5.84±0.61）比（3.41±0.31） mg/L]和Ⅳ型胶原[（16.45±2.30）比（9.56±1.52） μg/L] 含量均显著增加（均P < 0.01）。与空载体对照组相比,SOCS-1过表达组系膜细胞STAT1和STAT3的磷酸化水平显著下降（P < 0.05）;MCP-1 mRNA表达下调[（0.34±0.04）比（0.42±0.05）,P < 0.05]; 上清液中MCP-1[(387±47）比（463±56） ng/L]、 FN[（4.61±0.57）比（5.76±0.74） mg/L]和Ⅳ型胶原[(13.4±2.32)比（17.1±2.57） μg/L] 含量显著减少（均P < 0.05）。与高糖组相比,AG490组系膜细胞MCP-1 mRNA（0.31±0.04）表达显著下调;上清液中MCP-1[（361±53） ng/L]、FN[（5.46±0.71）mg/L]和Ⅳ型胶原[（15.2±1.97） μg/L]含量均减少。 结论 SOCS-1过表达抑制高糖状态下肾小球系膜细胞MCP-1及细胞外基质的分泌可能部分是通过影响STAT1和STAT3的激活而实现。     

Association between obesity and absolute renal risk factors in patients with IgA nephropathy

Objective To investigate the influence of obesity on renal lesion in IgA nephropathy (IgAN) patients by analyzing the association between obesity and absolute renal risk factors (ARR). Method Clinical-pathological data of IgAN patients diagnosed by renal biopsy in General Hospital of Ningxia Medical University were collected retrospectively. According to the body mass index (BMI), patients were divided into non-obese group (BMI＜28, N-OB group) and obese group (BMI≥28, OB group). Their clinical characteristics, pathological index and ARR scores were compared. The relationship of BMI and ARR was analyzed by ordinal logistic regression models. Results (1) A total of 674 IgAN patients with mean age of 35.5±11.3 years were enrolled, including 94 in OB group and 580 in N-OB group respectively. Compared with those in the N-OB group, the proportion of male, age, mean arterial pressure, blood uric acid, blood triglyceride, diabetes mellitus and hypertension increased in OB group (all P＜0.01). Patients in OB group had lower estimated glomerular filtration rate (eGFR) and higher ARR score than those in N-OB group (all P＜0.05). (2) More severe thickening renal small artery wall and hyaline degeneration were observed in the OB group than in the N-OB group (all P＜0.01). There was no statistical difference between the two groups in Lee classification, Oxford classification, mesangial cell proliferation, glomerular sclerosis, crescent formation, renal tubular atrophy, interstitial inflammatory cell in filtration and endothelial cell proliferation. (3) After adjusting for age, sex, blood uric acid, serum albumin, eGFR, low density lipoprotein, glomerular sclerosis, interstitial inflammatory cell infiltration, renal tubular atrophy and vascular wall thickening, BMI was still an independent risk factors for ARR in IgAN patients (OR=1.09, 95%CI 1.03-1.14). Conclusions BMI is an independent risk factors for ARR in IgAN patients. Early prevention and control of obesity and its associated risk factors may improve outcomes of IgAN patients.     

线粒体ATP敏感性钾通道阻断剂对在体大鼠肺缺血后处理的作用及其机制

目的 探讨缺血后处理(IPO)对大鼠在体肺缺血-再灌注损伤(I/R)的保护作用及线粒体ATP敏感性钾通道(mitoKATP)在缺血后处理效应中的作用.方法 将Wistar大鼠35只随机分为5组:假手术组(Sham组)、缺血再灌注损伤组(I/R组)、缺血后处理组(IPO组)、缺血再灌注损伤+5-羟基葵酸盐组(I/R+5-HD组)、缺血后处理+5-羟基葵酸盐组(IPO+5-HD组).观察各组肺组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、湿/干比值(W/D)以及病理形态学改变.结果 I/R组与Sham组比较MDA含量增加[(5.07±1.60)nmol/mg prot比(1.43±0.41)nmol/mgprot,P＜0.01],SOD活性减低[(12.38±2.24)U/mg prot比(45.51±5.42)U/mg prot,P＜0.01],W/D比值增高(5.45±0.82比3.05±0.47,P＜0.01),肺组织形态及超微结构明显受损;IPO+5-HD组与IPO组比较MDA含量增加[(3.74±0.71)nmol/mg prot比(2.60±0.43)nmol/mg prot,P＜0.01],SOD活性减低[(22.91±2.71)U/mg prot比(28.74±2.03)U/mg prot,P＜0.01],W/D比值增高(4.64±0.79比3.89±0.60,P＜0.01),肺组织形态及超微结构明显受损;IPO组与I/R组比较,肺组织MDA含量减少[(2.60±0.43)nmol/mg prot比(5.07±1.60)nmol/mg prot,P＜0.01],SOD活性增高[(28.74±2.03)U/mg prot比(12.38±2.24)U/mg prot,P＜0.01],W/D比值减低(3.89±0.60比5.45±0.82,P＜0.01),肺组织病理形态学改变轻于I/R组;I/R+5-HD组与I/R组比较,肺组织MDA含量[(5.14±1.30)mol/mg prot比(5.07±1.60)mol/mg prot,P＞0.05)、SOD活性[(11.65±1.82)U/mg prot比(12.38±2.24)U/mg prot,P＞0.05]、W/D比变化(5.54±0.61比5.45±0.82),差异无统计学意义(P＞0.05),肺组织病理形态学改变无明显差异.IPO+5-HD组的各项指标介于IPO组和I/R组之间.结论 缺血后处理能减轻大鼠在体肺缺血再灌注损伤,mitoKATP参与了肺缺血后处理效应.

