慢性肾脏病患者肾组织Klotho基因启动子的超甲基化与临床病理的相关性

目的 评价慢性肾脏病(CKD)患者肾组织和外周血单个核细胞(PBMC)Klotho基因启动子的甲基化水平,探讨Klotho基因启动子超甲基化与CKD患者临床病理特征的关系.方法 以47例接受肾脏活组织病理检查的CKD患者为研究对象,47例肾癌根治术患者肾脏切除标本中的正常肾脏组织和48例健康志愿者的PBMC分别作为肾组织和PBMC的对照组.采用焦磷酸测序(PS)法检测肾组织和PBMC Klotho基因启动子的甲基化水平.结果 CKD患者肾组织Klotho基因启动子甲基化率显著高于对照组,差异有统计学意义[(17.04±6.42)％比(9.34±2.43)％,P＜ 0.01];PBMC Klotho基因启动子甲基化率亦显著高于对照组,差异有统计学意义[(14.19±5.86)％比(6.90±2.39)％,P＜ 0.01].CKD患者PBMC与肾组织Klotho基因启动子甲基化率呈正相关(r=0.811,P＜0.01),PBMC Klotho基因启动子甲基化率预测肾组织Klotho基因启动子超甲基化的受试者工作曲线下面积为0.958(P＜0.01).肾组织和PBMC Klotho基因启动子甲基化率与eGFR均呈负相关(分别r=-0.827,P＜0.01;r=-0.626,P＜0.01),与肾小管间质纤维化面积呈正相关(r=0.865,P＜0.01;r=0.748,P＜0.01),与24 h尿蛋白量无相关.结论 CKD患者肾组织和PBMC Klotho基因启动子甲基化率升高,PBMC Klotho基因启动子甲基化率可作为肾组织Klotho基因启动子超甲基化的无创评价指标.Klotho基因启动子超甲基化与肾脏纤维化的关系值得进一步研究.     

胰岛素治疗对2型糖尿病肾病血清C反应蛋白水平的影响

目的:比较2型糖尿病(无肾病)及糖尿病肾病(DN)患者血清C反应蛋白(CRP)的水平,观察应用胰岛素治疗后血清CRP水平的变化。方法:2型糖尿病患者共100例,其中糖尿病(无肾病)为DM组40例,糖尿病肾病组为DN组60例。将DN组患者随机分组,口服糖适平组为DN1、胰岛素治疗组为DN2共治疗12周。选取正常对照组(NC)30例,应用化学发光法测定血CRP水平。结果:NC、DM组、DN组血清CRP水平分别为(2.90±1.8)mg/L、(5.8±3.2)mg/L、(9.2±5.6)mg/L逐渐升高,血清CRP水平与总胆固醇(TC)(r=0.510,P<0.01)、空腹血糖(FBG)(r=0.29,P<0.01)呈正相关。血清CRP在DN2组胰岛素治疗前后分别为(9.30±3.78)mg/L、(4.78±2.11)mg/L下降明显,有统计学差异(P<0.01);DN1组糖适平治疗前后(9.04±4.9)mg/L、(8.30±1.8)mg/L下降,无统计学差异(P>0.05)。结论:2型DM(无肾病)及DN组血清CRP水平逐渐升高,且DN经胰岛素治疗后血清CRP水平明显下降。     

