TSH受体基因突变与毒性多结节性甲状腺肿的相关性

从16例毒性多结节性甲状腺肿(TMG)患者的甲状腺结节组织提取DNA，经PCR后对PCR产物测序，发现TSH受体基因有3例点突变(A1964T)和2例插入性突变(在1928位核苷酸之后插入一个G)，推测这些突变在TMG发病中可能起重要作用。     

TSHR基因突变与亚临床型毒性多结节性甲状腺肿的相关研究

目的 探讨TSH受体(THSR)基因突变在亚临床型毒性多结节性甲状腺肿(STMG)发病中的作用。方法 9例STMG患者和9例非毒性结节性甲状腺肿(nTMG)患者．手术切除肿大的甲状腺组织．用酚-氯仿-异戊醇法提取基因组DNA，对目的基因片段进行聚合酶链反应(PCR)及DNA测序。结果 在9例STMG患者中，发现3例单碱基插入性突变．在1950位和1951似核酸之间插入了一个胞嘧啶(C)．使616位以后氨基酸发生了移码突变，9例nTMG未发生基因突变。结论 TSHR基因突变可能在STMG形成中发挥重要作用。     

促甲状腺激素受体基因突变致毒性多结节性甲状腺肿的研究进展

毒性多结节性甲状腺肿(TMG)是继发性甲状腺功能亢进症(简称甲亢)的一种,病人先有结节性甲状腺肿大多年.以后才出现甲亢症状.肿大腺体呈结节状.往往为多发,两侧多不对称.功能结节多表现为自主性和高功能性,无眼球突出,容易发生心肌损害,年龄多在4|D岁以上,在我国发病有增高趋势,且多发生于我国北方[1].     

促甲状腺激素受体胞外段基因突变与Graves病的相关研究

Ｇｒａｖｅｓ病 (ＧＤ)是一种器官特异性自身免疫性甲状腺疾病 ,患者体内存在着多种自身抗体 ,ＧＤ的发病中以促甲状腺激素受体抗体 (ＴＲＡｂ)最为重要 ,而ＴＲＡｂ所对应的抗原是ＴＳＨ受体 (ＴＳＨＲ)。国外有学者报道ＧＤ的发生与ＴＳＨＲ基因突变有关 ,但另有学者认为与ＴＳＨＲ基因突变无关。本研究探讨中国人Ｇｒａｖｅｓ病的发病与ＴＳＨＲ基因突变之间的关系。一、对象和方法1.对象 :病例组 :ＧＤ患者 5 0例 (男 5 ,女 4 5 ) ,年龄 19～5 7岁 ,有典型的ＧＤ症状和体征 ,血清ＴＴ3 、ＴＴ4、ＦＴ3 、ＦＴ4升高 ,ＴＳＨ降低 ,均经病…     

毒性结节性甲状腺肿的外科治疗(附66例报告)

目的总结毒性结节性甲状腺肿的治疗体会。方法对1990～2006年收治的66例毒性结节性甲状腺肿行手术治疗的临床资料进行回顾性分析。结果66例中42例采用硫脲类药物加碘剂进行术前准备,10例采用心得安加碘剂准备,14例单用碘剂准备。除1例病人因甲状腺癌外都采用甲状腺次全切除术,术后无甲状腺危象,无永久性喉返神经损伤及甲状旁腺功能减低等并发症。结论手术治疗毒性甲状腺肿是安全有效的,须行合理的术前准备及选择适当的手术方式。     

