哮喘患者IL-13基因Intron3+1923位点C/T、β2-AR基因R16G单核苷酸多态性及HLA等位基因频率表达对外周血T淋巴细胞亚群和IgE的影响

目的探究白细胞介素-13(interleukin-13,IL-13)基因、β2肾上腺素能受体(β2 adrenergic receptor,β2-AR)基因、人类白细胞抗原(human leukocyte antigen,HLA)基因对哮喘患者外周血T淋巴细胞亚群和血清IgE的影响。方法收集2019年1月至2020年1月就诊的90例哮喘患者作为疾病组,另收集同期体检的90例健康志愿者作为健康人对照组,使用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)检测2组IL-13基因Intron3+1923位点C/T多态性、β2-AR基因R16G单核苷酸多态性及HLA等位基因频率;采用流式细胞术测定2组T淋巴细胞亚群的表达水平,ELISA法检测血清IgE的表达水平。结果疾病组和健康人对照组IL-13基因Intron3+1923位点中TT(15.56%vs 0%,χ²=16.873,P=0.000)、TC(43.33%vs 27.78%,χ²=5.276,P=0.022)、CC(41.11%vs 72.22%,χ²=19.707,P=0.000)基因型频率的差异有统计学意义;此外,与健康人对照组比较,疾病组β2-AR基因R16G多态性中AA型频率(47.78%vs 21.11%,χ²=15.750,P=0.000),HLA 0401型(13.33%vs 0%,χ²=14.282,P=0.000)、0601型(12.22%vs 0%,χ²=13.015,P=0.000)频率均明显升高。IL-13基因Intron3+1923位点TT及TC型CD3⁺、CD4⁺、CD4⁺/CD8+表达水平较CC型明显降低(P均<0.01),而IgE表达水平(P均<0.01)明显升高。β2-AR基因R16G位点AA型CD3⁺、CD4⁺、CD4⁺/CD8+表达水平较GG、AG型明显降低(P均<0.01),而IgE表达水平明显升高(P均<0.01)。HLA基因0401及0601型较0101/0102、0103、0501型明显降低(P均<0.01),而IgE水平明显升高(P均<0.01)。结论IL-13基因Intron3+1923位点C/T、β2-AR基因R16G位点AA、HLA基因0401及0601型突变等位基因频率在哮喘患者中的表达水平存在显著差异,可能是哮喘发病的危险因素。     

白细胞介素-13基因多态性与哮喘易感的关系

目的:探讨白细胞介素(IL)-13外显子4单核苷酸多态性A2 044G基因与本地区人群哮喘易感性的相关性。方法:采用聚合酶链反应技术(PCR)对36例有明显支气管哮喘家族史的患者和20名健康对照者的IL-13 exon 4基因多态性进行检测,并进行序列测定。结果:正常对照组IL-13 exon 4第2044等位基因为A的频率是18%,为G是82%,支气管哮喘家族史的患者IL-13 exon 4第2044等位基因为A的频率是24%,为G是76%,与测序结果相同,经统计学分析,支气管哮喘组和正常对照组的等位基因频率差异具有统计学意义P<0.05。对照组GG、GA、AA基因型频率分别为66.1%、31.7%和2.1%;哮喘组GG、GA、AA基因型频率分别为60.0%、32.0%和8.0%。结论:IL-13 2044位A/G多态性与支气管哮喘的发病密切相关。     