2型糖尿病伴微量白蛋白尿患者尿酸与内皮功能紊乱的关系探讨

目的对比研究有无微量白蛋白尿的2型糖尿病患者尿酸与内皮功能紊乱的关系。方法采用横断面调查研究,于2010年3月—2011年5月在南方医科大学3所附属医院(南方医院、江都医院、珠江医院)招募无大血管疾病的2型糖尿病患者共149例,根据24h尿微量白蛋白是否≥30 mg将患者分为两组,其中112例患者24h尿蛋白30 mg为糖尿病肾病(DN)(-)组,37例患者尿白蛋白在30～300 mg为DN(+)组,同时招募49例年龄、性别相匹配的健康人群为对照组,分析一般人口学指标、生化指标与内皮功能紊乱指标;可溶性血管细胞间黏附分子1(sVCAM-1)的关系。结果DN(+)组尿酸高于其余两组[DN(+)vs DN(-)vs正常人=(370.3±116.1)μmol/L vs (334.2±100.0μmol/L)vs(324.5±63.7)μmol/L,P=0.083],DN(+)组sVCAM-1显著高于另外两组[DN(+)vs DN(-)vs正常人=(519.4±130.9)ng/ml vs(466.2±108.7)ng/ml vs(435.5±70.3)ng/ml,P=0.002]。通过多元回归分析发现,血尿酸在DN(+)组是sVCAM-1唯一独立的正相关因素(β=0.35,P=0.044),而在DN(-)组二者无显著相关性(β=0.052,P=0.593)。结论伴微量白蛋白尿的2型糖尿病患者,血尿酸较正常人显著升高,且与患者内皮功能紊乱呈显著正相关,而在无微量白蛋白尿的2型糖尿病患者这种关系并不显著,提示在出现微量白蛋白尿的2型患者需要更加严格控制尿酸水平。     

父源印记基因H19印记控制区域DNA甲基化与少、弱精子症相关性分析

目的:研究印记基因H19印记控制区域的DNA甲基化程度与男性少、弱精子症的相关性。方法:通过染色体核型分析和Y染色体微缺失检测排除染色体因素干扰,进一步借助精液常规参数、伊红染色以及精子形态等指标,筛选出18例单一因素少精子症患者(浓度<15×106/ml,其余指标均正常)和20例单一因素弱精子症患者(前向运动精子百分率<32%,其余指标均正常)用于DNA甲基化检测;提取精子样本全基因组DNA,进行亚硫酸氢盐处理、PCR扩增目的基因片段并测序;通过BIQ Analyzer软件对测序结果进行质控和DNA甲基化程度分析。20例正常生育男性精液标本作为对照组。结果:与对照组甲基化丢失率[(0.30±0.06)%]相比,少精子症患者的H19印记控制区域的DNA甲基化丢失程度显著增高[(9.19±2.45)%],尤其当精子浓度<3×106/ml时,差异达到极显著水平(P<0.01)。在弱精子症患者中H19印记控制区域的DNA甲基化丢失程度[(0.30±0.07)%]和模式均与对照组无显著差异(P=0.62)。进一步重点分析了CTCF6位点的DNA甲基化状态,少精子症患者的DNA甲基化丢失程度[(2.67±0.75)%]显著高于对照组[(0.05±0.03)%]和弱精子症组[(0.03±0.02)%],而后两者之间无显著差异(P=0.35)。结论:H19印记控制区域的DNA甲基化程度的降低与少精子症密切相关,且降低程度与精子浓度呈显著负相关,而与精子活力无关。     

