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应用超敏感的基于NGS文库微滴的数字PCR方法检测非小细胞肺癌患者ctDNA的t790M突变

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应用超敏感的基于NGS文库微滴的数字PCR方法检测非小细胞肺癌患者...

Association of Chronic Kidney Disease with Non-alcoholic Fatty Liver Disease in Community Population with Increased Fasting Blood-glucose Level

2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛

作者：李俊杨科赵九州任鹏飞王志中魏冰董冰孙瑞王小艳 Groen,harry J.M 马杰郭永军河南省肿瘤医院

目的 EGFR t790M突变是非小细胞肺癌患接受一/二代EGFR-tKIs治疗后最主要的耐药标记。由于临床工作中组织二次活检率低,通过液体活检明确循环肿瘤DNA(ctDNA)中t790M的突变状态对于疾病监控和治疗决策至关重要。当前对ctDNA中t790M的检...

目的 EGFR t790M突变是非小细胞肺癌患接受一/二代EGFR-tKIs治疗后最主要的耐药标记。由于临床工作中组织二次活检率低,通过液体活检明确循环肿瘤DNA(ctDNA)中t790M的突变状态对于疾病监控和治疗决策至关重要。当前对ctDNA中t790M的检测方法主要包括ARMS-PCR、ddPCR以及二代测序(NGS);ddPCR和NGS敏感性较高,前者检测快(1.5天)通量低,后者通量高耗时长(1周)。但是由于ctDNA的产量较低,t790M在ctDNA中的检出率(约40%)远低于组织活检FFPE样本(约60%)。如何在提高ctDNA中t790M的检出率是当前需要解决的迫切问题。方法我们将NGS和ddPCR的方法进行整合,即以ctDNA为模板建立NGS预文库实现目标片段的扩增和富集,随后以预文库微滴为底物通过ddPCR检测t790M状态;对于LAB-ddPCR检测出的t790M阴性患者,进而通过二代测序全面判断其他变异位点的信息。结果我们的结果显示:1.以t790M变异比例(VFs)为0.1%的ctDNA标准品进行ddPCR检测,当上样量为300ng时所生成的有效微滴数最高且检出的t790M VFs没有发生偏移;2.无论是标准品还是23例患者来源的ctDNA样本,LAB-ddPCR表现出极高的检测灵敏度(0.05%)和特异性(100%),检出的t790M VFs与NGS高度一致(R2=0.9995);3.在70例对EGFR-tKIs耐药的NSCLC的ctDNA样本中,LAB-ddPCR共检出41例t790M阳性(58.57%),而传统的ddPCR仅检出27例(38.57%);其中27例两种检测均检测为阳性的样本,t790M的突变丰度高度一致(R2=0.9647);4.在21例NSCLC配对的二次活检和ctDNA样本中,LAB-ddPCR ctDNA t790M检测与二次组织活检t790M检测的一致率为80.95%,而传统ddPCR与二次活检结果的一致率仅有61.9%。结论 LAB-ddPCR克服了临床样本ctDNA产量低的缺点,极大地提高了ctDNA t790M检测的敏感性;该方法特异性高、可重复性好,与二次活检样本的结果高度一致,更真实地反映了t790M的突变状况,为靶向治疗提供快速、准确的信息。

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器官移植内科学杂志 2014年第2期9卷 54-59页

作者： Yongqiang Li Shuangshuang Zhu Xiaofei Shao Xinyu Liu Aiqun Liu Ying Zhang Honglei Wang Bin Li Kangping Deng Qin Liu harry Holthofer Hequn Zou Institute of Nephrology and Urology The Third Affiliated Hospital of Southern Medical University Guangzhou 510630 China. National Centre for Sensor Research/BioAnalytical Sciences Dublin City University Dublin 9 Ireland.

