胆囊结石病家系的基因多态性研究

目的 从胆囊结石病多发家系角度来探讨胆石症发病的分子基础并研究部分胆石病易感基因在胆石病家系成员中的分布及与胆石病的关系。方法 收集调查上海地区93个胆石病家系，通过胆囊B超检查证实每个家系至少有2名胆石病患，对333名家系成员（其中患239人）进行临床调查并检测血脂水平，应用PCR－RFLP（PCR－限制性多形性碎片长度）法来检测胆石病易感基因载脂蛋白B（Apo B)基因Xbal和载脂蛋白E（Apo E)基因Hha I的多态性位点基因型，分析各基因型和等位基因在家系成员中的分布情况。结果 （1）Apo B基因Xba I多态性X^ /-基因型频率在胆石组为5．9％，非胆石组为10．6％，分布无显性差异。不同的Apo B基因型，其血液生化指标无显性差异。（2）Apo E基因多态性各等位基因ε2、ε3和ε4的分布频率在胆石组分别为：6．9％、81．4％和11．7％，在非胆石组分别为：9．0％、81．4％和9．6％，分布无显性差异。年龄段为≤40岁的家系成员中，Apo E4/x(Apo E3/4,Apo E4/4)基因型在胆石组的分布频率（20．6％）显高于非胆石组（0％）（P＝0．04）。不同的Apo E基因型对血脂水平有着不同的影响，总体上看，E2／x(Apo E2/2,Apo E2/3)基因型的血清TG和HDLC显升高，LDLC显降低（P＜0．05）；而E4／x基因型的TC、LDLC、Apo B以及Apo E均显升高，HDLC、Apo A1显降低（P＜0．05）。结论 ε4等位基因可能是胆石病的易感基因，Apo B基因X^ 等位基因和胆石病的关系有待进一步确定。     

CYP450基因多态性对非创伤性股骨头坏死的影响

酒精和激素是引起非创伤性股骨头坏死的常见原因,随着非创伤性股骨头坏死发病机制研究的逐渐深入,部分研究认为酒精和激素可影响肝酶的代谢,从而对非创伤性股骨头坏死的发生、发展产生重要影响。细胞色素450酶(cytochrome P450,CYP450)作为肝酶常见的一种类型,其作用机制的研究逐渐得到医学研究者的青睐。随着CYP450研究深入,部分研究认为CYP450易感基因位点的变化可能是非创伤性股骨头坏死的发病机制,本文通过综述CYP450相关基因的多态性研究进展,对临床以及实验研究非创伤性股骨头坏死作用机制提供一定的参考和借鉴。     

单核苷酸多态性与非创伤性股骨头坏死相关性研究进展

非创伤性股骨头坏死是临床上常见的骨科难治性疾病,根据病因可分为激素性、酒精性、自发性股骨头坏死.其发病机制尚未研究清楚,目前受到广泛接受的有血管内凝血学说、脂代谢紊乱学说等.基因和环境因素都在本病的发病中起关键作用,但一般认为环境因素在一定的基因背景下才能触发发病.近年来大量研究证实了易感基因与非创伤性股骨头坏死的发病之间的关联性.单核苷酸多态性(single nucleotide polymorphism,SNP)是指基因组序列中的单核苷酸(A、T、C或G)改变时发生的DNA序列多态性.它是人类可遗传变异中最常见的一种,占所有已知多态性的90％以上.由于SNP具有高密度、稳定和易于分型检测等优点,作为第3代分子遗传标记在疾病特别是多基因疾病研究领域显示了巨大的优势.     

