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瑞舒伐他汀对存在亚临床动脉粥样硬化的低危人群颈动脉内膜中层厚度进展的影响——METEOR试验

美国医学会杂志（中文版） 2007年第4期26卷 208-216页

作者： John R. Crouse Ⅲ Joel S. Raichlen w.rd A. Riley gregory w. evans Mike K. Palmer Daniel H. O＇ Leary Diederick E. Grobbee Michiel L. Bots 李军（译） w.ke Forest University School of Medicine Medical Cel. ter Blvd Winston-SaJem NC 27157 Departments of Neurology Wake Forest University Winston- Salem NC Departments of Public Health Sciences Wake Forest University Winston- Salem NC AstraZeneca Wilmington Del AstraZeneca Macclesfield England Caritas Carney Hospital Boston Mass Department of Epidemiology Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht the Netherlands 不详

背景：动脉粥样硬化往往在机体出现症状之前就已有所进展。目前，我们尚不清楚Framingham风险评分（Framinghaln risk score，FRS）较低的轻中度亚临床动脉粥样硬化中年人群是否能从治疗中获益。目的：评价为期2年的他汀类药物治疗能否... 详细信息

背景：动脉粥样硬化往往在机体出现症状之前就已有所进展。目前，我们尚不清楚Framingham风险评分（Framinghaln risk score，FRS）较低的轻中度亚临床动脉粥样硬化中年人群是否能从治疗中获益。目的：评价为期2年的他汀类药物治疗能否减缓颈动脉内膜中层厚度（carotid intimamedia thickness，CIMT）继续增厚或使粥样斑块消退。设计、地点及参试者：“瑞舒伐他汀对内膜中层厚度影响的测评研究（Measuring Effects on Intima-Media Thickness：an Evaluation of Rosuvastatin，METEOR）”是2002年8月至2006年5月在美国及欧洲61个基层医疗中心开展的一项随机、双盲、安慰剂对照研究，共纳入984名参试者，有的参试者仅以年龄（平均年龄，57岁）为冠心病的危险因素，有的参试者10年内FRS低于10％、CIMT重庞增厚（1．2～3．5mm）、LDL胆固醇水平有所升高（平均值，154mg／dL）。干预：参试者服用40mg瑞舒伐他汀或安慰剂。主要观测指标：12个颈动脉位点最大CIMT的变化率（经B超检测）；颈总动脉位点、颈动脉窦位点及颈内动脉位点最大CIMT的变化，颈总动脉位点平均CIMT的变化。仅在瑞舒伐他汀组中评估CIMT的消退情况。结果：瑞舒伐他汀组参试者LDL胆固醇平均（SD）水平由基线时的155（24．1）mg／dL降至78（27．5）mg／dL，平均降低49％（与安慰剂组相比P〈0.001）。瑞舒伐他汀组12个颈动脉位点最大CIMT的变化值为-0．0014（95％CI，-0．0041～0.0014）mm／y，安慰剂组12个颈动脉位点最大CIMT的变化值为Q0131（95％CI，Q0087～Q0174）mm／y（P〈0.001）。瑞舒伐他汀组颈总动脉位点最大CIMT的变化值为-0.0038（95％CI，-0.0064～-0.0013）mm／y（P〈0.001），颈动脉窦位点最大CIMT的变化值为-0.0040（95％CI，-0.0090～0.0010）mm／y（P〈0.001），颈内动脉位点最大CIMT的变化值为0.0039（95％CI，-0.0009～0.0088）mm／y（P=0.02）。瑞舒伐他汀组颈总动脉位点平均CIMT的变化值为0.0004（95％CI，-0.0011～0.0019）mm／y（P〈0.001）。P值均为与安慰剂组相比。总的来说，瑞舒伐他汀具有良好的耐受性，很少引发严重的心血管不良事件（在2年内有6名参试者[0.86％]出现8起不良事件[1．1％]）。结论：对于FRS低于10％的亚临床动脉粥样硬化中年人群而言，瑞舒伐他汀能够在2年内显著降低最大CIMT的进展速率，与安慰剂相比差异具有统计学显著性。但是，瑞舒伐他汀无法诱导病变消退。今后，我们仍需开展大型远期试验来明确上述研究结果的临床意义．