Objective Our current study aimed to study the relationship between NAFLD and CKD in population with Fasting blood-glucose Level >t 5.6mmol/1. Methods A cross-sectional study was conducted in Zhuhai city from June to October 2012. total 190 resodents were enrolled in this study. CKD was defined as eGFR 30mg/g. NAFLD was diagnosed on the basis of ultrasonographic and excluded fatty liver disease caused by other reasons such as *** association between NAFLD and CKD was then analyzed with SPSS (version 19.0). Results Subjects with NAFLD were more likely with a higher urinary albumin to creatinine ratio (Ptients with NAFLD than those without NAFLD (Ptly associated with CKD (Pthe unadjusted analyses as well as after adjustment for potential confounders. When adjusted for hypertension,high school or above, current smoking, physical inactivity, serum high density lipoprotein and serum fasting glucose, the association of NAFLD and CKD was significant (OR 2.67, 95% CI 1.07 to 6.69, P=0.036). Conclusions Our current study suggest that ultrasound-diagnosed NAFLD is associated with CKD among population with prediabetes or diabetes.

关键词：空腹血糖脂肪肝酒精性血糖水平慢性肾脏病合并超声诊断

Inflammation and reactive oxygen species in cardiovascular disease

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World Journal of Cardiology 2010年第12期2卷 408-410页

作者： Bradley t Andresen Department of Internal Medicine 1 Medical Pharmacology and Physiology and Harry S Truman VAMC

Reactive oxygen species(ROS)have long been proposed to be mediators of experimental cardiovascular *** is also a wealth of data indicating that ROS are involved in clinical cardiovascular ***,multiple clinical studies have shown little benefit from anti-oxidant treatments,whereas nearly all experimental studies have shown a marked effect of anti-oxidant *** reason for this discrepancy is that ROS are produced through multiple different mechanisms of which some are clinically beneficial;thus,in a defined experimental system where predominately pathological ROS are generated does not mimic a clinical setting where there are likely to be multiple ROS generating systems producing beneficial and pathological *** inhibition of ROS would not be expected to have the same result in these two situations;ergo,it is important to understand the molecular mechanism underlying the production of ROS so that clinical treatments can be tailored to target the pathological production of *** such example of this in cardiovascular biology is tissue specific inflammation-mediated ROS *** and the following series of articles discuss the current understanding of the role of ROS in cardiovascular disease,specifically focusing on the molecular mechanisms of ROS generation and the actions of ROS within the cardiovascular *** there are still many areas with regard to the effects of ROS in the cardiovascular system that are not completely understood,there is a wealth of data suggesting that blocking pathological ROS production is likely to have beneficial clinical effects compared to traditional anti-oxidants.

关键词： Anti-oxidants Inflammation Oxidants Pathology Reactive oxygen species

大型动物的种群恢复:大象种群增长的生态学效应

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AMBIO－人类环境杂志 2004年第6期33卷 254-260页

作者： Christina Skarpe Per Arild Aarrestad harry P.Andreassen Shivcharn S.Dhillion thatayaone Dimakatso Johan t.dutoit Duncan J.Halley Hkan Hytteborn Shimane Makhabu Moses Mari Wilson Marokane Gaseitsiwe Masunga Ditshoswane Modise(+) Stein R.Moe Rapelang Mojaphoko David Mosugelo Sekgowa Motsumi Gosiame Neo-Mahupeleng Mpho Ramotadima Lucas Rutina Lettie Sechele thato B.Sejoe Sigbjφrn Stokke Jon E.Swenson Cyril taolo Mark Vandewalle Per Wegge 周立志 Norwegian Institute for Nature Research Tungasletta 2N-7485 TrondheimNorway

博茨瓦纳北部及其毗邻地区分布着世界上最大的非洲象种群(Loxodonta africana),而在100年前,由于过度捕猎,大象的种群数量极为稀少。与此同时,有蹄类由于疾病,种群数量严重下降。大型草食性动物种群数量降低的生态学效应一定是显著的,... 详细信息