股骨头缺血性坏死骨质含量与VEGF、bFGF、BMP-2 mRNA表达的相关性研究

目的坏死骨的血管再生及骨修复能力与VEGF、bFGF与BMP-2多种生长因子关系密切,通过观察股骨颈骨折、创伤性及非创伤性股骨头缺血性坏死(avascular necrosis of femoral head,ANFH)的股骨头局部上述因子的表达变化,并与其组织病理学的骨质含量指标进行相关性分析,为进一步探讨ANFH的发病机制及临床针对不同病因进行个性化治疗提供实验依据。方法取59例人工全髋关节置换术患者自愿捐赠的股骨头标本进行观察。创伤性ANFH 22例(A组),Ficat分期:Ⅲ期13例,Ⅳ期9例。非创伤性ANFH 19例(B组),Ficat分期:Ⅲ期11例,Ⅳ期8例;其中激素性10例,酒精性7例,原因不明2例。新鲜股骨颈骨折18例(C组)。3组患者性别、年龄等一般资料比较,差异均无统计学意义(P>0.05)。采用双能X线骨密度仪测量股骨头负重区骨密度;大体观察组织病理学改变,HE染色光镜及扫描电镜下观察其病理变化,计算空骨陷窝百分比及骨小梁面积百分比,并采用原位杂交技术分别对其VEGF、bFGF、BMP-2 mRNA表达进行检测。结果 A、B组骨密度均低于C组,B组低于A组,组间差异均有统计学意义(P<0.05)。A、B组股骨头形态不规则,光镜下见坏死区骨小梁稀疏、不完整,有大量空骨陷窝;健存区A组有较多纤维组织增生,B组髓腔内脂肪细胞增生、肥大。扫描电镜示A、B组大多骨细胞脂肪变性、坏死,骨基质内见脂肪细胞增生。C组均呈正常股骨头结构。A、B组空骨陷窝百分比均高于C组,骨小梁面积百分比均低于C组,差异均有统计学意义(P<0.05);A、B组间仅空骨陷窝百分比差异有统计学意义(P<0.05)。A组与B组VEGF、BMP-2、bFGF mRNA阳性染色面积百分比及吸光度(A)值均明显低于C组(P<0.05);A组BMP-2、bFGF mRNA两指标均较B组高(P<0.05),但VEGF mRNA A、B组间差异无统计学意义(P>0.05)。上述各因子表达强度与骨密度、骨小梁面积百分比成正相关,而与空骨陷窝百分比成负相关。结论创伤性ANFH的股骨头修复能力强于非创伤性ANFH,创伤性与非创伤性ANFH股骨头局部VEGF、bFGF、BMP-2 mRNA表达均降低。     

胆囊结石病家系的基因多态性研究

目的 从胆囊结石病多发家系角度来探讨胆石症发病的分子基础并研究部分胆石病易感基因在胆石病家系成员中的分布及与胆石病的关系。方法 收集调查上海地区93个胆石病家系,通过胆囊B超检查证实每个家系至少有2名胆石病患者,对333名家系成员（其中患者239人）进行临床调查并检测血脂水平,应用 PCR-RFLP（PCR-限制性多形性碎片长度）法来检测胆石病易感基因载脂蛋白 B（Apo B）基因Xbal和载脂蛋白E（Apo E）基因Hha I的多态性位点基因型,分析各基因型和等位基因在家系成员中的分布情况。结果 （1）Apo B基因 Xba　I多态性 X+/-基因型频率在胆石组为5.9％,非胆石组为10.6％,分布无显著性差异。不同的Apo　B基因型,其血液生化指标无显著性差异。（2）Apo E基因多态性各等位基因ε2、ε3和ε4的分布频率在胆石组分别为:6.9％、81.4％和11.7％,在非胆石组分别为:9.0％、81.4％和9.6％,分布无显著性差异。年龄段为≤40岁的家系成员中,Apo E4/x（Apo E3/4,Apo E4/4）基因型在胆石组的分布频率（20.6％）显著高于非胆石组（0％）（P=0.04）。不同的Apo E基因型对血脂水平有着不同的影响,总体上看,E2/x（Apo E2/2,Apo E2/3）基因型者的血清TG和HDLC显著升高,LDLC显著降低（P<0.05）;而E4/x基因型者的TC、LDLC、Apo     

褪黑素受体1A基因多态性与青少年特发性脊柱侧凸相关性研究

目的研究褪黑素受体1A基因（MTNR1A）多态性与青少年特发性脊柱侧凸（AIS）发生发展的关系。方法共纳入226例AIS患者及277例正常对照者。记录AIS患者组最大Cobb角。采用PCR-RFLP的方法对MTNR1A基因启动子区域多态性位点rs2119882进行基因分型。结果AIS患者组MTNR1A基因多态性位点rs2119882的基因型及等位基因分布与正常对照组比较没有明显差异。在AIS组内,多态性位点rs2119882不同基因型所对应的最大Cobb角没有明显差异。结论MTNR1A基因rs2119882位点多态性与AIS的发生发展都没有关系。     