五项生化指标联合检测在早期糖尿病肾病中的诊断价值分析

目的探讨血清胱抑素C(cystatin C,Cys-C)、同型半胱氨酸(homocysteine,Hcy)、超敏C-反应蛋白(hypersensitive C-reactive protein,hs-CRP)、尿β2微球蛋白(urineβ2microglobulin,U-β2MG)及尿微量白蛋白(urinary albumin,UAlb)联合检测在早期糖尿病肾病(diabetic nephropathy,DN)中的诊断价值。方法选取2012年1月至2016年5月新沂市中医医院收治的48例早期DN患者为观察组,按1:1比例抽取同期住院的48例糖尿病(diabetes mellitus,DM)不合并DN患者为对照组,对照组48例患者肾小球滤过率正常,彩超检查肾脏形态、大小正常。两组患者均于入院后24 h内分别抽取空腹肘静脉血3 ml,离心后检测血清Cys-C、Hcy、hs-CRP、U-β2MG及UAlb,Cys-C及U-β2MG检测均采用免疫透射比浊法,Hcy检测采用酶法,hs-CRP及UAlb检测均采用免疫散射比浊法,均按说明书进行操作。结果 2组入院后血清Cys-C[(1.16±0.24)mg/L vs(0.93±0.20)mg/L,t=5.161]、hs-CRP[(7.1±2.9)mg/L vs(4.4±2.7)mg/L,t=4.730]、Hcy[(22.20±3.95)mg/L vs(15.26±3.55)mg/L,t=9.047]、U-β2MG[(0.526±0.110)mg/L vs(0.407±0.136)mg/L,t=4.700]及UAlb[(42.8±6.5)mg/L vs(10.4±3.2)mg/L,t=31.022]水平对比,观察组明显高于对照组,差异均有统计学意义(P0.01)。观察组血清Cys-C、hs-CRP、Hcy、U-β2MG及UAlb检测阳性率分别为84.3%、78.6%、78.5%、89.2%及91.2%,联合检测阳性率为100%,联合检测明显提高了检测的阳性率。结论血清Cys-C、Hcy、hs-CRP、U-β2MG及UAlb是反映DM患者早期肾功能损伤敏感、准确、简便、可靠的指标,可以早期诊断DN,值得临床推广应用。     

精子DNA甲基化异常与早期自然流产的关系研究

目的:探索精子DNA甲基化水平异常与早期自然流产的关系。方法:随机选取98例符合纳入标准的配偶不明原因流产或胚停育男性为研究对象,另选取健康孕前体检男性46例作对照。行精液常规、精子形态分析,以改良精子染色质扩散法检测精子DNA碎片化指数。精子DNA甲基化水平检测采用甲基化定量试剂盒,运用比色法检测。结果:与对照组相比,早期不明原因流产组大晕环精子百分率[(45.50±26.27)%vs(36.49±23.06)%]显著降低(P=0.038),精子头部异常比例[(77.08±12.21)%vs(81.09±10.89)%]显著增高(P=0.049),精子DNA甲基化水平[(0.47±0.33)vs(0.36±0.26)ng/μl]显著降低(P=0.035);并且精子DNA甲基化水平与大晕环精子百分率呈正相关(r=0.546,P0.01)。多因素回归分析显示,精子头部异常是早期自然流产/胚停育的独立危险因素(OR=1.032,P=0.049),而精子高甲基化水平是早期自然流产/胚停育的保护因素(OR=0.244,P=0.03)。结论:精子DNA甲基化水平异常可能是不明原因早期自然流产或胚停育的原因之一。     

维生素D受体基因BsmI多态性与2型糖尿病肾病的关系

目的 研究维生素D受体(VDR)基因BsmI位点多态性与汉族人群2型糖尿病肾病(DN)的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测304例2型糖尿病患者(DM组)及100例健康体检者(NC组)VDR Bsml位点基因型和等位基因频率.根据尿白蛋白情况将DM组分为非糖尿病肾病组(DN0组,122例)、微量白蛋白尿组(DN1组,87例)、大量白蛋白尿组(DN2组,95例).83例病程5年以上仍未出现肾病的DM患者纳入L-NDN组;64例起病1年内即出现肾病的DM患者纳入EDN组.结果 DM组BB+Bb基因型和B等位基因频率均高于NC组(x2=7.088,P=0.008;x2=5.865,P=0.015).DN2组BB+Bb基因型和B等位基因频率高于NC组(x2=14.287,P=0.000; x2=12.621,P=0.000)及DN0组(x2=8.063,P=0.005;x2=8.173,P=0.004).其余组间差异均无统计学意义.EDN组BB+Bb基因型和B等位基因频率均显著高于L-NDN组(x2=7.228,P=0.007;x2=5.853,P=0.016).B等位基因阳性DN患者的尿白蛋白排泄率显著高于B等位基因阴性DN患者,差异有统计学意义(P＜0.01).BsmI位点基因型与DN发生密切相关.B等位基因阳性是DN发生及早发的危险因素(OR=2.004;0R=2.394).结论 VDRBsmI基因多态性与DN易感性相关.B等位基因阳性患者更易出现大量白蛋白尿及早期发生肾病.     