博茨瓦纳北部及其毗邻地区分布着世界上最大的非洲象种群(Loxodonta africana),而在100年前,由于过度捕猎,大象的种群数量极为稀少。与此同时,有蹄类由于疾病,种群数量严重下降。大型草食性动物种群数量降低的生态学效应一定是显著的,但我们却知之甚少,不过,目前博茨瓦纳大象种群数量上升之后产生的生态系统变化却引起人们相当大的关注。调查大象种群和其它生态系统组分及过程相互作用的项目"BONIC"就是的基于这种背景。调查结果表明,生态系统随着大象和其它有蹄类的种群数量的增长而发生变化,并且可能向着原先大型草食性动物数量减少之前的方向变化。我们认为人为地改变大象的种群数量没有生态学理由,但控制大象数量有经济和社会道理,而且博茨瓦纳北部大象的分布区可能必须要受到人为限制。

关键词：大象种群数量草食性动物生态系统有蹄类博茨瓦纳贝专纳种群恢复黑斑羚取食压力生态学效应种群增长

发生结直肠癌的实体器官移植患者的特征与生存方式

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世界核心医学期刊文摘（胃肠病学分册） 2005年第6期1卷 20-21页

作者： Papaconstantinou H.t. Sklow B. Hanaway M.J. 李康 Department of Surgery University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Mail L. 9156 Dallas TX 75390-9156 United States Dr.

PURPOSE: Immunosuppression used in transplantation is associated with an increased incidence of various cancers. Although the incidence of colorectal cancer in transplant patients seems to be equal to nontransplant population, the effects of immunosuppression on patients who develop colorectal cancer are not well defined. the purpose of this study was to define the characteristics and survival patterns of transplant patients developing de novo colorectal cancer. MEtHODS: the Israel Penn International transplant tumor Registry was queried for patients with colorectal cancer. Analysis included patient demographics, age at transplantation and colorectal cancer diagnosis, tumor stage, and survival. Age and survival rates were compared to United States population-based colorectal cancer statistics using the National Cancer Institute Surveillance Epidemiology and End Results database. RESULtS: A total of 150 transplant patients with de novo colorectal cancer were identified: 93 kidney, 29 heart, 27 liver, and 1 lung. Mean age at transplantation was 53 years. Age at transplantation and colorectal cancer diagnosis was not significant for gender, race, or stage of disease. Compared to National Cancer Institute Surveillance Epidemiology and End Results database, transplantation patients had a younger mean age at colorectal cancer diagnosis (58 vs. 70 years; P t, P t, P t, P t, P = 0.08). CONCLUSIONS: transplant patients develop colorectal cancer at a younger age and exhibit worse five-year survival rates than the general population. these data suggest that chronic immunosuppression results in a more aggressive tumor biology. Frequent posttransplantation colorectal cancer screening program may be warranted.

关键词：结直肠癌实体器官移植结肠直肠癌免疫抑制药物移植肿瘤肿瘤分期肿瘤生物学移植受者肺移植统计资料

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新一代物理实验中的微处理器

成都科技大学学报 1982年第1期 147-150页

作者：惲瑛王骏南京工学院成都科技大学

美国栾斯里尔多科性工业学院(RPI)物理系教授*** Resnick和*** ***,于1981年5月来华,在南京工学院讲学期问,从各个角度展示了当代工科物理教学的变化图景。也谈到一组极其微妙的概念群:从工科普通物理教学到火星登陆舱的研制;从基本技... 详细信息

美国栾斯里尔多科性工业学院(RPI)物理系教授*** Resnick和*** ***,于1981年5月来华,在南京工学院讲学期问,从各个角度展示了当代工科物理教学的变化图景。也谈到一组极其微妙的概念群:从工科普通物理教学到火星登陆舱的研制;从基本技能训练到按电钮方式的新一代物理实验,……这一切构成了现代工科物理教学结构。在工科物理教学方面,RPI每周仪有两小时课堂讲授,然后用按电钮方式(听录

关键词：物理实验新一代微处理器工科物理

Contribution of oxidative stress to pulmonary arterial hypertension

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World Journal of Cardiology 2010年第10期2卷 316-324页