股骨头缺血坏死的血液流变学临床研究

目的　探讨创伤性与非创伤性股骨头缺血坏死 (ANFN)患者的血液流变学特性。方法　选取创伤性与非创伤性股骨头缺血坏死患者以及其它骨创伤患者共 3组 ,每组 2 8例 ,进行血液流变学指标检测分析。结果　创伤组和对照组比较 ,血小板、血脂含量、血液流变学指标均无明显差异 (P >0 0 5 )。非创伤组和对照组比较 ,全血低切粘度、血浆纤维蛋白原、甘油三脂明显增高 (P <0 0 1)。结论　血液高粘滞状态与创伤性ANFH无明显关系 ,但是可能参与非创伤性ANFH的发病。它的形成可能与高脂血症有关 ,同时还有其它未知病理因素参与。在临床上对有ANFH危险因素的患者进行血液流变学监测 ,可能起到预警作用     

结直肠癌患者IL-6基因启动子-174G→C多态性研究

目的：观察结直肠癌患者是否存在IL-6基因启动子-174G→C位点的多态性。方法：采用PCR扩增、限制性内切酶片段长度多态性（RFLP）分析判断46例结直肠患者IL-6启动子-174G→C多态性。结果：全组结直肠癌患者IL-6基因启动子-174位点均为GG型。结论：本组结直肠癌患者中未发现IL-6基因启动子-174位点的多态性。     

非创伤性股骨头坏死与血浆脂蛋白的相关性研究

目的　研究非创伤性股骨头坏死与血浆脂质变化的相关性。方法　研究对象 12 0例 ,其中 60例非创伤性股骨头坏死患者和 60例正常人 ,采用奥林帕斯 (Olypas)AU 40 0全自动生化分析仪 ,检测总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白 (HDL)、低密度脂蛋白 (LDL)、载脂蛋白AI(ApoAI)、载脂蛋白B(ApoB)等指标。结果　股骨头坏死组与正常对照组血浆脂质及载脂蛋水平比较 ,TC、TG、LDL、ApoB明显升高 (P <0 0 5 ) ,HDL、ApoAI明显降低 (P <0 0 5 ) ,ApoB/ApoAI比值显著升高 (P <0 0 0 1)。结论　非创伤性股骨头坏死的发生和发展与血浆中的脂蛋白有密切关系 ,ApoB/ApoAI比值升高对估计非创伤性骨坏死的发生具有一定的临床意义     

青少年特发性脊柱侧凸女性患者瘦素基因启动子区-2548G/A基因多态性研究

目的:探讨瘦素基因启动子区-2548G/A(rs7799039)基因多态性与女性青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)发生发展、异常生长模式及侧凸类型之间的相关性。方法:收集451例AIS女性患者及335例正常同龄女性青少年的静脉血标本,采用PCR-RFLP方法对两组的瘦素基因启动子区-2548G/A(rs7799039)多态性位点进行基因分型,比较两组间基因分型的差异,分析AIS组中基因分型与患者Cobb角和人体测量学指标的关系。结果:AIS组rs7799039位点基因型和等位基因频率与正常对照组之间无明显差异;在AIS组内,rs7799039位点不同基因型所对应的初诊Cobb角、校正身高、BMI、月经初潮年龄及Risser征均没有显著性差异;rs7799039位点等位基因多态性分布情况在不同侧凸类型AIS患者和对照组之间无统计学差异。结论:瘦素基因启动子区-2548G/A(rs7799039)基因多态性与女性AIS的发生发展、异常生长模式及不同侧凸类型之间都没有明显的相关性。     