关键词：亚临床动脉粥样硬化颈动脉内膜中层厚度瑞舒伐他汀低危人群 Rosuvastatin 试验心血管不良事件安慰剂对照

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RNA-based therapies in animal models of Leber congenital amaurosis causing blindness

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Precision Clinical Medicine 2020年第2期3卷 113-126页

作者： Xia w.ng Xianghong Shan Kevin gregory-evans Cheryl Y.gregory-evans Department of Ophthalmology and Visual Sciences University of British ColumbiaVancouver BC V5Z 3N9Canada

Leber congenital amaurosis(LCA)is a severe,genetically heterogeneous recessive eye disease in w.ich∼35%of genemutations are in-frame nonsensemutations coding for loss-of-function premature termination codons(PTCs)*** suppression therapy allow. read-through of PTCs leading to production of full-length protein.A limitation of nonsense suppression is that nonsense-mediated decay(NMD)degrades PTC-containing RNA *** purpose of this study w.s to determine w.ether inhibition of NMD could improve nonsense suppression efficacy in *** a high-throughput approach in the recessive cep290 zebrafish model of LCA(cep290;Q1223X),w. first tested the NMD inhibitor Amlexanox in combination w.th the nonsense suppression drug *** observed reduced retinal cell death and improved visual *** these positive data,w. next investigated w.ether this strategy w.s also applicable across species in tw. mammalianmodels:Rd12(rpe65;R44X)and Rd3(rd3;R107X)mouse models of *** the Rd12 model,cell death w.s reduced,RPE65 protein w.s produced,and in vivo visual function testing w.s *** establish for the first time that the mechanism of action of Amlexanox in Rd12 retina w.s through reduced UPF1 *** the Rd3 model,how.ver,no beneficial effect w.s observed w.th Ataluren alone or in combination w.th *** variation in response establishes that some forms of nonsensemutation LCA can be targeted by RNA therapies,but that this needs to be verified for each *** implementation of precision medicine by identifying better responders to specific drugs is essential for development of validated retinal therapies.

关键词： precision medicine Ataluren Amlexanox nonsense suppression RPE65 CEP290 RD3

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Animal models of amyotrophic lateral sclerosis： a comparison of model validity

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Neural Regeneration Research 2018年第12期13卷 2050-2054页

作者： Jessica R.Morrice Cheryl Y.gregory-evans Christopher A.Shaw Experimental Medicine Program University of British Columbia Vancouver Canada Department of Ophthalmology and Visual Sciences University of British Columbia Vancouver Canada Neuroscience Program University of British Columbia Vancouver Canada Department of Pathology. University of British Columbia Vancouver Canada

Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis（ALS）. Measures of model validity allow.for a critical interpretation of results from each model and caution from over-interpretation of experimental models. Face and construct validity refer to the similarity in phenotype and the proposed causal factor to the human disease, respectively. More recently developed models are restricted by limited phenotype characterization, yet new.models hold promise for novel disease insights, thus highlighting their importance. In this article, w. evaluate the features of face and construct validity of our new.zebrafish model of environmentally-induced motor neuron degeneration and discuss this in the context of current environmental and genetic ALS models, including C9 orf72, mutant Cu/Zn superoxide dismutase 1 and TAR DNA-binding protein 43 mouse and zebrafish models. In this mini-review. w. discuss the pros and cons to validity criteria in each model. Our zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity w.th many hallmarks of ALS-like features, and w.akness in construct validity. How.ver, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases, w.ere environmental factors may be more likely to be involved in disease etiology than single dominant gene mutations. It may be necessary to compare findings betw.en different strains and species modeling specific genes or environmental factors to confirm findings from ALS animal models and tease out arbitrary strain-and overexpression-specific effects.