IL-13-1112C＞T和CYP3A4*1G基因多态性与青霉素过敏反应的遗传相关性分析

目的探讨白介素-13(IL-13)启动子区-1112CT及CYP3A4*1G位点基因多态性与青霉素过敏易感性的相关性。方法以甘肃地区汉族人群临床青霉素过敏反应的211例患者和220例对照为研究对象,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测IL-13-1112CT和CYP3A4*1G等位基因及基因型频率的遗传分布,Hardy-Weinberg检验确认标本的群体代表性,用χ2检验进行关联分析。结果 IL-13-1112CT位点的CC、CT、TT基因型及C、T等位基因在过敏组和对照组间差异有统计学意义(χ2分别为9.280,10.257,P均0.05);过敏组CT+TT基因型频率为50.2%,高于对照组的35.0%(χ2=10.235,P0.05);过敏组T等位基因频率为28.9%,高于对照组的20.0%(χ2=9.280,P0.05);且按性别分组后,男性过敏组和对照组间差异仍有统计学意义(χ2=9.215、9.525,P均0.05)。CYP3A4*1G位点的基因型和等位基因频率在过敏组和对照组间差异均无统计学意义(χ2分别为1.169、0.360,P均0.05)。且按性别分组后差异仍无统计学意义。结论 IL-13-1112CT可能是青霉素药物过敏反应的易感基因,并且与男性患者的关联性更强;CYP3A4*1G基因多态性与青霉素过敏无关。     

IL-17基因多态性与支气管哮喘患儿血清TIgE、ECP的关系分析

目的分析白细胞介素(IL)-17基因多态性与支气管哮喘患儿血清总IgE(TIgE)、嗜酸性粒细胞阳离子蛋白(ECP)的关系。方法将该院2018年1—12月收治的60例哮喘患儿设为哮喘组,同期于该院行健康体检的60例健康儿童设为对照组,采用PCR-限制性片段长度多态性分析法检测2组IL-17基因多态性,采用免疫比浊法、酶联免疫吸附试验法分别检测其血清TIgE、ECP水平,比较2组IL-17基因多态性、TIgE和ECP水平及不同基因型、不同等位基因型患儿血清TIgE、ECP水平。结果哮喘组中IL-17A-152G/A位点中AA型基因频数频率、A等位基因频数频率,IL-17F 7488T/C位点中TT型基因频数频率、T等位基因频数频率,血清TIgE、ECP水平均显著高于对照组(P<0.05)。哮喘组IL-17A-152G/A位点AA型基因血清TIgE显著高于AG、GG型(P<0.05)。IL-17A-152G/A位点A等位基因携带患儿血清TIgE显著高于非A等位基因携带患儿(P<0.05)。哮喘组IL-17F 7488T/C位点不同基因型、等位基因携带者间血清TIgE、ECP与对照组比较,差异无统计学意义(P>0.05)。结论IL-17A-152G/A基因多态性与哮喘易感性有关,变异等位基因A携带患儿哮喘风险更高,尤其是突变纯合子AA基因型,野生型TT纯合子与哮喘也有一定关联性;且IL-17基因多态性虽与血清ECP均无明显关联,但血清ECP在哮喘患儿中仍明显高表达。     

我国广东地区汉族人群类风湿性关节炎患者 IL-6启动子基因多态性的研究

目的了解我国广东地区汉族人群白细胞介素-6（IL-6）基因启动子-572C/G和-174G/C位点单核苷酸多态性对类风湿性关节炎（RA）的影响。方法应用序列特异性引物-聚合酶链反应（PCR-SSP）检测168名体检健康者和120例RA患者的IL-6基因启动子-572和-174位点的基因型。结果我国广东地区汉族人群IL-6基因启动子-572位点存在C→G的突变,其基因型和等位基因频率分布在RA组和对照组比较差异有统计学意义（基因型频率：2χ=16.14,P=0.003;等位基因频率：2χ=16.71,P〈0.001）,其G等位基因在RA患者中明显低于健康对照组[比值比（OR）=0.36,95%可信区间（CI）：0.21-0.61];-174位点存在G→C的突变,其基因型和等位基因分布频率在两组间差异亦有统计学意义（基因型频率：2χ=25.75,P〈0.01;等位基因频率：2χ=25.99,P〈0.01）,其C等位基因在RA组明显高于健康对照组（OR=2.26,95%CI：1.91-2.68）。结论我国广东地区汉族人群IL-6基因启动子存在-572C/G与-174G/C的单核苷酸多态性,且这2个位点多态性与RA有关,其中IL-6-572位点的G等位基因可能对RA有保护作用,而IL-6-174位点等位基因C可能与RA发病的易感性有关。     