Rb基因多态性食管癌遗传易感性的研究

目的 探讨Ｒｂ基因２０内含子ＶＮＴＲ、１７内含子ＲＦＬＰ的多态性与食管癌遗传易感性的关系。方法 应用ＰＣＲ技术对陕西正常人群（５６例）、食管癌组织（４７例）及癌旁组织（３１例）Ｒｂ基因２０内含子ＶＮＴＲ位点、１７内含子ＲＦＬＰ进行检测。结果在正常人群中Ｒｂ基因２０内含了共检测出１０个等位基因片段,等位基因片段范围在３２０ｂｐ～２６０ｂｐ之间,杂合率为７０．０％,ＰＩＣ为８６．０％。在癌组织中杂合率     

Apo A1/Apo B ratio and acute coronary syndrome among peritoneal dialysis patients

BackgroundAcute coronary syndrome (ACS) is prevalent in continuous ambulatory peritoneal dialysis (CAPD) patients. However, the association between the apoprotein profile and ACS is not well known. Therefore, we aimed to investigate the relationship between apoproteins and ACS in CAPD patients.MethodsEighty-one CAPD patients were included in this retrospective study. The primary endpoint was ACS. Predictors were baseline apoprotein levels, particularly the ratio of apoprotein A1 (Apo A1)/apoprotein B (Apo B). Cox regression was used to determine the relationship between Apo A1/Apo B and ACS.ResultsDuring follow-up, 34 (41.98%) CAPD patients experienced an ACS. ACS patients had higher levels of total cholesterol (p = 0.03), low-density lipoprotein cholesterol (LDL-C) (p = 0.04), C-reactive protein (p = 0.01), and Apo B (p < 0.01). However, hemoglobin (p = 0.01) and Apo A1/Apo B (p < 0.01) were lower in the ACS group than the non-ACS group. Patients with Apo A1/Apo B ≥ 1.105 experienced fewer ACS compared with those with Apo A1/Apo B < 1.105 (33.33% vs. 75.56%, p = 0.03). In Cox regression, Apo A1/Apo B (RR, 0.06; 95% CI, 0.00-0.77; p = 0.03) was independently associated with ACS.ConclusionsApo A1/Apo B was strongly associated with ACS and may be considered as a predictor of future ACS in CAPD patients.     

上海闵行地区胆固醇结石病易患因素分析

目的 研究上海郊县闵行地区胆固醇结石病人载脂蛋白（Ａｐｏ）Ｂ基因ＸｂａⅠ多态性,以及血脂、胆囊收缩功能的改变,探讨胆石病危险因素。方法 对３４例胆囊结石２和１０１例正常要,采用ＰＣＲ－ＲＦＬＰ方法测定ＡｐｏＢ基因ＸｂａＩ多态性、检测血脂和胆囊壁厚、胆囊空腹容积、残余容积、排空率的改变。结果 胆石组ＡｐｏＢ基因Ｘ＋／－基因型（２３．５３％）和Ｘ＋等基因（１１．７６％）同于对照组（７．９２％,３．９６     

Relationships between tumour necrosis factor-α, interleukin-12B and interleukin-10 gene polymorphisms and hepatitis B in Chinese Han haemodialysis patients

Aim: To investigate the possible association of gene polymorphisms of tumour necrosis factor (TNF)‐α (‐238 and ‐308), interleukin (IL)‐10 (‐592 and ‐819) and 3′ untranslated region (3′UTR) of the IL12B (‐1188) and hepatitis B in Chinese Han haemodialysis (HD) patients. Methods: The genotyping of TNF‐α ‐238 and ‐308, IL‐10 ‐592 and ‐819 and 3′UTR of the IL12B were performed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. Results: The TNF‐α‐238 A allele, the IL12B 3′UTR C/C, C/A genotypes were associated with decreased susceptibility to hepatitis B viral infection (P = 0.047, P= 0.003 and P = 0.001 respectively). The frequencies of IL‐10–592 A/A genotype, IL‐10–819 T/T genotype were lower in the HBV persistence group (P = 0.029 and P = 0.019) than those in the virus clearance group. Conclusions: TNF‐α and IL12B 3′UTR gene polymorphisms may be associated with HBV susceptibility and IL‐10 gene polymorphisms may be related to the HBV persistence infection in Chinese Han HD patients.     