关键词： amyotrophic lateral sclerosis motor neuron degeneration face validity construct validity zebrafish models mouse models genetic models environmental models

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Impact of delay from transperineal biopsy to radical prostatectomy upon objective measures of cancer control

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Asian Journal of Urology 2022年第2期9卷 170-176页

作者： Liang G.Qu gregory Jack Marlon Perera Melanie evans Sue evans Damien Bolton Nathan Papa Department of Urology Olivia Newton John Cancer CentreAustin HealthHeidelberg VICAustralia Department of Surgery University of MelbourneMelbourne VICAustralia Department of Epidemiology and Preventive Medicine Monash UniversityMelbourne VICAustralia

Objective:Treatment delays in prostate cancer have been characterised,although not explicitly in men undergoing transperineal prostate *** aimed to determine if delays to radical prostatectomy correlate w.th adverse outcomes using a contemporary population-based cohort of men diagnosed by transperineal ***:This study analysed men w.th prostate cancer of the International Society for Urological Pathology grade group≥2,diagnosed by transperineal prostate biopsies w.o underw.nt prostatectomy,using the prospectively data from 1 January 2014 to 30 June 2018 Prostate Cancer Outcomes *** w.re analysed according to stratified demographic and disease *** intervals from biopsy(28,60,90,120,and 270 days)w.re compared using odds ratios and regression analyses for proportion of upgrading,early biochemical recurrence,pT3 disease at prostatectomy,and positive surgical ***:In total,2008 men w.re *** w.re 306(16.7%)men w.th upgrading,151(8.4%)w.th biochemical recurrence,1068(54.1%)w.th pT3 disease,and 464(23.1%)w.th positive surgical margins(percentages excluded patients w.th missing data).All adverse outcomes studied w.re significantly associated w.th higher prostate-specific antigen and grade at *** of 120-270 days did not adversely alter the incidence of Gleason upgrading,pT3,or ***(most frequent 60-89 days,28%)w.re associated w.th positive surgical margins but not *** modelling demonstrated no increased likelihood of most adverse outcomes for up to 270 ***:Men w.th prostate cancer of grade group≥2 diagnosed through transperineal biopsy may w.it up to 270 days for a prostatectomy w.thout a greater likelihood of upgrading,pT3 disease,positive surgical margins,or biochemical recurrence.

关键词： Biopsy Disease progression Prostate cancer Recurrence Treatment delay

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Carotid Intima-media Thickness Measurements： Relations w.th Atherosclerosis, Risk of Cardiovascular Disease and Application in Randomized Controlled Trials

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Chinese Medical Journal 2016年第2期129卷 215-226页

作者： Michiel L Bots gregory w.evans Charles H Tegeler Rudy Meijer Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands Department of Biostatistical Sciences and Neurology Wake Forest School of Medicine Winston-Salem NC USA Department of Neuiology Ward A Riley Ultrasound Center Wake Forest School of Medicine Medical Center Boulevard Winston-Salem NC USA

Cardiovascular disease （CVD） is the leading cause of death w.rldw.de and contributes considerably to morbidity The underlying cause is atherosclerosisThe development of new.preventive therapies is one of the steps to control the CVD epidemic. It is increasingly demanded that promising therapies be evaluated in trials using cardiovascular （CV） morbidity and mortality （M and M） as a primary outcome.