宁夏地区Graves′病与CTLA-4基因多态性相关性研究

目的探讨细胞毒性T淋巴细胞相关抗原4(CLTA-4)基因多态性与宁夏人群Graves′病(GD)的相关性。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析61例GD患者和60名对照者的CTLA-4基因第一外显子(49)A/G位点和启动子(318)C/T位点多态性。结果GD患者组与对照组之间CTLA-4基因SNP(49)A/G的基因型分布(χ2=9.277,P<0.05)及等位基因频率(χ2=10.831,P<0.05)差异有统计学意义;SNP(318)C/T的基因型分布(χ2=0.446,P>0.05)及等位基因频率(χ2=0.489,P>0.05)差异无统计学意义。结论CTLA-4基因第一外显子的(49)A/G位点的多态性与宁夏地区GD的发生可能相关。     

白细胞介素-18基因多态性与肺结核病易感性的关系

目的：通过病例-对照研究,探讨白细胞介素-18（IL-18）基因启动子区-607C/A、-137G/C位点单核苷酸多态性（SNP）与肺结核病的关系。方法：采用序列特异性引物PCR（PCR-SSP）及测序技术检测深圳地区汉族人群肺结核患者200例及健康对照者197例IL-18启动子区-607 C/A 、-137G/C位点多态性基因型。采用直接计数法计算各组基因型频率及等位基因频率,进行χ2 检验。以P值＜0.05为具有统计学意义。结果：肺结核患者IL-18启动子区-607位点A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为19.5%、55.0%、25.5% ;A、C等位基因频率分别为47.0%、53.0%。健康对照者A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为22.8%、46.7%、30.5%;A、C等位基因频率分别为46.2%、53.8%。两组人群-607位点基因型及等位基因分布无明显差异(P>0.05)。肺结核患者IL-18启动子区-137G/C位点C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为4.5%、18.5%、77.0%;C、G等位基因频率分别为13.8%、86.2%。健康对照者C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为5.6%、25.9%、68.5%;C、G等位基因频率分别为18.5%、81.5%。两组人群-137位点基因型分布无明显差异(P>0.05)。结论：IL-18启动子区-607、-137位点基因多态性与中国汉族人群肺结核病易感性无关。     

蛋白酶体α6亚单位基因1233A/T位点多态性与脑梗死的关系

目的探讨中国汉族人群中蛋白酶体α6亚单位(PSMA6)基因1233A/T(-1520C/T)位点的多态性与脑梗死的相关性。方法 2012年1月至2015年4月,选择脑梗死患者211例(病例组)和健康体检者201例(对照组),应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)检测PSMA6基因1233A/T位点单核苷酸多态性,并分析其基因型及等位基因频率在脑梗死患者和正常人群中的分布特点。结果两组CC、CT+TT基因型频率及C、T等位基因频率均无显著性差异(χ20.053, P 0.05)。性别分层后,无论男性、女性,两组CC、CT、TT基因型频率和C等位基因频率均无显著性差异(χ22.735, P 0.05)。结论 PSMA6基因1233A/T位点可能与脑梗死的发病无关。     

白细胞介素13基因多态性与支气管哮喘的关系

支气管哮喘(简称哮喘)是由多种免疫细胞及炎症因子参与的慢性气道炎症性疾病,近几年其患病率和复发率有逐年增高的趋势,严重影响患者的身心健康。白细胞介素13(IL-13)作为最重要的细胞因子之一,在哮喘的发病中起重要作用。现已发现十余个与哮喘密切相关的IL-13基因位点,这些基因位点的单核苷酸多态性与IL-13的表达、血清总Ig E水平及气道高反应性等密切相关。本文就IL-13基因+1923C→T、+2044G→A(rs20541)及-1112 C→T(rs1800925)多态性与哮喘关系的相关研究予以综述。     

