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1卒中或短暂性脑缺血发作患者的卒中预防指南 美国心脏协会/美国卒中协会为医疗卫生专业人员制定的指南显示文摘本指南旨在为缺血性卒中或短暂性脑缺血发作存活患者的卒中预防提供全面和及时的循证推荐,包括危险因素的控制、动脉粥样硬化性疾病的于预、心源性栓塞的抗栓治疗以及非心源性栓塞性卒中的抗血小板治疗。另外,还对其他许多特殊情况下的复发性卒中预防提供了推荐意见,包括动脉夹层分离、卯圆孔未闭、高同型半胱氨酸血症、高凝状态、镰状细胞病、脑静脉窦血栓形成、女性卒中(尤其是与妊娠和绝经后雌激素替代治疗相关性卒中)、脑出血后抗凝药的使用等,以及实施本指南及其在高危人群中应用的特定方法。Karen L. Furie Scott E. Kasner Robert J. Adams Gregory W. Albers Ruth L. Bush Susan C. Fagan Jonathan L. Halperin S. Claiborne Johnston Irene Katzan Walter N. Kernan Pamela H. Mitchell Bruce Ovbiagele Yuko Y. Palesch Ralph L. Sacco Lee H. Schwamm Sylvia Wassertheil-Smoller Tanya N. Turan Deidre Wentworth 李海峰(译) 刘涛(译) 杨潘(译) 王鹏(译) 2011国际脑血管病杂志2011,19,1:391
2卒中和短暂性脑缺血发作患者的卒中预防指南美国心脏协会/美国卒中协会为医疗卫生专业人员制定的指南显示文摘本更新版指南旨在为缺血性卒中或短暂性脑缺血发作存活者的卒中预防提供全面和及时的循证推荐.本指南适用于所有为上述患者提供二级预防的临床医生.这些循证推荐包括危险因素的控制、血管闭塞的干预、心源性栓塞的抗栓治疗以及非心源性栓塞性卒中的抗血小板治疗.还对各种特殊情况下复发性卒中的预防提供了推荐意见,包括主动脉弓粥样硬化、动脉夹层分离、卵圆孔未闭、高同型半胱氨酸血症、高凝状态、抗心磷脂抗体综合征、镰状细胞病、脑静脉窦血栓形成以及妊娠.此外,还有专门的章节对颅内出血后抗栓和抗凝治疗的应用以及指南的实施进行了讨论.Walter N.Kernan Bruce Ovbiagele Henry R.Black Dawn M.Bravata Marc I.Chimowitz Michael D.Ezekowitz Margaret C.Fang Marc Fisher Karen L.Furie 洪道俊 黄招君 李小兵 周美鸿 吴成斯 王博 卢艺 吴裕臣 2014国际脑血管病杂志2014,22,11:585
3DNA-PKcs subunits in radiosensitization by hyperthermia on hepatocellular carcinoma hepG_2 cell line显示文摘AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was given at 45.5 ℃Cellsurvival was determined by an in vitro clonogenic assay forthe cells treated with or without hyperthermia at varioustime points. DNA DSB rejoining was measured usingasymmetric field inversion gel electrophoresis (AFIGE). TheDNA-PKcs activities were measured using DNA-PKcs enzymeassay system.RESULTS: Hyperthermia can significantly enhanceirradiation-killing cells. Thermal enhancement ratio ascalculated at 10 % survival was 2.02. The difference inradiosensitivity between two treatment modes manifestedas a difference in the α components and the almost sameβ components, which α value was considerably higher inthe cells of combined radiation and hyperthermia ascompared with irradiating cells (1.07 Gy-1 versus 0.44 Gy1). Survival fraction showed 1 logarithm increase after an8-hour interval between heat and irradiation, whereas DNA-PKcs activity did not show any recovery. The cells wereexposed to heat 5 minutes only, DNA-PKcs activity wasinhibited at the nadir, even though the exposure time waslengthened. Whereas the ability of DNA DSB rejoining wasinhibited with the increase of the length of hyperthermictime. The repair kinetics of DNA DSB rejoining aftertreatment with Wortmannin is different from thehyperthermic group due to the striking high slow rejoiningcomponent.CONCLUSION: Determination with the cell extracts andthe peptide phosphorylation assay, DNA-PKcs activity wasinactivated by heat treatment at 45.5 C, and could notrestore. Cell survival is not associated with the DNA-PKcsinactivity after heat. DNA-PKcs is not a unique factor affectingthe DNA DSB repair. This suggests that DNA-PKcs do notplay a crucial role in the enhancement of cellularradiosensitivity by hyperthermia.Walter J.Curran George Iliakis 2002World Journal of Gastroenterology2002,8,5:87
4Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses:A multicenter study显示文摘AIM:To evaluate the ability of endoscopic ultrasound(EUS) elastography to distinguish benign from malignant pancreatic masses and lymph nodes.METHODS:A multicenter study was conducted and included 222 patients who underwent EUS examination with assessment of a pancreatic mass(n=121) or lymph node(n=101).The classification as benign or malignant,based on the real time elastography pattern,was compared with the classif ication based on the B-mode EUS images and with the fi nal diagnosis obtained by EUS-guided fi ne needle aspiration(EUS-FNA) and/or by surgical pathology.An interobserver study was performed.RESULTS:The sensitivity and specificity of EUS elastography to differentiate benign from malignant pancreatic lesions are 92.3% and 80.0%,respectively,compared to 92.3% and 68.9%,respectively,for the conventional B-mode images.The sensitivity and specificity of EUS elastography to differentiate benign from malignant lymph nodes was 91.8% and 82.5%,respectively,compared to 78.6% and 50.0%,respectively,for the B-mode images.The kappa coefficient was 0.785 for the pancreatic masses and 0.657 for the lymph nodes.CONCLUSION:EUS elastography is superior compared to conventional B-mode imaging and appears to be able to distinguish benign from malignant pancreatic masses and lymph nodes with a high sensitivity,specificity and accuracy.It might be reserved as a second line examination to help characterise pancreatic masses after negative EUS-FNA and might increase the yield of EUS-FNA for lymph nodes.Marc Giovannini Botelberge Thomas Bories Erwan Pesenti Christian Caillol Fabrice Esterni Benjamin Monges Geneviève Arcidiacono Paolo Deprez Pierre Yeung Robert Schimdt Walter Schrader Hanz Szymanski Carl Dietrich Christoph Eisendrath Pierre Van Laethem Jean-Luc Devière Jacques Vilmann Peter Saftoiu Andrian 2009World Journal of Gastroenterology2009,15,13:48
5Update in management of mesenteric ischemia显示文摘肠系膜局部缺血混乱被剥夺一或几个腹的机关遇见新陈代谢的要求足够的呼吸的一个发行量不足事件猛抛。尽管 mes 伤寒局部缺血不经常发生,死亡率从 60% ~ 100% ,依靠阻塞的消息提供者。成功的结果依赖于怀疑和迅速的管理的一个高索引。我们简短考察病理生理学和演讲各种各样是化学家实体并且在诊断和治疗考察当前的现状。尽管有在诊断和治疗的进展,迅速的诊断和支持的照顾为成功的结果仍然保持批评。新成像技术,血管内治疗和新兴的研究可以改进我们的途径到这个致命的条件。Robert W Chang John B Chang Walter E Longo 2006World Journal of Gastroenterology2006,12,20:38