关键词： Atherosclerosis Cardiovascular Disease Prevention Trials

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Stem cells and tissue engineering in plastic surgery:an update

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Plastic and Aesthetic Research 2020年第5期7卷 63-72页

作者： gregory R.D.evans Alan D.w.dgerow Department of Plastic Surgery University of CaliforniaIrvineOrangeCA 92868USA

Stem cells and tissue engineering have made great strides in plastic *** review.of the literature evaluates some current background information and recent advances in our laboratory to bring these areas more into the ... 详细信息

关键词： Stem cells plastic surgery fat

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Preparedness Paralysis:Ramifications for Pandemic Planning

Preparedness Paralysis:Ramifications for Pandemic Planning

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北京论坛（2006）文明的和谐与共同繁荣—对人类文明方式的思考

作者： R.gregory evans Rachel D.Schw.rtz Institute for Biosecurity Saint Louis University School of Public Health 3545 Lafayette Av.St.Louis MO 63104 USA

Recent disasters like terrorist attacks,tsunamis and hurricanes,and emerging infections have led to significant developments in the field of disaster preparedness and response as scientists, public health and healthcare personnel and governments realize that adequate preparedness is the only w.y to meet these *** only have the United States government and other countries placed a high priority on preparedness and response,but also many public and private companies and organizations have designated preparedness specialists to develop effective plans for *** the case of avian flu(H5N1),States,counties,private businesses and public organizations have been w.rking to develop their ow. response plans in the event that H5N1 becomes easily transmissible from human to human,and turns *** these organizations w.rk on their plans,they naturally turn to their governments for guidance and information on how.to ***,they are finding that many of their important questions go unansw.red,or that the answ.rs are changing and sometimes inconsistent or contradictory,even among experts in the ***,in the United States,the government’s ow. Pandemic Response plan is open to interpretation and,at time,a source of confusion.

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Hand and Upper Extremity Reconstruction

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2009年

作者： Kevin C. Chung Series Editor gregory R.D.evans

Includes bibliographical references and index.

ISBN: (纸本)9780702029165

Includes bibliographical references and index.

关键词： w.unds and Injuries

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Aesthetic and reconstructive surgery of the breast

Aesthetic and reconstructive surgery of the breast

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2010年

作者： Elizabeth J Hall-Findlay gregory R. D evans

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Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability

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Neural Regeneration Research 2017年第12期12卷 2045-2049页

作者： Allison H.Payne gregory w.Haw.yluk Yoshimi Anzai Henrik Odéen Megan A.Ostlie Ethan C.Reichert Amanda J.Stump Satoshi Minoshima Donna J.Cross Department of Radiology and Imaging Sciences University of Utah Salt Lake City UT USA Department of Neurosurgery University of Utah Salt Lake City UT USA

Spinal cord injury（SCI） affects thousands of people every year in the USA, and most patients are left w.th some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, w. used magnetic resonance imaging-guided focused ultrasound（MRg FUS） as a non-invasive approach to increase permeability in the blood-spinal cord barrier（BSCB）. w. hypothesize that localized, controlled sonoporation of the BSCB by MRg FUS w.ll aid delivery of therapeutics to the injury. Here, w. report our preliminary findings for the ability of MRg FUS to increase BSCB permeability in the thoracic spinal cord of a normal rat model. First, an excised portion of normal rat spinal column w.s used to characterize the acoustic field and to estimate the insertion losses that could be expected in an MRg FUS blood spinal cord barrier opening. Then, in normal rats, MRg FUS w.s applied in combination w.th intravenously administered microbubbles to the spinal cord region. Permeability of the BSCB w.s indicated as signal enhancement by contrast administered prior to T1-w.ighted magnetic resonance imaging and verified by evans blue dye. Neurological testing using the Basso, Beattie, and Breshnahan scale and the ladder w.lk w.s normal in 8 of 10 rats tested. Tw. rats show.d minor impairment indicating need for further refinement of parameters. No gross tissue damage w.s evident by histology. In this study, w. have opened successfully the blood spinal cord barrier in the thoracic region of the normal rat spine using magnetic resonance-guided focused ultrasound combined w.th microbubbles.

关键词： focused ultrasound spinal cord magnetic resonance imaging contrast-enhanced blood-spinalcord barrier

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