促甲状腺激素受体胞内环基因突变与乳头状甲状腺癌发病的相关性研究

目的探讨乳头状甲状腺癌的发病与促甲状腺激素受体(TSHR)基因突变的相关性。方法采用巢氏-多聚酶联反应-单链构象多态性分析(NEST-PCR-SSCP)和DNA测序方法,对65例乳头状甲状腺癌和44例正常甲状腺组织TSHR3个胞内环基因进行检测。结果NEST-PCR-SSCP检测乳头状甲状腺癌促甲状腺激素受体(TSHR)3个胞内环未发现明显带型异常;DNA测序后,检测的第3胞内环2例对照组织和3例甲状腺癌组织TSHR2000位点碱基均由C→T,使得所编码的601位氨基酸由组氨酸(CAT)→酪氨酸(TAT)(His→Tyr),余胞内环未发现基因突变。结论乳头状甲状腺癌TSHR3个胞内环未发现基因突变,提示乳头状甲状腺癌发病与TSHR胞内环基因突变无关;5例标本601位氨基酸均为酪氨酸,考虑中国人TSHR基因可能与国外人群存在差异,TSHR2000位点碱基存在基因多态性。     

TSH受体基因SNP与Graves病、桥本甲状腺炎和结节性甲状腺肿之间的相关性研究

目的　探讨TSH受体基因单核苷酸多态性 (SNP)与甲状腺疾病〔包括Graves病 (GD) ,结节性甲状腺肿 ,桥本甲状腺炎 (HT)〕有无相关性。方法　以 60例有甲状腺疾病家族史患者 (其中 3 0例GD、10例HT、2 0例结节性甲状腺肿患者 ) ,48例散发Graves病患者及 96名健康对照者作为研究对象 ,采用外周血白细胞抽提DNA ,设计引物 ,PCR扩增 ,对扩增产物纯化后测序。结果患者中共发现 8个多态位点 ,其中第8外显子上的多态位点 (E8A 40C)在SNP库中未见报道 ,为首次发现 ;将这些多态位点基因型变化与正常组比较 ,无明显统计学差异。结论　本研究提示汉族人TSH受体基因与这几种甲状腺疾病无相关性 ;该基因的多态位点在不同的人种间存在明显差异。     

MTB对阿米卡星和卡那霉素耐药相关rrs与eis基因突变的研究

本研究搜集了吉林省全部9个地级市结核病医疗机构2014—2017年内1357株结核分枝杆菌分离株。采用比例法进行Am和Km的药物敏感性试验,并对rrs和eis基因进行PCR和测序分析。发现28株同时耐Km和Am,单耐Km者有2株; 其中26株MTB的rrs基因均发生突变,基因突变率为92.86%;6株菌存在eis基因突变,突变率为21.43%。60株对照株未发现基因突变。吉林省MTB对Am和Km存在较高的交叉耐药现象;rrs基因的突变可以作为两者交叉耐药的分子标志,为建立耐Am和(或)Km结核病快速检测技术提供分子基础。     

表皮生长因子受体基因突变在晚期非小细胞肺癌二线治疗中作用的研究

目的 探讨表皮生长因子受体(EGFR)基因突变在晚期非小细胞肺癌(NSCLC)二线治疗中的指导意义.方法 对2005年12月至2009年12月住我院的139例既往至少接受过1次含铂化疗且最近1次化疗后肿瘤进展或复发的NSCLC的病理组织行EGFR基因检测,根据检测的结果把患者分为EGFR突变型口服吉非替尼组(31例)和EGFR野生型口服吉非替尼组(50例)及EGFR野生型口服吉非替尼组(50例).对3组患者进行临床特征、病理、疗效、生存期、体力状况评分(PS)、毒副反应及生活质量的分析.结果 女性、腺癌、非吸烟者的EGFR突变率高于对应组;突变型吉非替尼组、野生型吉非替尼组(62.0%,31例)和野生型多烯紫杉醇组中位无进展生存期(分别为2.8、2.0和2.5个月)、中位生存时间(分别为8.9、7.1和7.8个月)比较,差异有统计学意义(H值分别为11.198、16.991,均P＜0.01).突变型吉非替尼组、野生型吉非替尼组PS评分的变化分别为96.8%(30例)和62.0%(31例),差异有统计学意义(x2=12.583,P＜0.01).野生型吉非替尼组(62.0%,31例)和野生型多烯紫杉醇组(66.0%,33例)化疗PS评分变化比较,差异无统计学意义(x2=0.878,P＞0.05).结论 表皮生长因子受体基因突变可作为指导晚期NSCLC二线治疗的重要指标.