6阿尔泰—阿尔金地学断面地壳结构显示文摘根据阿尔泰—阿尔金地学断面的地震纵、横波资料 ,建立了地壳速度及泊松比结构 .测区的地壳具有明显的三分结构特征 ,其纵波速度自上而下依次为 6 .0~ 6 .3km s、6 .3~ 6 .6km s及 6 .9~ 7.0km s ;阿尔泰南缘的地壳最厚 ,为 5 6km ,准噶尔盆地的地壳最薄 ,为 4 6km ,大部分地区的地壳厚度为 5 0km左右 .准噶尔盆地与天山之间上地幔顶部的纵波速度为 7.7~ 7.8km s ;阿尔泰南缘及塔里木盆地上地幔顶部的纵波速度较高 ,为 7.9~ 8.0km s.测线南部 ,包括东天山及塔里木东缘 ,自地表至 30km深处的地壳纵波速度低 ,泊松比为 0 .2 5 ,表明上地壳主要为石英及花岗质成分 ;而测线北部 (包括阿尔泰及准噶尔盆地 )的中、上地壳则呈现较高的泊松比 (0 .2 6~ 0 .2 7) ,可能为基性地壳的体现 .厚 15~ 30km的下地壳纵波速度 (6 .9~ 7.0km s)较高 ,泊松比为 0 .2 6~ 0 .2 8,可能以镁铁质的麻粒岩成分为主 .位于天山及其南侧地壳中部的低速层 (VP=5 .9km s,σ=0 .2 5 )则可能为晚古生代的构造热事件中的花岗质侵入岩 .王有学 韩果花 姜枚 袁学诚 Walter D Mooney Robert G Coleman 2004地球物理学报2004,47,2:32
7苯丙胺类兴奋剂滥用的治疗研究进展显示文摘江海峰 赵敏 孙海明 王石斌 Walter Ling 2008中国药物依赖性杂志2008,17,4:29
8Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma显示文摘AIM:Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultimately hepatocellular carcinoma (HCC), the mechanism underlying the worsening is still undefined. Experimental infection by Helicobacter hepaticusin mice causes chronic hepatitis and HCC and recently, more Helicobacter species (Helicobacter spp.) have been detected in the liver of patients suffering from cholestatic diseases and HCC arising from non-cirrhotic liver. We investigated whether Helicobacter spp. sequences could be detected in the liver of patients with cirrhosis and HCC compared to subjects with metastasis to liver from colon cancer.METHODS:Twenty-three liver samples from patients operated upon for HCC superimposed on hepatitis C virus (HCV)-related cirrhosis and 6 from patients with resected metastases from colorectal cancer, were tested by polymerase chain reaction for presence of genomic 16S rRNA of Helicobacter genus using specific primers. DNA sequencing and cagA gene analysis were also performed.RESULTS:Genomic sequences of Helicobacter spp. were found in 17 of 20 (85%) liver samples from patients with HCC and in 2 of 6 samples from patients with liver metastasis.In three samples of the first group the result was uncertain.Hpyloriwas revealed in 16 out of 17 positive samples and Helicobacter pullorum in the other.CONCLUSION: Helicobacter spp., carcinogenic in mice,were found at a higher frequency in the liver of patients with HCV-related cirrhosis and HCC than those in patients without primary liver disease.RinaldoPellicano MarioRizzetto AntonioPonzetto Vincenzo Mazzaferro Walter Franco Grigioni MiguelAngelCutufia SharmilaFagoonee LorenzoSilengo 2004World Journal of Gastroenterology2004,10,4:28
9Acupuncture for irritable bowel syndrome: A blinded placebo-controlled trial显示文摘AIM: Irritable bowel syndrome (IBS) is a common disorder and many patients fail to find adequate relief from conventional therapies for their symptoms. This study tests the claim that acupuncture is effective for a majority of these patients.METNODS: A prospective, blinded, sham acupuncturecontrolled trial of traditional Chinese acupuncture was performed at a single postgraduate teaching hospital in Europe. Sixty patients with well-established IBS were recruited. The blinded comparator was sham acupuncture administered by the second of two acupuncturists who alone was aware of the randomization, and