作者： Vincent G DeMarco Adam t Whaley-Connell James R Sowers Javad Habibi Kevin C Dellsperger Department of Internal Medicine University of Missouri School of Medicine Diabetes and Cardiovascular Laboratory University of Missouri School of Medicine Department of Medical Pharmacology and Physiology University of Missouri School of Medicine harry S truman Veterans Affair Medical Center

Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of Et-1 (Et receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortali

关键词： Pulmonary arterial hypertension Rosuvastatin Oxidative stress Nicotinamide adenine dinucleotide phosphate oxidase Statins

2019年全球、地区和国家5岁以下儿童呼吸道合胞病毒引发急性下呼吸道感染疾病负担研究的系统分析

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中国病毒病杂志 2023年第2期13卷 81-95页

作者： You Li Xin Wang Dianna M.Blau Mauricio t.Caballero Daniel R.Feikin Christopher J.Gill Shabir A.Madhi Saad B.Omer Eric A.F Simoes harry Campbell Ana Bermejo Pariente Darmaa Bardach Quique Bassat Jean-Sebastien Casalegno Giorgi Chakhunashvili Nigel Crawford Daria Danilenko Lien Anh Ha Do Marcela Echavarria Angela Gentile Aubree Gordon terho Heikkinen QSue Huang Sophie Jullien Anand Krishnan Eduardo Luis Lopez Josko Markic Ainara Mira-Iglesias Hannah CMoore Jocelyn Moyes Lawrence Mwananyanda DJames Nokes Faseeha Noordeen Evangeline Obodai Nandhini Palani Candice Romero Vahid Salimi Ashish Satav Euri Seo Zakhar Shchomak Rosalyn Singleton Kirill Stolyarov Sonia K Stoszek Anne von Gottberg Danielle Wurzel Lay-Myint Yoshida Chee Fu Yung Heather J Zar Harish Nair 张甜甜从兵兵邓舒予不详南京医科大学公共卫生学院江苏南京211166

背景呼吸道合胞病毒(respiratory syncytial virus,RSV)是引起婴幼儿急性下呼吸道感染最常见的病原体。此前估计,2015年全球60月龄以下儿童共发生3 310万次RSV相关急性下呼吸道感染,导致118 200人死亡。此后,几项社区监测研究获得了对RS... 详细信息

背景呼吸道合胞病毒(respiratory syncytial virus,RSV)是引起婴幼儿急性下呼吸道感染最常见的病原体。此前估计,2015年全球60月龄以下儿童共发生3 310万次RSV相关急性下呼吸道感染,导致118 200人死亡。此后,几项社区监测研究获得了对RSV相关社区死亡的更精确估计。本文旨在更新2019年全球、地区和国家层面60月龄以下儿童RSV相关急性下呼吸道感染的发病率和死亡率,重点关注总体死亡率和在研RSV免疫制剂针对的更窄的婴儿年龄组。方法检索获得MEDLINE、Embase、Global Health、CINAHL、Web of Science、LILACS、OpenGrey、中国知网、万方和维普数据库2017—2020年发表文献中的新数据,并纳入RSV GEN合作者提供的未发表数据,以扩展全球RSV疾病负担数据集。纳入的研究符合以下条件:报告了社区中或需要住院治疗的60月龄以下儿童RSV原发性急性下呼吸道感染的数据;报告了至少连续12个月的数据,但院内病死率或RSV季节性定义明确的地区除外;报告了RSV相关急性下呼吸道感染的发病率、住院率、院内病死率或急性下呼吸道感染住院的RSV阳性比例。如果病例定义不明或应用不一致、RSV感染未经实验室确认或仅基于血清学检测、报告的急性下呼吸道感染病例少于50例,则排除该研究。本研究应用广义线性混合效应模型(generalized linear mixed-effects model,GLMM)估计了2019年全球和地区(按国家发展状况和世界银行收入分类)RSV相关急性下呼吸道感染的发病率、住院率和院内病死率;通过基于危险因素的模型估计了国家层面RSV相关急性下呼吸道感染的发病率;通过GLMM开发了新模型,纳入最新的RSV社区死亡率数据,用于估计RSV的总体死亡率。本综述已在PROSPERO注册(CRD42021252400)。结果除了先前综述中纳入的317项研究外,还纳入了113项符合条件的新研究以及51项未发表的研究,共计481项研究。据估计,2019年全球60月龄以下儿童中,共发生3 300万(置信区间为2 540万~4 460万)次RSV相关急性下呼吸道感染,导致360万(290万~460万)例住院、26 300(15 100~49 100)例院内死亡以及101 400(84 500~125 200)例可归因于RSV的总死亡数。在0~6个月的婴儿中,共发生660万(460万~970万)次RSV相关急性下呼吸道感染,导致140万(100万~200万)例住院、13 300(6 800~28 100)例院内死亡以及45 700(38 400~55 900)例可归因于RSV的总死亡数。60月龄以下和28 d~6月龄儿童的死亡中分别有2.0%(置信区间为1.6%~2.4%)和3.6%(3.0%~4.4%)归因于RSV。在各年龄组中,95%以上的RSV相关急性下呼吸道感染事件和97%以上的可归因于RSV的死亡事件都发生在中低收入国家。结论 RSV显著增加了全球60月龄以下儿童的发病和死亡负担,尤其是在出生后前6个月和中低收入国家。本研究强调了全球RSV疾病的总体死亡率负担,60月龄以下儿童中,每50例死亡就有1例可归因于RSV;28 d至6个月大的婴儿中,每28例死亡就有1例可归因于RSV。每1例RSV相关急性下呼吸道感染院内死亡,对应社区中约3例可归因于RSV的死亡。对6月龄内婴儿提供保护的RSV被动免疫计划有望对减轻RSV疾病负担,但实施计划时,仍需要更多数据来了解RSV疾病负担高峰可能向大龄转移的影响。