慢性乙型肝炎患者IL-1RN(T+8006C)位点基因多态性分析

目的探讨白细胞介素-1受体拮抗剂基因(IL-1RN)第2号外显子+8006T/C位点基因多态性在慢性乙型肝炎患者中的分布及其相关性。方法采用聚合酶链反应-限制性片段长度多态性的分析方法,对450例慢性乙型肝炎患者和420例对照者IL-1RN(T+8006C)位点基因多态性进行检测,计算并分析其等位基因和基因型频率。结果观察组和对照组IL-1RN(T+8006C)位点基因型的分布最常见为TT型,TC型次之,CC型则较为罕见;在不同年龄组、不同性别间其分布比较,差异无统计学意义(P0.05);观察组C型等位基因及TC基因型频率明显低于正常对照组,差异有统计学意义(P0.01)。结论 IL-1RN(T+8006C)位点等位基因及基因型的分布不存在年龄和性别间的区别,但与慢性乙型肝炎存在相关性,在乙型肝炎病毒感染中,C型等位基因可能具有保护作用。     

Involvement of a Ca 2+ Channel Gene in Familial Hemiplegic Migraine and Migraine With and Without Aura

A gene for familial hemiplegic migraine, a subtype of migraine with aura, was assigned to chromosome 19p13. In this region, we identified a brain-specific P/Q-type calcium channel α1a-subunit gene, CACNA1A, with 47 exons covering 300 kb. Sequencing of all exons and their flanking surroundings revealed polymorphic variations, including a (CA)0-repeat anti a (CAG)n-repeat in the 34 untranslated region. In patients with familial hemiplegic migraine, we found four different missense mutations in conserved functional domains. One of the mutations has occurred on two different haplotypes in unrelated familial hemiplegic migraine families. Moreover, in episodic ataxia type 2, we found two mutations disrupting the reading frame. Thus, familial hemiplegic migraine and episodic ataxia type 2 can be considered as allelic channelopathies. Involvement of this familial hemiplegic migraine locus in migraine with and without aura was demonstrated by sib-pair analysis. We showed an increase of shared marker alleles of locus D19S394 , which is tightly linked to the gene. The association between the α1A calcium channel and familial hemiplegic migraine, and the increase of shared alleles in migraine-affected sib-pairs, have uncovered a new pathway for the pathophysiology of migraine. This finding may provide a rationale for the development of specific prophylactic therapy for migraine and other (paroxysmal) cerebral disorders.     

11~13+6周规范化超声检查的临床应用

目的 评估11~13⁺⁶周规范化超声检查筛查胎儿严重畸形的效能。方法 分析接受11~13⁺⁶周超声检查且有随访结果的3 515胎胎儿早孕期超声表现,并评估11~13⁺⁶周规范化超声检查诊断胎儿畸形的价值。结果 11~13⁺⁶周规范化超声检查诊断胎儿畸形的敏感度为80.00%（60/75）、特异度为99.42%（3 420/3 440）、准确率为99.00%（3 480/3 515）,阳性预测值为75.00%（60/80）、阴性预测值为99.56%（3 420/3 435）。严重结构畸形分布5大系统,共21种畸形。结论 11~13⁺⁶周规范化超声检查可筛查胎儿异常包括胎儿严重结构畸形及染色体畸形。     

A single isoform of the Na+/K+-ATPase α-subunit in Diptera: evidence from characterization of the first extracellular domain

The first extracellular domain of the α-subunit of the Na⁺/K⁺-ATPase (sodium/potassium pump) is functionally important, affecting sensitivity of the enzyme to cardiac glycosides (e.g. ouabain) and being implicated in the transport of K⁺. This domain is also variable among mammalian isoforms of the α-subunit. Using PCR, we have isolated from seven insect species with contrasting physiologies a DNA fragment containing this region, in order to help determine whether tissue-specific expression might be associated with isoforms encoded by a gene family, as it is in mammals. A single sequence (with one ORF) characteristic of Na⁺/K⁺-ATPase was obtained from genomic DNA of each species. Only the fragment from Manduca sexta contained an intron, but at a location different to that found in mammals. For all Diptera so far characterized, the species phylogeny is the same as the α-subunit gene phylogeny (based on the sequences of the first extracellular domain and flanking transmembrane domains). The results strongly indicate a single, ouabain-sensitive isoform of the α-subunit of Na⁺/K⁺-ATPase is present in Diptera.     