Abstract：

Objective To explore the effect of gene mutations of epidermal growth factor receptor ( EGFR) on targeting therapy of advanced non-small cell lung cancer (NSCLC). Methods The 139 hospitalized patients who had been treated at least once with platinum-based chemotherapy and had tumor progression or recurrence after the last chemotherapy between December 2005 and December 2009, underwent EGFR gene test extracted from the pathological tissues. Based on the results of the test, the patients were divided into three groups: EGFR mutation per os (p.o.)Gefitinib (MPG) group, wild-type EGFR per os (p. o. ) Gefitinib (WpG) group and wild-type EGFR post-docetaxel chemotherapy (WpD) group. Clinical characteristics, pathology, treatment efficacy,survival time, performance status (PS) score, adverse reaction and quality of life of patients in the three groups were assessed. Results The EGFR mutation rate were higher in female, patients with adenocarcinoma and non-smokers than in male, smokers and those without adenocarcinoma. There were significant differences in median progression-free survival and median survival time among the three groups, which were 2.8 and 8. 9 months in MpG group, 2.0 and 7.1 months in WpG group,2.5 and 7. 8 months in WpD group(H=11. 198, 16. 991 ,all P＜0.01). The changes of PS score were significantly different between MpG group and WpG group (96. 8% vs. 62. 0%, x2 = 12. 583 ,P＜0. 01 ). However, there was no difference in changes of PS score between WpG group and WpD group (62. 0% vs. 66. 0%, x2 =0. 878,P＞0. 05). Conclusions The gene mutation of epidermal growth factor receptor may be served as an important indicator of advanced non-small cell cancer therapy.     

结核分枝杆菌DNA促旋酶基因突变与耐氟喹诺酮类药物的相关性研究

目的 分析MDR TB结核分枝杆菌临床分离株的DNA促旋酶（gyr）基因突变特点,初步探究MDR-TB对氟喹诺酮类药物耐药与gyr基因突变的相关性.方法 采用最低抑菌浓度（MIC）法筛选MDR-TB,对17株临床MDRTB菌株应用DNA直接测序法检测gyr基因的突变情况,分析细菌基因突变与耐药产生的相关性.结果 Mtb 1株标准菌株（H37Rv）未见gyr A亚单位基因（gyrA）和gyr B亚单位基因（gyrB）基因突变,所有17株临床菌株gyrA均存在95位AGC→ACC.12株耐环丙沙星和左氧氟沙星菌株中,10株gyrA产生了错义突变,突变率为83.3％;突变位点位于89位、90位、91位和94位;1株发生了gyrB突变,突变位点位于500位.耐莫西沙星的9株耐药株中,8株gyrA发生突变,占88.9％.结论 gyrA基因突变是Mtb对氟喹诺酮类药物产生耐药的机制之一;gyrA的错义突变主要发生在第89位、90位、91位、94位密码子上.     

Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter

Toxic multinodular goiter, a heterogeneous disease producing hyperthyroidism, is frequently found in iodine-deficient areas. The pathogenesis of this common clinical entity is still unclear. The aim of the present study was to search for activating TSH receptor (TSHr) or Gs alpha mutations in areas of toxic or functionally autonomous multinodular goiters that appeared hyperfunctioning at thyroid scintiscan but did not clearly correspond to definite nodules at physical or ultrasonographic examination. Surgical tissue specimens from nine patients were carefully dissected, matching thyroid scintiscan and thyroid ultrasonography, to isolate hyperfunctioning and nonfunctioning areas even if they did not correspond to well-defined nodules. TSHr and Gs alpha mutations were searched for by direct sequencing after PCR amplification of genomic DNA. Only 2 adenomas were identified at microscopic examination, whereas the remaining 18 hyperfunctioning areas corresponded to hyperplastic nodules containing multiple aggregates of micromacrofollicules not surrounded by a capsule. Activating TSHr mutations were detected in 14 of these 20 hyperfunctioning areas, whereas no mutation was identified in nonfunctioning nodules or areas contained in the same gland. No Gs alpha mutation was found. In conclusion, activating TSHr mutations are present in the majority of nonadenomatous hyperfunctioning nodules scattered throughout the gland in patients with toxic or functionally autonomous multinodular goiter.     