基质金属蛋白酶在糖尿病肾病作用中的研究

目的 探讨2型糖尿病及糖尿病肾病患者血清基质金属蛋白酶水平的变化及其相关影响因素.方法 选取2型糖尿病患者94例,其中2型糖尿病无蛋白尿组患者37例;微量蛋白尿组(尿白蛋白/肌酐为30 ～ 300 mg/g)27例;显著蛋白尿组患者(尿白蛋白/肌酐＞300mg/g)30例.健康体检者32名作为对照组.所有检测对象于清晨空腹抽肘静脉血,应用酶联免疫吸附法测定血清基质金属蛋白酶2及血浆纤溶酶原激活物抑制物1.结果 (1)微量蛋白尿组患者血清基质金属蛋白酶2水平为(4.3±4.1)μg/L,显著蛋白尿组患者为(4.6±4.1)μg/L,与正常对照组[2.8±0.4)μg/L]比较差异有统计学意义(P＜0.05);(2)微量蛋白尿组患者血浆纤溶酶原激活物抑制物1水平为(69±19)μg/L,显著蛋白尿组患者为(69±18)μg/L,与正常对照组[(52±30)μg/L]比较差异有统计学意义(P＜0.05);(3)相关分析结果表明,血清基质金属蛋白酶2与血浆纤溶酶原激活物抑制物1水平无相关(r =0.077,P=0.468);(4)在2型糖尿病患者中血清基质金属蛋白酶2水平与尿素氮、肌酐水平相关(r分别为0.370及0.468,P分别为0.00、0.000),血浆纤溶酶原激活物抑制物1水平与空腹血糖、甘油三酯、高密度脂蛋白、尿酸呈正相关(r分别为0.196、0.342、-0.167、0.203,P分别为0.004、0.000、0.016、0.003).结论 2型糖尿病合并蛋白尿患者血清基质金属蛋白酶2及血浆纤溶酶原激活物抑制物1水平升高,是2型糖尿病患者合并肾病的危险因素.     

肾素-血管紧张素系统基因多态性与2型糖尿病患者慢性肾脏病的相关性研究

目的探讨血管紧张素原(AGT)及血管紧张素Ⅱ1型受体(AT1R)基因多态性与2型糖尿病患者慢性肾脏病(CKD)的关系。方法将76例患CKD的2型糖尿病患者,根据肾穿刺活检病理分为糖尿病肾病(DN)组(28例)、非糖尿病性肾病(NDRD)组(30例)和DN合并NDRD组(18例);另外选择30名健康体检者作为正常对照组。采用聚合酶链反应-限制性片段长度多态性技术方法检测上述研究对象的AGT基因M235 T多态性和AT1R基因A1166C多态性。结果NDRD组的主要病理类型是为膜性肾病和IgA肾病,DN+NDRD组NDRD的主要病理类型为膜性肾病、IgA肾病和高血压性肾小动脉硬化,两组NDRD的病理类型均无显著性差异(P0.05)。DN组和DN+NDRD组AGT基因M235 T-TT基因型频率明显高于NDRD组和正常对照组(P0.05),T等位基因频率明显高于NDRD组(P0.05)和正常对照组(P0.01),NDRD组和正常对照组比较以及DN组和DN+NDRD组比较AGT-TT基因型和T等位基因频率均无明显差异(P0.05)。各组AT1R基因A1166C多态性无显著性差异。AGT基因M235 T-TT基因型为2型糖尿病肾脏疾病患者eGFR下降的危险因素。结论AGT基因M235 T-TT基因型以及T等位基因与2型糖尿病患者DN及DN合并NDRD的发生有关,与NDRD的发生无关。AGT基因M235 T-TT基因型是2型糖尿病CKD患者肾功能减退的易感因素。AT1R基因多态性与2型糖尿病患者肾脏疾病的发生发展无关。     