99Tcm-MDP SPECT/CT融合显像诊断骨纤维异常增殖症

目的 探讨⁹⁹Tc^m-MDP SPECT/CT融合显像诊断骨纤维异常增殖症（FD）的临床应用价值。方法 回顾性分析13例FD患者的临床和⁹⁹Tc^m-MDP SPECT/CT融合显像资料,其中11例经病理证实为FD,2例经随访确诊。所有患者均有原发肿瘤病史。结果 13例FD均为单发,位于颅面骨10例,位于肋骨、坐骨及胫骨骨干各1例。全身骨显像定性诊断准确率为38.46%（5/13）,SPECT/CT断层融合显像定性诊断准确率为69.23%（9/13）;92.31%（12/13）的患者全身骨显像表现为中-高代谢;CT征象中,磨玻璃密度影（GGO）和骨质膨胀分别占84.62%（11/13）和76.92%（10/13）,溶骨性破坏、硬化边分别占53.85%（7/13）、30.77%（4/13）,13例均未见骨皮质破坏。结论 ⁹⁹Tc^m-MDP SPECT/CT断层融合显像可综合提供功能和解剖学信息,有助于FD的诊断。骨显像中-高代谢及GGO和骨质膨胀的CT征象常提示FD。     

维生素A+玉屏风颗粒+沙美特罗替卡松治疗儿童支气管哮喘的临床效果

目的 探讨维生素A+玉屏风颗粒+沙美特罗替卡松治疗儿童支气管哮喘的临床效果.方法 选取2019年1月至2020年12月我院收治的80例支气管哮喘患儿为研究对象,按照随机数字表法将其分为对照组和研究组,各40例.对照组予以沙美特罗替卡松治疗,研究组在对照组基础上加用维生素A软胶囊与玉屏风颗粒治疗.比较两组患儿治疗前、后的...     

产前丘脑水平横断面超声观察孕11~13^(+6)周胎儿中脑导水管及其与头臀径的关系北大核心CSCD

目的观察丘脑水平横断面超声评估孕11~13^(+6)周胎儿中脑导水管及其与头臀径的关系的价值。方法选取216名孕妇,并根据孕周将其分为3组:A组(n=50)孕11~11^(+6)周,B组(n=103)孕12~12^(+6)周,C组(n=63)孕13~13^(+6)周;并于胎儿丘脑水平横断面超声观察中脑导水管及与头臀径的关系。结果216胎中,204胎(A组45胎、B组99胎、C组60胎)中脑导水管显示良好,产前超声检查胎儿中枢神经系统均未见明显异常,且各组显示率差异无统计学意义(χ^(2)=2.507,P=0.286);12胎中脑导水管显示不清,其中10胎未见明显中枢神经系统异常,梗阻性脑积水、开放性脊柱裂合并脑积水各1胎,后均终止妊娠,胎儿尸体解剖检查结果与产前超声检查结果一致。214例出生后中枢神经系统相关检查均未见明显异常。相关性及回归分析显示胎儿中脑导水管左右径与头臀径呈线性负相关(r=-0.168,P<0.05)。结论于丘脑水平横断面超声观察孕11~13周^(+6)胎儿中脑导水管及与头臀径的关系可为预测胎儿中枢神经系统结构异常提供参考依据;胎儿中脑导水管显示不清提示存在中枢神经系统异常风险。     

Exclusion of 5-HT2A and 5-HT2C Receptor Genes as Candidate Genes for Migraine

Several lines of investigation suggest that the serotonergic system may be involved in the pathogenesis of migraine. In particular, drugs which block 5-HT₂ receptor subtypes appear to be effective migraine prophylactic agents. Therefore, chromosomal DNA regions overlapping the 5-HT_2A (13q14-q22) and 5-HT_2c (Xq22-25) receptor loci were analyzed for possible linkage to the clinical diagnosis of migraine. No evidence for linkage to either chromosomal region was found, although a small subset of migrainous families showed positive likelihood of odds (LOD) scores. However, a homogeneity (HOMOG) analysis provided no statistical evidence for locus heterogeneity. The coding region of the 5-HT_2A and 5-HT_2c receptor genes was also analyzed in migraine patients and unaffected controls using polmerase chain reaction and direct sequencing. No mutations were found in the deduced amino acid sequence of either receptor in the sample of migraineurs tested. These results indicate that DNA-based mutations in the 5-HT_2A and 5-HT_2c receptors are not generally involved in the pathogenesis of migraine.     

