雌激素受体基因多态性与女性类风湿关节炎相关性的研究

目的分析雌激素受体(ER)基因XbaⅠ和PvuⅡ酶切多态性在女性类风湿关节炎(RA)中的分布,探讨其与人类白细胞抗原(HLA)-DRβ1*04基因亚型、类风湿因子(RF)以及RA患者临床表现的关系。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术,对81例女性RA患者和146名女性正常对照者的ER基因(XbaⅠ、PvuⅡ位点)进行分型,并计算基因分布频率。分析患者的HLA-DRβ1*04基因亚型、RF以及临床表现与ER基因多态性之间的关系。结果女性RA患者的ER基因X、P基因频率均明显高于健康对照组,ER基因的XX和PP基因亚型的阳性率分别高于正常对照组(P<0.05)。而RA患者的xx基因亚型的阳性率明显低于健康对照组(P<0.05)。RA患者XXPP基因型的阳性率明显高于健康对照组,而xxpp基因型的阳性率明显低于健康对照组(P<0.05)。携带PP基因型的RA患者HLA-DRβ1*04基因亚型的阳性率明显升高(P<0.05)。ER基因中pp基因型、XXpp和xxPP基因型的患者关节受累数明显增高(P<0.05)。结论女性RA患者ER基因的X和P的基因频率表达明显增高。ER基因酶切多态性分析中,XX、PP及XXPP基因型可能与女性RA的易感性相关。PP基因型可能与HLA-DRβ1*04基因有一定的相关性,pp基因型、XXpp和xxPP基因型可能与RA关节病变的程度相关。     

Association of IL-8 gene polymorphisms with non small cell lung cancer in Tunisia: A case control study

Interleukin 8 (IL-8), is a proinflammatory chemokine, has been reported to have angiogenic activity and to be responsible for tumor-associated angiogenesis in several cancers. In this study, we aimed to study the (IL-8) gene polymorphism in relation with risk development of non small cell lung cancer in Tunisian patient. Two single nucleotide polymorphisms (−251T/A [rs4073], +781C/T [rs2227306]) of the IL-8 gene were screened in 170 patients with NSCLC and 225 healthy controls by PCR–RFLP.     

用分子生物学技术分析国内六株旋毛虫分离株

本文首次对来自我国不同地区、不同宿主来源有代表性的6个旋毛虫分离株从基因组DNA的限制性酸切长度多态性、同工酶及可溶性蛋白进行综合研究。核酸结果显示：长春株与其余各地域株的限制性酶切困话间存在着差异，用长春株特异性DNA片段（1．12kb）制成探针，与各株DNA进行Southern杂交，发现各虫株的杂交带型不一，且仅长春株出现1．12kb杂交带。同工酶结果显示：长春株与其余各珠在5种同工酶（GPI、G6PD、HK、6PGDH及AK）酶谱中有显著不同。等电聚焦电泳结果显示：长春株具有一条约4.1PI的特异带。上述结果提示：我国6株旋毛虫分离株间存在着差异，长春株与其余各株差异显著，从而推断我国旅毛虫虫株至少存在2种不同的生物学类型，其间的差异主要与不同的地理分布和／或不同宿主来源有关。     

A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis

Summary Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA1^*0501) and DQA1.8 (DQA1^*0401, ^*0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA.Most of the data covered in this article are from the doctoral thesis of Haas [39]. Supported by SFB 217 To whom ffprint requests should be sent     

CYP2D6*10基因多态性与美托洛尔治疗高血压疗效的关系 (英文)

目的：研究CYP2D6＊10基因多态性与美托洛尔治疗高血压疗效的关系。方法：60例原发性高血压患者口服美托洛尔47.5 mg/d三日后,测定口服美托洛尔2h 的血药浓度。应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测CYP2D6＊10基因型,根据基因检测结果高血压病人被分为 CC型组（野生型纯合子,快代谢型,14例）,CT型组（突变杂合子,中代谢型,25例）和 TT型组（突变纯合子,弱代谢性,19例）3组。根据CYP2D6＊10基因型调整美托洛尔用量,一周后,再次检测口服美托洛尔2h的血药浓度,并检测基因导向治疗前后的平均心率及血压。结果：基因导向治疗前,美托洛尔血药浓度 TT组显著高于 CC和 CT组[（64.74±32.94）ng/ml比（26.57±19.40）ng/ml比（23.88±12.86）ng/ml,P＜0.01];与 TT组比较,CC组平均收缩压[（132.84±13.40）mmHg比（144.14±14.28）mmHg]、舒张压[（76.95±9.07）mmHg比（81.36±7.33） mmHg]、心率[（69.13±11.83）次/min比（76.66±7.33）次/min]明显升高（P 均＜0.05）。基因导向治疗后各组的血药浓度、平均收缩压、舒张压及心率无统计学差异（P 均＞0.05）。与基因导向治疗前比较,CC组治疗后血药浓度显著升高,平均收缩压、舒张压及心率显著降低（P＜0.05）, CT组、TT组的血压及心率与治疗前比较无统计学差异（P＞0.05）。结论：CYP2D6＊10基因多态性影响美托洛尔药物代谢及其治疗高血压病的疗效,基因导向个体化治疗可显著改善疗效,短时间内达到理想治疗目标。     