弥漫性甲状腺肿治疗前后心率变异性的变化

目的 探讨弥漫性甲状腺肿（又称Graves病,简称GD）患者心率变异性（HRV）的变化。方法 选取30例GD患者,另选取30例健康志愿者作为对比研究。观察GD患者治疗前后HRV指标：所有窦性心搏RR间期标准差（SDNN）、全程记录中每5 min窦性心搏RR间期平均值的标准差（SDANN）、相邻RR间期差大于或等于50 ms的个数占总心跳次数的百分比（PNN50）、低频LF（0. 04 ~ 0. 15 Hz）、高频HF（0. 15 ~ 0. 40 Hz）、LF/ HF值、极低频VLF（0. 003 3 ~0. 04 Hz）。结果 GD组治疗后与治疗前相比,时域指标：SDNN、RMSDNN、SDANN、PNN50均改善（P 均〈0. 01）;频域指标LF、HF、VLF亦均明显改善（P 均〈0. 01）;GD组治疗前HRV指标：SDNN、PNN50、LF、HF、VLF均低于对照组（P〈0. 01）;GD组治疗后与对照组相比,HRV上述指标两组无显著性差异。 GD组治疗前频域指标24 h波动曲线趋于平稳,治疗后波动性有所恢复。结论 GD患者存在心脏自主神经调节功能异常,以迷走神经受损为主;24 h频域指标波动性则趋于平稳,治疗后调节功能异常和波动性可有不同程度恢复。     

An outline concerning the potential use of recombinant human thyrotropin for improving radioiodine therapy of multinodular goiter

Radioiodine ((131)I) treatment for nontoxic and toxic multinodular goiter (MNG) is an alternative therapeutic procedure used especially for patients with contraindication for surgery. Several studies have been conducted in recent years assessing the use of recombinant human TSH (rhTSH) in increasing (131)I uptake in MNGs. This procedure also decreases the activity level of the administered (131)I, changes the distribution of (131)I in the thyroid, lowers the absorption dose, and dramatically reduces the volume of the goiter (50-75% of the baseline volume). A major disadvantage, however, is the induction of hypothyroidism in a relatively large number of patients. A transient increase in thyroid volume and tenderness was noted in the first week of treatment. Also a short period (2-4 weeks) of hyperthyroidism was observed in most patients with potential consequences particularly for the elderly. Still, there has been no evidence to date that the adverse effects outweigh the positive results of using rhTSH. The use of rhTSH in benign goiter disease has not yet been approved worldwide, but its positive activity in MNG is remarkable and promising.     

Sporadic nonautoimmune neonatal hyperthyroidism due to A623V germline mutation in the thyrotropin receptor gene

Neonatal hyperthyroidism is a rare disorder and occurs in two forms. An autoimmune form is associated with maternal Graves' disease, resulting from transplacental passage of maternal thyroid-stimulating antibodies and a nonautoimmune form is caused by gain of function mutations in the thyrotropin receptor (TSHR) gene. Thyrotoxicosis caused by germline mutations in the TSHR gene may lead to a variety of clinical consequences. To date, 55 activating mutations of the TSHR gene have been documented. Fourteen cases with sporadic activating TSHR germline mutations have been described. Here we report a male infant with nonautoimmune hyperthyroidism due to an activating germline TSHR mutation (A623V), whose clinical picture started in the newborn period with severe hyperthyroidism. His parents did not have the same mutation. This mutation had been previously detected as a somatic mutation in patients with toxic adenomas. This is the first report of a sporadic case of nonautoimmune congenital hyperthyroidism associated with A623V mutation.     