第11~13周胎儿额上颌角的二维及三维超声测量

目的 比较及评价二维和三维超声在测量胎儿额上颌(FMF)角中的作用.方法 分别应用二维及三维超声方法在颜面正中矢状面测量11～13周正常胎儿的FMF角,比较两种测量方法所得测值的差异及可重复性,分析三维测量的FMF角与胎儿头臀长(CRL)的关系.结果 共37名胎儿测得FMF角.随CRL增大,测量例数增加,而FMF角减小.其中18名(48.65%)得到符合要求的二维测量平面,30名(81.08%)胎儿获得符合要求的三维重建平面.对同一胎儿,二维测量平面两次测值间的平均差异为2.78°±1.95°,明显大于三维重建平面两次测值间的平均差异(1.68°±1.01°,P<0.01).11名胎儿同时应用两种方法进行测量,所得FMF角差异无统计学意义.三维重建平面测得的FMF角随CRL的增加而减小,二者明显相关(r＝-0.540,P<0.01).结论 在 11～13周正常胎儿中,与二维超声相比,应用三维超声可以快速而精确地测量FMF角.     

Abnormal Na+-K+ ATPase kinetics in a subset of essential hypertensive patients

We have performed a kinetic analysis of the interaction of Na+-K+ ATPase with internal Na+ in erythrocytes of 30 normotensive controls and 72 essential hypertensive patients. Neither the maximal rate of ouabain-sensitive sodium efflux (Vmax) nor the internal Na+ content required for half-maximal stimulation (K50%) were significantly different between normotensive and hypertensive patients. Nevertheless, using the 95% confidence limits of the K50% in the normotensive group as a cut-off point, 13 (18.06%) essential hypertensive patients exhibited increased values of this parameter (29.16 +/- 4.31 mmol l-1 cells) revealing decreased affinity of Na+-K+ ATPase for internal Na+ (Pump-hypertensives). The Vmax was also higher in the Pump '-' subset (14.08 +/- 4.85 mmol (1 cells h)-1 vs. 6.92 +/- 1.80; P = 0.0002) and 10 of these 13 hypertensives exhibited a Vmax above the upper end limit of 10.5 mmol (1 cells h)-1, suggesting a compensatory effect. No differences were observed between the Pump '-' subset and the remaining 59 hypertensives without Na+-K+ pump abnormality when basal erythrocyte Na+ content and clinical parameters of hypertension were examined. Decreased apparent affinity of Na+-K+ pump for internal Na+ present in 9-27% of essential hypertensives may be implicated in pathogenetic mechanisms of hypertension.     

Erythrocyte Na+-H+ exchanger and Na+-Li+ countertransport activity in primary aldosteronism

Abstract. Several authors have described increased Na-H exchanger activity in essential hypertension but no data are available in secondary forms of hypertension such as primary aldosteronism. We measured Na-H exchanger kinetics together with Na-Li countertransport V _max in the erythrocytes of eight patients with primary aldosteronism and in 15 normotensive control subjects. Plasma aldosterone, plasma renin and plasma potassium were also evaluated. Na-H exchanger V _max appear to be increased in patients with primary aldosteronism and Hill's n , an index of co-operativity amongst intracellular proton binding sites, was significantly lower in patients than in controls. No statistically significant differences were found between affinity for intracellular protons (K50%) and for Na-Li countertransport V _max between the two groups studied. We were unable to find any correlations between Na-H exchanger V _max and Na-Li countertransport V _max in the two groups considered as a whole. From the present data Na-H exchanger overactivity would not appear to be a specific feature of essential hypertension but seems to be characteristic in patients with primary aldosteronism.