who otherwise followed the prescription of the first. The primary endpoint was a defined fall in the symptom score at 13 wk (by intention to treat). The prior expectation was a 30%placebo response, and a response rate of 70% from acupuncture, for which the study was adequately powered.RESULTS: Patients in treated and sham groups improved significantly during the study-mean improvement in scores being equal (minus 1.9) and significant for both (P<0.05;one-tailed t test). There was a small numeric but nonsignificant difference between the response rate in patients receiving acupuncture (40.7%) and sham treatment (31.2%). Several secondary end-points marginally favored active treatment, but an improved symptom score of any degree of magnitude occurred more often with sham therapy (65.6% vs 59.2%). For no criterion was statistical significance approached.CONCLUSION: Traditional Chinese acupuncture is relatively ineffective in IBS in the European hospital setting,and the magnitude of any effect appears insufficient to warrant investment in acupuncture services.Alastair Forbes Sue Jackson Clare Walter Shafi Quraishi Meron Jacyna Max Pitcher 2005World Journal of Gastroenterology2005,11,26:22
10组织工程化人工神经修复长段神经缺损实验的初步报告显示文摘目的 研究组织工程化人工神经修复大鼠 2 .5cm长坐骨神经缺损的效果。方法 90只 2个月月龄的Lewis 1W雌性大鼠 ,按手术先后顺序随机分成 3个神经移植组 ,每组 3 0只。A组 :用种植同源雪旺细胞并具有内部支架结构的胶原神经管桥接 ,即组织工程化人工神经组。B组 :用无雪旺细胞但具有内部支架结构的胶原神经管桥接 ,即对照组。C组 :自体神经移植组。术后 6个月 ,进行神经电生理监测 ,神经肌肉组织学观察 ;用S 10 0和神经微丝蛋白免疫组化染色后 ,行轴突计数等检测。结果 完成对 2 1只大鼠 (每组 7只 )的实验评估。从A组和C组的胫前肌中均能诱发出波幅明显的神经肌肉复合动作电位 (CMAP) ,再生轴突已通过移植段神经全长 ,远端肌肉轻度萎缩。B组中则没有或仅记录到波幅很低的CMAP ,移植神经远端结缔纤维组织增生 ,再生轴突罕见 ,所支配肌肉明显萎缩。结论 组织工程化人工神经可用来修复大鼠长段神经缺损。沈尊理 Berger Alfred Hierner Robert Lohmeyer Joern Allmeling Christina Walter F.Gerhard 2001中华手外科杂志2001,17,2:22
11Pharmacologic therapy for acute pancreatitis显示文摘While conservative management such as fluid,bowel rest,and antibiotics is the mainstay of current acute pancreatitis management,there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis.Extensive review of preclinical studies,which include assessment of therapies such as anti-secretory agents,protease inhibitors,anti-inflammatory agents,and anti-oxidants are discussed.Many of these studies have shown therapeutic benefit and improved survival in experimental models.Based on available preclinical studies,we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis.To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies.Despite these discouraging clinical studies,there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients.Better understanding of acute pancreatitis pathophysiology and lessons learnedfrom past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis.Swetha Kambhampati Walter Park Aida Habtezion 2014World Journal of Gastroenterology2014,20,45:22