尿胞外体1型辅助性T细胞/2型辅助性T细胞失衡与2型糖尿病肾病的相关性

目的 探讨2型糖尿病（DM）患者尿胞外体1型辅助性T细胞/2型辅助性T细胞（Th1/Th2）的变化与2型糖尿病肾病（DN）发生发展的相关性。 方法 选取120例2型糖尿病患者及健康对照组30例为对象,根据尿白蛋白肌酐比（UACR）,2型糖尿病患者分为糖尿病非肾病组（DM,40例,UACR<30 mg/gCr）、微量白蛋白尿组（DN1,50例,UACR≥30~300 mg/gCr）和临床白蛋白尿组（DN2,30例,UACR＞300 mg/gCr）。用特异性单克隆抗体提纯尿胞外体。用酶联免疫吸附法（ELISA）检测尿胞外体干扰素γ（IFN-γ）和白细胞介素4（IL-4）水平。用多元逐步回归方法分析尿胞外体IFN-γ/IL-4比值与糖化血红蛋白（HbA1c）、胆固醇（CH）、UACR、血肌酐（Scr）、尿素氮（BUN）相关性。 结果 DM、DN1、DN2组胞外体Th1/Th2水平显著高于健康对照组（0.8089±0.2458、0.8993±0.3515、0.8571±0.2470比 0.6198±0.1769,均P < 0.01）。DN1组胞外体Th1/Th2显著高于DM组（P < 0.01）。尿胞外体IFN-γ/IL-4与UACR（r = 0.213,P = 0.015）、BUN（r=0.292,P = 0.001）呈正相关。逐步多元回归分析显示, BUN是尿胞外体IFN-γ/IL-4的独立影响因素（β = 0.246,P = 0.006）。 结论 尿胞外体Th1/Th2漂移与2型糖尿病肾病密切相关,可能在糖尿病早期肾病发病过程中起重要的作用。     

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.     

2型糖尿病合并骨质疏松患者外周血中VDR mRNA表达与25(OH)D、甘油三酯的关系研究

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)合并骨质疏松(osteoporosis,OP)患者血浆中维生素D受体(vitamin D receptor,VDR)mRNA表达水平与25羟维生素D[25 hydroxyvitamin D,25(OH)D]、甘油三酯(triglyceride,TG)的关系。方法选取2016年6月至2017年5月就诊于遵义医科大学附属医院内分泌科门诊及住院治疗的初诊2型糖尿病患者100例,据骨密度(bone mineral density,BMD)测定结果分为:单纯T2DM组48例,T2DM合并骨质疏松组(T2DM+OP组)52例;选取遵义医科大学体检中心年龄及性别相匹配的健康对照者(NC组)90例。采用电化学发光法检测血清25(OH)D水平,全自动生化分析仪检测TG,采用实时荧光定量聚合酶链反应(Real Time-PCR)检测外周血中VDR mRNA表达水平。结果T2DM+OP组与单纯T2DM组相比,血浆中25(OH)D水平降低[(8.76±3.21)～(12.46±4.35) ng/mL,t=32.423,P=0.000],VDR mRNA表达水平降低[(0.35±0.12)～(1.07±0.23),t=15.365,P=0.001],而TG水平升高[(4.1±1.26)～(2.98±0.56) mmol/L,t=11.765,P=0.000];Pearson相关分析结果显示,血浆中VDR mRNA表达与25(OH)D水平呈正相关(相关系数r=0.717,P0.05),与HbAlc、HOMA-IR、Fins、FPG、2hPG、TG呈负相关(相关系数r分别为-0.342、-0.353、-0.361、-0.546、-0.426、-0.342,P0.05)。结论外周血中VDR mRNA表达、25(OH)D水平降低及TG水平的升高可能共同参与了T2DM、骨质疏松的发生发展。     