浙江地区汉族人线粒体DNA ND1基因T3394C突变与老年2型糖尿病

目的 探讨线粒体DNA ND1基因T3394C突变与老年2型糖尿病的关系. 方法 采用聚合酶链反应(PCR)产物直接测序法对340例无血缘关系的2型糖尿病患者(其中老年糖尿病组90例,非老年糖尿病组250例)和265例健康对照者(老年健康对照组130例,非老年健康对照组135例)的血细胞线粒体DNA进行突变位点检测,并用DNASTAR和Antheprot 5.0软件分析突变位点. 结果 老年糖尿病组、老年健康对照组和非老年糖尿病组分别检出5例、1例和2例T3394C突变.T3394C突变在老年糖尿病组和老年健康对照组之间分布差异有统计学意义(P＜0.05),在老年糖尿病组和非老年糖尿病组之间分布差异也有统计学意义(P＜0.05).蛋白质结构预测显示T3394C突变引起ND1蛋白二级结构改变. 结论 线粒体DNA ND1基因T3394C突变可能与老年2型糖尿病的发生有关.     

自身免疫性甲状腺病与促甲状腺激素受体基因突变的关系

自身免疫性甲状腺病（AITD）是一组器官特异性自身免疫疾病。主要包括Graves病（GD）、桥本甲状腺炎（HT）和原发性粘液性水肿。促甲状腺激素受体（TSHR）是AITD发病中重要的自身抗原,对其遗传变异的研究具重要意义。人类TSHR基因位于染色体14q31处,全长60kb,包括10个外显子和9个内含子,第1至9号外显子编码TSHR氨基酸膜外区的部分,跨膜区和膜内区部分由第10号外显子编码。研究表明,自主性功能性甲状腺腺瘤,遗传或散发性毒性甲状腺增生症,先天性甲减等多种甲关腺疾病与TSHR基因突变密切相关,对于Graves病和桥本甲状腺炎,这方面的研究较少。目前有G205C体细胞突变,C253A原始细胞突变的报道,但尚存争议。本研究初步探讨AITD与TSHR基因突变的关系。     

家族性高胆固醇血症患者低密度脂蛋白受体基因新突变一例

目的 分析中国家族性高胆固醇血症（FH）患儿低密度脂蛋白受体（LDL－R）基因突变的情况，并为在婴幼儿时期此病的症前筛查提供确诊方法。方法 以患儿及其父母的基因组DNA为模板，首先用聚合酶链反应（PCR）扩增该基因的启动子和全部18个外显子，然后用单链构象多态性（SSCP）方法分析PCR产物，最后对电泳结果异常进行DNA测序。结果 在1个家系中检测出患儿和其父亲LDL－R基因的一种新突变，即在第4外显子的444位碱基发生杂合突变（T→A），相应的氨基酸由半胱氨酸变成终止密码子，其母亲LDL－R基因正常。结论 LDL－R基因此位点的突变可引起FH，PCR－SSCP方法可用于筛查出的高危人群的确诊。     

家族性高胆固醇血症患者低密度脂蛋白受体基因新的突变类型一例

目的：分析一例家庭性高胆固醇血症患的低密度脂蛋白受体基因突变位点。方法：以患儿的基因组DNA为模板，用聚合酶链反应（PCR）扩增该基因的18个外显子。用单链构象多态性（SSCP）方法分析检测PCR产物，对电泳结果异常进行DNA测序。结果：单链构象多态性分析发现患儿第10外显子存在一异常条带。DNA测序证实患儿第10外显子发生N515S纯合错义突变。结论：该病例为一个新的LDLR突变位点；聚合酶链反应－单链构象多态性分析（PCR－SSCP）可用于该突变位点的诊断。