12前环皮下内置外固定架联合后环骶髂螺钉治疗不稳定骨盆骨折显示文摘目的评估应用前环皮下内置外固定架(internal fixation,INFIX)联合后环骶髂螺钉治疗不稳定骨盆骨折的临床疗效。方法2016年8月-2017年9月,采用前环皮下INFIX联合后环骶髂螺钉治疗不稳定骨盆骨折19例。其中男14例,女5例;年龄17~69岁,平均40.6岁。致伤原因:交通事故伤11例,高处坠落伤5例,重物砸伤3例。骨折根据Tile分型,B1型2例,B2型6例,C型11例。前环损伤包括双侧耻骨坐骨支骨折12例,单侧耻骨坐骨支骨折5例,耻骨联合分离2例;后环损伤包括骶髂韧带损伤2例,单侧髂骨骨折3例,单侧骶骨骨折11例,单侧骶髂关节脱位2例,双侧骶骨骨折1例。受伤至手术时间2~11 d,平均6.1 d。记录术中出血量及手术时间,观察骨折愈合情况及术后并发症情况。采用Matta评分标准评价骨折复位情况,采用Majeed评分标准评估患者术后功能。结果患者手术时间为47~123 min,平均61.4 min;术中出血量为50~115 mL,平均61.1 mL。术后1例发生植钉处切口浅表感染,1例发生单侧股外侧皮神经激惹,经相应处理后治愈或症状消失。无泌尿系统、生殖系统及肠道等损伤。所有患者均获随访,随访时间12~25个月,平均18.1个月。术后骨折均愈合,愈合时间8~13周,平均9.5周;无骨折不愈合、延迟愈合,内固定物松动、断裂等情况发生。2例术前腰骶丛神经损伤患者中,1例功能完全恢复,1例残留轻度跛行症状。末次随访时采用Matta评分标准评价骨折复位情况,获优13例、良6例,优良率100%;采用Majeed评分标准评价功能,获优15例、良4例,优良率100%。结论应用前环皮下INFIX联合后环骶髂螺钉治疗不稳定骨盆骨折临床疗效满意,并发症较少,是一种微创治疗骨盆环损伤的有效方法。陈家磊 方跃 Walter MChirume 杨云 严新安 2020中国修复重建外科杂志2020,34,1:20
13儿科肠外营养指南(2016版)推荐意见节译显示文摘儿科肠外营养指南英文完整版共分为14篇,刊登在2018年Clinical Nutrition 。除方法篇外,每篇均给出推荐意见列表。在此,我们将方法篇有关证据级别、推荐等级、推荐形式的相关说明以及其余13篇的推荐建议整理成中文版,供国内儿科医护人员参考学习。欧洲儿科胃肠肝病与营养学会 欧洲临床营养与代谢学会 欧洲儿科研究学会 中华医学会肠外肠内营养学分会 Walter Mihatsch K.Joosten J.B.van'Goudoever Alexandre Lapillonne D.Mesotten F.Joehum M.Domellof J.Bronsky S.Kolacek I.Hojsak Susan Hill Arich Riskin Corina Hartman 颜伟慧(译) 吴江(译) 王莹(译) 蔡威(译) 2018中华儿科杂志2018,56,12:18
14试论当代西方锻炼行为阶段理论显示文摘段艳平 Walter Brehm Petra Wagner 2006中国运动医学杂志2006,25,4:18
15限制热量摄入6个月对超重者寿命指标、代谢调节及氧化应激的影响——随机对照试验AuthorAffiliations:PenningtonBiomedicalResearchCenter.LouisianaStateUniversity.BatonRouge;andGarvan.InstituteforMedicalResearch.Dadinghurst,AustraIia(DrHeilbronn).显示文摘背景:长期限制热量摄入可延长啮齿类动物的寿命。但是,尚未有研究观测长期限制人体热量是否会影响其寿命及氧化应激指标,降低代谢率。 目的:在超重但不肥胖(体重指数为25—30)的人群中研究限制热量6个月伴/不伴运动对其产生的影响。 设计、地点及参试者:于2002年3月至2004年8月在位于路易斯安娜州首府巴顿鲁治的研究中心对48名不好动的健康人进行随机对照研究。 干预:参试者在6个月内随机分为4个组:对照组(饮食可维持体重);限制热量组(限制基线所需能量的25%);限制热量+运动组(限制12.5%的热量+运动增加12.5%的能耗);极低热量饮食组(每日摄入890keal,直至体重减少15%,随后采用维持体重的饮食)。 主要观测指标:机体组成;硫酸脱氢表雄酮(dehydroepiandrostemne sulfate,DHEAS)、葡萄糖及胰岛素水平;蛋白羰基化合物;DNA损伤;24小时能耗;核心体温。 结果:6个月时各组体重变化的均值(标准误)为:对照组-1.0%(1.1%);限制热量组-10.4%(0.9%);限制热量+运动组-10.0%(0.8%);极低热量饮食组-13.9%(0.7%)。6个月时,各干预组空腹血糖水平较基线明显降低(P均〈0.01),而DHEAS和葡萄糖水平没有改变。限制热量组及限制热量+运动组核心体温有所下降(P均〈0.05)。对机体组成进行校正后发现,对照组24小时静息能耗无变化,但限制热量组(-135kcal/d[42kcal/d])、限制热量+运动组(-117kcal/d[52kcal/d])和极低热量饮食组(-125kcal/d[35kcal/d])24小时静息能耗有所下降(P均〈0.008)。上述“代谢调节”(超出预计值的-6%)与对照组相比存在显著差异(P〈0.05)。6个月时,各组蛋白羰基化合物的浓度较基线时无变化,而各干预组DNA损伤有所减少(P〈0.005)。 结论:我们的研究结果显示,长期限制热量可降低人类寿命的2种指标(即空腹胰岛素水平和体温)。此外,我们的研究结果还支持下述理论,即限制热量能降低代谢率,且超过缩小代谢面积产生的相应效应。我们尚需开展远期研究来评价限制热量能否延缓人类衰老过程。Leonie K. Heibronn Lilian de Jonge Madlyn I. Frisard James P. DeLany D. Enette Larson-Meyer Jennifer Rood Tuong Nguyen Corby K. Martin Julia Volaufova Marlene M. Most Frank L. Greenway Steven R. Smith Walter A. Deutsch Donald A. Williamson Eric Ravussin 顾佳(译) 2006美国医学会杂志(中文版)2006,25,5:18
16北极海洋沉积物中持久性有机污染物分布特征及分子地层学记录的研究显示文摘卢冰 陈荣华 王自磐 朱纯 WALTER Vetter 2005海洋学报2005,27,4:16