关键词：呼吸道合胞病毒下呼吸道感染儿童疾病负担住院发病率死亡率病死率模型估计系统分析

21世纪的卒中新定义：美国心脏协会／美国卒中协会对医疗专业人员的声明

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国际脑血管病杂志 2014年第1期22卷 5-27页

作者： Ralph L. Sacco Scott E. Kasner Joseph P. Broderick Louis R. Caplan J.J. (Buddy) Connors Antonio Culebras Mitchell S.V. Elkind Mary G. George Allen D. Hamdan Randall t. Higashida Brian L. Hoh L. Scott Janis Carlos S. Kase Dawn O. Kleindorfer Jin-Moo Lee Michael E. Moseley Eric D. Peterson tanya N. turan Amy L. Valderrama harry V. Vinters 王胜男(译) 吴齐恒(译) 邓镇(译) 周晓(译) 袁超(译) 潘速跃(译) 不详南方医科大学南方医院神经内科 510515

尽管脑血管病的影响广泛且对其病理生理学的理解已取得一些进展，但“卒中”一词在临床实践、临床研究和公共卫生评价中的定义并不统一。经典的卒中定义主要是临床定义，不能反映科学技术的进步。因此，美国心脏协会卒中委员会／美国卒... 详细信息

尽管脑血管病的影响广泛且对其病理生理学的理解已取得一些进展，但“卒中”一词在临床实践、临床研究和公共卫生评价中的定义并不统一。经典的卒中定义主要是临床定义，不能反映科学技术的进步。因此，美国心脏协会卒中委员会／美国卒中协会召集了一个写作组，旨在对21世纪的卒中新定义制定一份专家共识文件。中枢神经系统（centralnervoussystem，CNS）梗死被定义为缺血导致的脑、脊髓或视网膜细胞死亡，并且具有永久性损伤的神经病理学、神经影像学和（或）临床证据。CNS梗死具有一系列临床表现：缺血性卒中特指伴有明显症状的CNS梗死，而无症状梗死则顾名思义不引起明显症状。广义的卒中还包括脑出血和蛛网膜下腔出血。卒中的新定义结合了临床和组织学标准，因此能被融入临床实践、研究和公共卫生评价。

关键词：美国心脏协会科学声明脑出血脑梗死卒中蛛网膜下腔出血短暂性脑缺血发作