Effects of bariatric surgery on diabetic nephropathy after 5 years of follow-up

BackgroundStudies have reported that the benefits of bariatric surgery extend beyond durable weight loss and include significant improvement in glycemic control. We hypothesized that improving diabetes control may have positive effects on end-organ complications of this disease, such as diabetic nephropathy (DN).MethodsWe identified all patients with type 2 diabetes mellitus (T2DM) who underwent bariatric surgery at our institution and had completed a 5-year follow-up. Patients’ current diabetes status (remission, improvement, or no change) was determined by biochemical analyses and medication review. The presence of DN, preoperatively and postoperatively, was determined by urinary albumin/creatinine ratio (uACR).ResultsFifty-two T2DM patients underwent bariatric surgery and had completed 5-year follow-up, including serial uACR measurements (25% male; age 51.2±10.1 years). Preoperative body mass index (BMI) was 49±8.7 kg/m², mean duration of T2DM was 8.6 years (range .3–39), and baseline HbA_1c was 7.7%±1.4%. DN, as indicated by microalbuminuria (30–300 mg/g) or macroalbuminuria (>300 mg/g), was present in 37.6% preoperatively. Of these, DN resolved in 58.3% at a mean follow-up of 66 months (range 60–92 ). Among those with no evidence of DN preoperatively, albuminuria proceeded to develop 5 years later in only 25%. The 5-year remission and improvement rates for T2DM were 44% and 33%, respectively. Mean reductions in fasting glucose and glycosylated hemoglobin (HbA_1c) were 36.6 mg/dL and 1.2%, respectively.ConclusionBariatric surgery can induce a significant and sustainable improvement in T2DM and improve or halt the development of microvascular complications such as nephropathy. Considering that diabetes is often a progressive disease, these results are clinically important and warrant further investigation.     

Polymorphisms in the Vitamin D Receptor Gene and Parathyroid Hormone Gene in the Development and Progression of Diabetes Mellitus and its Chronic Complications, Diabetic Nephropathy and Non-Diabetic Renal Disease

Background : We chose to study polymorphisms of vitamin D receptor gene (VDR) and parathyroid hormone genes (PTH), whose protein products significantly affect calcium-phosphate metabolism in kidneys and are implicated in the pathogenesis of diabetes, which may also involve kidney damage. Methods : Distribution of genotypes of four polymorphisms in VDR gene i.e TaqI (rs731236), BsmI (rs1544410) ApaI (rs7975232), FokI (rs2228570) and two polymorphisms of PTH gene, i.e. DraII (rs6256), BstBI (rs6264), were studied using PCR-RFLP. Examined groups consisted of 147 patients with diabetes (DM), 47 patients with nondiabetic renal disease (NDRD), 132 patients with diabetic nephropathy (DN) and 118 healthy subjects. Conclusion : Comparison of DN group and healthy subjects identified statistically significant difference for the FokI polymorphism in VDR gene (P<10-4) and also for the BstBI polymorphism in PTH gene (P=0,023). Differences in DraII polymorphism distribution in PTH gene were statistically significant in each group of patients compared to healthy subjects. In DN patients, the BBFFAATt combination of VDR gene was more frequent than in healthy subjects (P=0,046), and the BbFFAaTt variant was more frequent than in DM2 patients (P=0,018). The BBDD haplotype of PTH gene seems to be a predisposing factor for diabetes itself (P=0,019).     