17基于嗅觉神经网络采用时间序列的电子鼻模式分类方法显示文摘从传感器阵列响应曲线中提取有效特征是传统人工神经网络在电子鼻模式识别应用中的第一步.文中提出将传感器阵列时间序列信号直接输入到一种具有丰富动力学特性的嗅觉神经网络中进行模式分类的方法.该方法不仅在仿生角度上使电子鼻进一步模拟了生物嗅觉系统信息处理过程,而且与以前所用的特征提取加神经网络的方法相比,在6种有机挥发物的分类识别中表现得更佳.傅均 李光 Walter J. Freeman 2007传感技术学报2007,20,9:16
18世界卫生组织-世界麻醉医师学会联盟(WHO-WFSA):麻醉安全国际标准显示文摘此麻醉安全国际标准由世界麻醉医师学会联盟(World Federation of Societies of Anaesthesiologists,WFSA)和世界卫生组织(World Health Organization,WHO)联合制订。WFSA是由150个国家的麻醉医师组成的非营利组织。本文所推荐的标准已获得WHO和WFSA成员支持,此标准适用于世界各地的麻醉工作者,旨在为麻醉工作者、专业组织、医院、机构管理者和政府提供指导和帮助,以维持和提高麻醉安全和质量。此标准涵盖专业内容、设施设备、用药及静脉输液、监测和麻醉实施等方面。高度推荐标准与强制标准作用等同,包括(但不仅限于):训练有素的、警惕的麻醉工作者持续在场,通过临床观察及脉搏血氧饱和度持续监测组织氧合及灌注;间断监测血压;通过听诊和二氧化碳检测确认气管内插管(如果有)的正确位置;应用WHO手术安全核查单;麻醉结束时完善交接系统。此国际标准仅为最低标准,而我们的目标是以所能达到的最高标准来实施麻醉,所以实际标准最好超过本文所介绍的标准。Adrian W.Gelb Wayne W.Morriss Walter Johnson Alan F.Merry. 2018中华麻醉学杂志2018,38,10:16
19同地共栖四种蝙蝠食性和回声定位信号的差异及其生态位分化显示文摘本研究于 2 0 0 2年 5月初至 2 0 0 3年 9月中旬在北京房山区霞云岭四合村蝙蝠洞进行 ,分析了共栖同一山洞四种蝙蝠的形态特征、食性和回声定位信号。大足鼠耳蝠食谱中以宽鳍等三种鱼为主 (体积百分比为5 3% ) ,回声定位主频 4 1 87± 1 0 7kHz;马铁菊头蝠主要掠捕鳞翅目昆虫 (73% ) ,恒频叫声主频 74 70± 0 13kHz ;中华鼠耳蝠以近地面或在地表活动的鞘翅目昆虫步甲类和埋葬甲类为主要食物 (6 5 4 % ) ,声脉冲主频较低 35 73± 0 92kHz;白腹管鼻蝠捕食花萤总科和瓢虫科等鞘翅目昆虫 (90 % ) ,回声定位信号主频为 5 9 4 7±1 5 0kHz。结果证实同地共栖四种蝙蝠种属特异的回声定位叫声和形态结构的差异 ,以及不同的捕食生境和捕食策略 。马杰 Walter METZNER 梁冰 张礼标 张劲硕 张树义 沈钧贤 2004动物学报2004,50,2:15
20Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations显示文摘AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD.METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing highperformance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP.RESULTS: NOD2/CARD15 mutations were found in 185patients (35.1%) and in 33 controls (16.5%, P<0.0001).SNP8/R702W (10.8% vs 6%, P = 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P = 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vscontrols: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet = 1.71,95%CI = 1.12-2.6, P= 0.0001, ORtwo-riskalleles = 25.2,95%CI = 4.37- , P<0.0001), early disease onset (carrier:26.4 years vs non-carrier: 29.8 years, P = 0.0006), ileal disease (81.9% vs 69.5%, OR = 1.99, 95%CI = 1.29-3.08,P = 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs64.8%), stricturing behavior (OR = 1.69, 95%CI = 1.13-2.55,P = 0.026) and increased need for resection (OR=1.71,95%CI: 1.13-2.62, P= 0.01), but not with duration, extraintestinal manifestations, familial disease or smoking. TLR4exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P= 0.06), in NOD2mut/wt: 26.7 years.CONCLUSION: These results confirm that variant NOD2/CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease,stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4mutation carriers tended to present at earlier age.Peter Laszlo Lakatos Laszlo Lakatos Ferenc Szalay Claudia Willheim-Polli Christoph (O|¨)sterreicher Zsolt Tulassay Tamas Molnar Walter Reinisch Janos Papp Gyula Mozsik Hungarian IBD Study Group Peter Ferenci 2005World Journal of Gastroenterology2005,11,10:14
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