CYPl7、CYPlA2酶基因多态性与子宫内膜异位症的关系

目的探讨CYPl7 T-34C、CYPIA2 G-2964A基因多态性与子宫内膜异位症遗传易感性的关系。方法抽取108例确诊为子宫内膜异位症患者及84例对照组女性的静脉血,提取全基因组DNA,分别用聚合酶链式反应（PCR）技术扩增CYPl7 T-34C、CYPIA2 G-2964A多态位点的基因片段,并对其进行酶切,根据酶切结果计算出各等位基因的表型频率,用X2检验及OR值分析其多态性与子宫内膜异位症的关系。结果病例组和对照组CYPl7基因的基因型及等位基因的频率分布比较差异有统计学意义（P〈O.05）。病例组和对照组CYPIA2基因型、等位基因频率的比较差异无统计学意义（P〉0.05）。结论CYPl7 T-34C可能与III、IV期子宫内膜异位症发病风险相关。CYPlA2 G-2964A多态性可能不是子宫内膜异位症独立的危险因素。     

胚胎碎片对妊娠临床结局及去除后对胚胎发育的影晌

目的观察胚胎碎片对胚胎移植后的临床结局的影响,以及去除碎片对含碎片的胚胎发育影响。方法回顾性分析2012年新鲜IVF周期移植至少一个≥10％碎片的胚胎与移植完全无碎片胚胎临床结局,及2012年3月～5月IVF周期患者O／1PN优质胚胎,观察胚胎碎片去除组、胚胎碎片组及无碎片组的胚胎发育情况。结果含胚胎碎片组的临床妊娠率及种植率显著低于无碎片组,差异有显著性意义;去除碎片组与未去除碎片组的囊胚形成率与无碎片组,差异无显著性意义。结论胚胎碎片影响胚胎的种植;去除胚胎碎片不能显著改善胚胎的发育潜能。     

Fragment‐ and negative image‐based screening of phosphodiesterase 10A inhibitors

A novel virtual screening methodology called fragment‐ and negative image‐based (F‐NiB) screening is introduced and tested experimentally using phosphodiesterase 10A (PDE10A) as a case study. Potent PDE10A‐specific small‐molecule inhibitors are actively sought after for their antipsychotic and neuroprotective effects. The F‐NiB combines features from both fragment‐based drug discovery and negative image‐based (NIB) screening methodologies to facilitate rational drug discovery. The selected structural parts of protein‐bound ligand(s) are seamlessly combined with the negative image of the target's ligand‐binding cavity. This cavity‐ and fragment‐based hybrid model, namely its shape and electrostatics, is used directly in the rigid docking of ab initio generated ligand 3D conformers. In total, 14 compounds were acquired using the F‐NiB methodology, 3D quantitative structure–activity relationship modeling, and pharmacophore modeling. Three of the small molecules inhibited PDE10A at ~27 to ~67 μM range in a radiometric assay. In a larger context, the study shows that the F‐NiB provides a flexible way to incorporate small‐molecule fragments into the drug discovery.     

肺泡灌洗液LDH、CYfra21-1、PCT水平联合检测诊断肺癌临床价值探讨

目的探讨肺泡灌洗液(BALF)中乳酸脱氢酶(LDH)、细胞角蛋白19片段(CYfra21-1)、降钙素原(PCT)水平联合检测诊断肺癌的临床价值。方法选取2017年7月～2018年7月我院门诊及住院行电子支气管镜检查的患者98例为疾病组,分为肺癌组(58例)和肺部良性病变组(40例)为研究对象,选取同期收治的体检健康者100例作为健康组,采用酶联免疫法(ELISA)检测所有入组对象术前血清LDH、CYfra21-1和PCT水平,检测疾病组肺泡灌洗液中LDH、CYfra21-1和PCT水平,分析肺泡灌洗液中的LDH、CYfra21-1和PCT单独和联合检测在诊断肺癌中的意义。结果疾病组血清LDH、CYfra21-1和PCT水平均高于健康组(P0.05);肺癌组血清LDH、CYfra21-1和PCT水平高于肺部良性病变组(P0.05);肺癌组BALF中LDH、CYfra21-1和PCT水平均高于肺部良性病变组。ROC曲线分析显示,BALF的LDH、CYfra21-1和PCT联合检测肺癌的曲线下面积(AUC)为0.866,高于血清中LDH、CYfra21-1和PCT三者联合检测AUC为0.753。结论相比于血清指标,BALF中的LDH、CYfra21-1和PCT联合可以为肺癌患者提供更准确的诊断。