绝经后2型糖尿病女性Wnt3a基因多态性与骨代谢的相关性

目的探讨绝经后2型糖尿病(type 2 diabetes mellitus,T2DM)女性Wnt3a基因突变与骨代谢、糖代谢、血脂代谢的相关性。方法选取新疆石河子地区绝经后T2DM女性81例,检测rs708114位点基因多态性,根据rs708114位点基因多态性分为TT组(n=19)和CC/TC组(n=62)。观察两组患者血糖代谢和其他临床特征。同时检测rs752107基因多态性,根据rs752107基因多态性分为CC组(n=44)和CT/TT组(n=37),观察两组血糖代谢和其他临床特征。结果与CC/TC组比较,TT组患者FPG显著升高[(8.84±3.65) mmol/L vs (7.10±1.68) mmol/L,P=0.005]; Hb A1c显著升高[(8.11±1.78)%vs(7.15±0.87)%,P=0.002];血清Ca显著升高[(2.34±0.20) mmol/L vs (2.24±0.15) mmol/L,P=0.032]。两组患者TG、HDL-C、LDL-C、血清P、ALP、F-BMD差异无统计学意义(P 0.05)。绝经后T2DM女性rs752107基因多态性与骨代谢、糖代谢、血脂代谢无明显相关性。结论新疆石河子地区绝经后2型糖尿病女性Wnt3a基因rs708114位点基因突变型与血糖代谢有关;可能与骨代谢有关。rs752107基因多态性与骨代谢、糖代谢、血脂代谢均无明显相关性。     

精子染色质扩散实验检测精索静脉曲张及不明原因不育患者精子DNA碎片

目的了解精索静脉曲张(VC)及不明原因不育患者精子DNA碎片的发生比例。方法改进的精子染色质扩散(SCD)实验分析精子DNA碎片。检测VC不育患者39例,不明原因不育患者57例。以生育健康成年男性32例为对照组。结果VC不育患者SCD小光晕和无光晕精子(精子DNA碎片)比值平均为(36.6±18.9)%,VC不育组明显高于对照组(12.1±5.2)%(P<0.001),而大光晕和中光晕精子比值VC不育组明显低于对照组(P<0.01);不明原因不育患者精子DNA碎片比值平均为(26.8±10.2)%,与对照组[(12.1±5.2)%]比较有显著性差异(P<0.001)。结论SCD实验表明,VC及不明原因不育患者精子DNA碎片比值增高。     

Microvascular Damage in Type 1 Diabetic Patients Is Reversed in the First Year After Simultaneous Pancreas–Kidney Transplantation

Simultaneous pancreas–kidney transplantation (SPK) is an advanced treatment option for type 1 diabetes mellitus (DM) patients with microvascular disease including nephropathy. Sidestreamdarkfield (SDF) imaging has emerged as a noninvasive tool to visualize the human microcirculation. This study assessed the effect of SPK in diabetic nephropathy (DN) patients on microvascular alterations using SDF and correlated this with markers for endothelial dysfunction. Microvascular morphology was visualized using SDF of the oral mucosa in DN (n = 26) and SPK patients (n = 38), healthy controls (n = 20), DM1 patients (n = 15, DM ≥ 40 mL/min) and DN patients with a kidney transplant (KTx, n = 15). Furthermore, 21 DN patients were studied longitudinally up to 12 months after SPK. Circulating levels of angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2) and soluble thrombomodulin (sTM) were measured using ELISA. Capillary tortuosity in the DN (1.83 ± 0.42) and DM ≥ 40 mL/min (1.55 ± 0.1) group was increased and showed reversal after SPK (1.31 ± 0.3, p < 0.001), but not after KTx (1.64 ± 0.1). sTM levels were increased in DN patients and reduced in SPK and KTx recipients (p < 0.05), while the Ang‐2/Ang‐1 ratio was normalized after SPK and not after KTx alone (from 0.16 ± 0.04 to 0.08 ± 0.02, p < 0.05). Interestingly, in the longitudinal study, reversal of capillary tortuosity and decrease in Ang‐2/Ang‐1 ratio and sTM was observed within 12 months after SPK. SPK is effective in reversing the systemic microvascular structural abnormalities in DN patients in the first year after transplantation.