Abstract：

Objective To investigate the protective effect of ischemic postconditioning (IPO) on lung ischemic reperfusion (L/R) in rats in vivo and the mechanism of mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker in the ischemic postconditioning. Methods Thirty five Wistar rats were randomly divided into 5 groups: sham group, I/R group, ischemic postconditioning (IPO) group, I/R +5-hydroxydecanoate (I/R + 5-HD) group, IPO + 5-HD group. The concentration of malondialdehyde (MDA) and activity of superoide dismutase (SOD) were determined in the lung homogenate, wet to dry weight ratio (W/D) was measured and pathological changes were also observed. Results The levels of MDA[(5.07±1.60) vs (1.43 ±0.41) nmol/mg prot,P＜0. 01]and W/D (5.45 ±0.82 vs 3.05 ±0. 47,P ＜0. 01 ) were increased significantly in I/R group as compared with sham group, while the activity of SOD[( 12. 38 ±2. 24) vs (45.51 ±5.42) U/mg prot,P ＜0. 01]was decreased, and the injury of lung tissues was significantly aggravated in IPO + 5-HD group as compared with IPO group[MDA: (3.74 ±0. 71 ) nmol/mg prot vs (2. 60 ± 0. 43 ) nmol/mg prot , P ＜ 0. 01]; W/D: 4. 64 ± 0. 79 vs 3. 89 ± 0. 60,P＜0.01; SOD:[(22.91 ±2.71) U/mg prot vs (28.74±2.03) U/mg prot,P＜0. 01]. The levels of MDA[(2.60±0.43) vs (5.07 ±1.60) nmol/mg prot,P＜0. 01]and W/D (3.89 ±0.60 vs 5.45 ±0. 82,P ＜0. 01 ) were decreased significantly in IPO group as compared with I/R group, the activity of SOD[(28.74±2.03) vs (12.38 ±2.24) U/mg prot,P＜0. 01]increased and lung tissue histological damage attenuated. The difference in MDA[(5.14 ± 1.30) vs (5.07 ± 1.60) nmol/mg prot, P ＞ 0. 05],W/D (5.54±0.61 vs5.45 ±0.82,P＞0.05) and SOD[(11.65 ±1.82) vs (12.38 ±2.24) U/mgprot,P ＞ 0. 05]levels had no statistical significance between I/R + 5-HD group and I/R group, and the injury of lung tissues had no significant difference too. Each index in IPO + 5-HD group was between IPO and I/R groups. Conclusion Ischemic postconditioning can attenuate the lung I/R injury, and mitoKATP plays a vital role in the protective procession of ischemic postconditioning on lung ischemic reperfusion.     

慢性肾脏病患者骨代谢与尿蛋白量的关系

目的 研究慢性肾脏病（CKD）患者骨代谢状况与尿蛋白量的关系。 方法 随机挑选2008年1月至2009年5月在本院肾活检证实为原发性肾小球疾病的CKD患者71例为对象。按尿蛋白量分为3组：A组25例,尿蛋白量<1.0 g/24 h;B组16例,尿蛋白量 （1.0~<3.5） g/24 h;C组30例,尿蛋白量≥3.5 g/24 h。健康体检者58例为健康对照组。常规测定血清白蛋白、24 h尿蛋白量及血清钙、磷、PTH、25羟基维生素D3[25-(OH)D3]、骨钙素（BGP）、I型胶原吡啶交联C终端肽（CTx）及尿钙/肌酐（UCa/Cr）等骨代谢指标。双能X线骨密度仪检测患者骨密度（BMD）。对各因素间进行Pearson相关分析。 结果 与健康对照组比较,A、B、C组CKD患者血钙分别为（2.23±0.08）、（2.13±0.09）、（2.04±0.06）比 （2.37±0.12） mmol/L;血25-（OH）D3分别为（50.19±6.58）、（47.78±6.69）、（42.42±10.85）比（56.34±8.34） nmol/L（均P < 0.05）;而UCa/Cr显著升高,分别为0.25±0.11、0.34±0.13、0.41±0.05比0.14±0.06（均P < 0.05）。B、C组血BGP分别为（18.69±7.35）、（16.13±5.76） μg/L,显著低于健康对照组的（22.88±6.21） μg/L;血CTx分别为（413.59±114.93）、（516.21±314.25） ng/L,显著高于健康对照组的（304.53±234.15） ng/L（均P < 0.05）。A、B两组BMD与健康对照组差异无统计学意义;C组BMD显著低于健康对照组[（1.028±0.090）比（1.090±0.062） g/cm2,P < 0.05]。Pearson相关分析显示,24 h尿蛋白量与血钙、血 25-(OH)D3呈负相关,与UCa/Cr 呈正相关;UCa/Cr与血CTx 呈正相关,与血BGP呈负相关;25-(OH)D3与BGP呈正相关,与CTx呈负相关。 结论 原发性肾小球疾病CKD患者的骨代谢异常主要表现为骨形成降低,骨吸收增加,其变化与蛋白尿程度相关,而大量尿蛋白患者骨代谢显著异常。