The role of collagen type I α2 polymorphisms: intracranial aneurysms in Koreans

BackgroundThe COL1A2 is located on chromosome 7q22.1, and mutations in this gene have been associated with the development of IAs. In this study, we investigated whether the rs42524 and rs2621215 polymorphisms of the COL1A2 gene are associated with the development of cerebral aneurysms in the Korean population.MethodsThis was a hospital-based case control study conducted at Chonnam University Hospital, Gwangju, Korea. The study population consisted of 320 patients who had been treated for IA and 189 healthy hospital-based controls (angiographically negative for an IA). Two polymorphic loci were amplified by polymerase chain reaction, namely, rs42524 in exon 28 and rs2621215 in intron 46 of the COL1A2 gene, and analyzed by RFLP using HhaI or BfaI restriction enzymes, respectively.ResultsThe genotype frequencies of rs42524 in cases were 88.0%, 11.4%, and 0.6% for the GG, GC, and CC genotypes, respectively, and in controls were 88.9%, 10.0%, and 1.1%, respectively. Similarly, the genotype frequencies of rs2621515 in cases were 88.0%, 10.1%, and 0.2% for the TT, TG, and GG genotypes, respectively, and among controls were 92.1%, 7.9%, and 0%, respectively.ConclusionThe rs2621215 SNP in intron 46 of the COL1A2 gene was found to be marginally associated with an increased risk of IA development in the Korean population examined. In contrast, rs42524 showed no association with an increased risk of IA development.     

Perinatal Origin of Adult Disease

Background—Because of current limitations in improving metabolic support to the brain during hypothermic circulatory arrest (HCA), attenuation of ischemia‐reperfusion injury remains an area of therapeutic intervention of relevance. Apotransferrin (Apo‐Tf), alpha 1‐acid glycoprotein (AGP), and C1‐esterase inhibitor (C1‐INH) have been herein evaluated as potential beneficial agents in reducing the ischemia‐reperfusion injury in a surviving model of HCA.

Methods—Apo‐Tf 100?mg/kg (n?=?6), C1‐INH 50 IU/kg (n?=?6), AGP 100?mg/kg (n?=?6), or NaCl 0.9% 2?ml/kg (n?=?6) were randomly administered to 24 juvenile pigs after a 75‐min period HCA at a brain temperature of 18°C.

Results—Animals in the Apo‐Tf group had a slightly better 7‐day survival (66.7%) compared with the other study groups (50%), but such a difference was not statistically significant. Some favorable changes in the brain glucose metabolism parameters were observed in the AGP, C1‐INH, and Apo‐Tf groups, but these did not reach statistical significance. Semiquantitative analysis of the histopathological findings did not show any significant difference between the study groups. However, only two out of four surviving animals in the Apo‐Tf group developed brain infarction, whereas all three survivors of the remaining study groups developed brain infarction.

Conclusions—Although the small size of the study groups may affect the present findings, none of the metabolic and hemodynamic parameters as well as outcome endpoints indicate a substantial therapeutic efficacy of Apo‐Tf, AGP, and C1‐INH as neuroprotective agents after experimental HCA.     

声辐射力脉冲弹性成像及超微血流成像技术评估IgA肾病严重程度

目的 分析声辐射力脉冲（ARFI）弹性成像及超微血流成像（SMI）评估IgA肾病（IgAN）严重程度的价值。方法 将124例经穿刺右肾中下极活检病理证实的IgAN患者根据估测肾小球滤过率（eGFR）分为A、B、C组。A组32例,eGFR>90 ml/（min·1.73 m²）;B组54例,eGFR 60~90 ml/（min·1.73 m²）;C组38例,eGFR<60 ml/（min·1.73 m²）,于肾活检前3天内行ARFI及SMI。将取样框置于右肾中下极、两肾柱间邻近肾被膜皮质区域,分别检测剪切波速度（SWV）及血流阻力指数（RI）。对比3组SWV、RI,以Pearson相关分析法观察SWV与RI的相关性。结果 A、B、C组SWV逐渐降低,RI逐渐增加,组间两两比较差异均有统计学意义（P均<0.05）。相关性分析结果显示,A、B、C组SWV均与RI呈负相关（r=-0.709、P<0.001,r=-0.792、P<0.001,r=-0.473、P=0.003）。结论 利用ARFI及SMI能无创评估IgAN严重程度。     

Single nucleotide polymorphisms near IL28B gene and response to treatment of chronic hepatitis C in hemodialysis patients

Abstract

Background: It has been shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene were associated with sustained virological response following standard antivirological treatment of chronic hepatitis C. Objectives: The aim of the study was to evaluate the association between SNPs near the IL28B gene and response to the treatment of chronic hepatitis C in hemodialysis patients. Patients and methods: The study group included 24 hemodialysis patients with chronic hepatitis C routinely treated with pegylated interferon α-2?a. HCV genotype 1 was the cause of chronic hepatitis C in all study participants. Sustained virological response was determined by an assay with a sensitivity of 20?IU/mL, 6 months after completion of the antivirological treatment. The genotyping of the three most widely studied IL28B gene polymorphisms (rs12979860, rs8099917, and rs12980275) was performed in all study participants. Results: Sustained virological response was achieved in 50% of the treated patients. The treatment response was significantly associated with the CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 (p?=?0.003, p?=?0.009, and p?=?0.012, respectively). Conclusions: The three most widely studied SNPs near the IL28B gene were associated with sustained virological response following antivirological treatment of chronic hepatitis C in hemodialysis patients.     

Caspase-9(-1263A/G)多态性与中国汉族男性士兵下腰痛的相关性研究

目的 探索凋亡相关基因Caspase-9(-1263A/G)多态性与中国汉族男性士兵的训练性下腰痛及疼痛程度的相关性。方法 于某步兵团和某装甲团分别选取247名和245名中国男性汉族士兵,按诊断标准分为下腰痛组和对照组,对下腰痛组患者进行疼痛视觉模拟量表(visual analogue scale,VAS)评分。抽取全部研究对象的外周静脉血,提取白细胞DNA,聚合酶链式反应(polymerase chain reaction, PCR)扩增,DNA测序仪检测Caspase-9(-1263A/G)位点的基因型,分析该位点与训练性下腰痛是否存在相关性。结果 在步兵群体中,下腰痛组AA基因型的分布频率明显低于对照组,而GG基因型的分布频率要高于对照组,组间差异均具有统计学意义(P< 0.01);在装甲兵群体中,AA基因型在下腰痛组中的分布频率同样低于对照组,GG基因型高于对照组,组间差异均具有统计学意义(P< 0.01)。Caspase-9(-1263A/G)位点与下腰痛士兵VAS评分的相关性分析表明,携带GG基因型的装甲兵患者的VAS评分更高,差异具有统计学意义(P< 0.05),下腰痛更为严重,但在步兵群体中不存在这种相关性,差异无统计学意义(P >0.05)。结论 Caspase-9(-1263A/G)多态性与中国汉族步兵和装甲兵的训练性下腰痛相关,并且与装甲兵下腰痛患者的严重程度存在相关性。     

急性Stanford A型主动脉夹层术后急性肾损伤的肾叶间动脉血流动力学改变

目的探讨急性Stanford A型主动脉夹层术后急性肾损伤(AKI)的超声血流动力学指标改变情况。方法收集40例接受手术治疗的急性Stanford A型主动脉夹层患者,分别在手术前1天、术后即刻(进入重症监护室)、手术后6、24、48h测量双肾叶间动脉收缩期峰值流速(PSV)、舒张期最小流速(EDV)、搏动指数(PI)、阻力指数(RI),同时记录血肌酐(sCr)水平和尿量。以AKIN为标准将患者分为AKI组和无AKI组,比较两组间差异。结果 40例患者中,AKI组27例,无AKI组13例。无AKI组与AKI组患者术后6、24h肾叶间动脉EDV、PI、RI差异有统计学意义(P均0.05)。肾叶间动脉EDV与sCr呈负相关(r=-0.508,P=0.001),PI、RI与SCr呈正相关(r=0.411、0.443,P=0.009、0.005)。结论通过肾叶间动脉EDV、PI、RI可早期预测AKI发生,术后6、24h是超声测量肾叶间动脉血流动力学指标预测肾损伤的最佳时间。