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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | 1990—2017年中国伤害负担:2017年全球疾病负担研究结果(摘译)显示文摘伤害是全球性的公共卫生挑战,涉及各年龄组和不同性别的人群。过去三十年来,中国经济快速发展,人口老龄化趋势加重,社会呈现出城镇化、机动化和老龄化等特征。随着人们生活环境和生活方式的改变,伤害已跃居人群致死原因第五位,仅排在恶性肿瘤、心脑血管疾病、呼吸系统疾病和心肌梗死之后。据估计,中国每年在伤害方面消耗的直接医疗费用约为650亿元人民币. | 林泽婷(译) 吕来文(译) 黄晓晴(译) 李丽萍(审校) Duan Leilei Ye Pengpeng Juanita A Haagsma Jin Ye Wang Yuan Er Yuliang Deng Xiao Gao Xin Ji Cuirong Wang Linhong Marlena S Bannick W Cli Mountjoy-Venning Caitlin N Hawley Zichen Liu Mari Smith Spencer L James Theo Vos Christopher J L Murray | 2020 | 伤害医学(电子版)2020，9，2： | 15 |
| 3 | 抗炎介质表达缺陷参与中性粒细胞型支气管哮喘发病机制:半乳糖凝集素-3和白细胞介素-1RA/白细胞介素-1beta比例显著下降显示文摘支气管哮喘(哮喘)是具有异质性的气道炎症性疾病,其主要特点表现为气道高反应和可变的气流受限。在哮喘的发病机制中,过敏原诱导的TH2淋巴细胞激活以及IL-5介导的嗜酸粒细胞渗出起到重要的作用。近年来发现超过50%的哮喘患者气道的嗜酸粒细胞水平并不增高,并将这种亚型定义为非嗜酸粒细胞型哮喘。其中部分患者表现为气道中性粒细胞明显增高,称为中性粒细胞型哮喘。 | 高鹏 Peter G Gibson Katherine J Baines Ian A Yang John W Upham Paul N Reynolds Sandra Hodge Alan L James Christine Jenkins Matthew J Peters 张捷 Jodie L Simpson | 2016 | 中华结核和呼吸杂志2016，39，11： | 5 |
| 4 | Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus显示文摘AIM:To assess tumour regression grade(TRG)and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS:Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005and 2011 at a single institution were reviewed.Triplet neoadjuvant chemotherapy consisting of platinum,fluoropyrimidine and anthracycline was considered for operable patients(World Health Organization performance status≤2)with clinical stage T2-4 N0-1.Response to neoadjuvant chemotherapy(NAC)was assessed using TRG,as described by Mandard et al.In addition lymph node downstaging was also assessed.Lymph node downstaging was defined by cN1 at diagnosis:assessed radiologically(computed tomography,positron emission tomography,endoscopic ultrasonography),then pathologically recorded as N0 after surgery;ypN0 if NAC given prior to surgery,or pN0if surgery alone.Patients were followed up for 5 years post surgery.Recurrence was defined radiologically,with or without pathological confirmation.An association was examined between t TRG and lymph node downstaging with disease free survival(DFS)and a comprehensive range of clinicopathological characteristics.RESULTS:Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years(median follow up:2.552,95%CI:2.022-3.081).There was a 1.8%(n=4)inpatient mortality rate.One hundred and thirty-six(62.4%)patients received NAC,with 74.3%(n=101)of patients demonstrating some signs of pathological tumour regression(TRG 1-4)and 5.9%(n=8)having a complete pathological response.Forty four point one percent(n=60)had downstaging of their nodal disease(cN1 to ypN0),compared to only 15.9%(n=13)that underwent surgery alone(pre-operatively overstaged:cN1 to pN0),(P<0.0001).Response to NAC was associated with significantly increased DFS(mean DFS;TRG 1-2:5.1years,95%CI:4.6-5.6 vs TRG 3-5:2.8 years,95%CI:2.2-3.3,P<0.0001).Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC(median DFS;TRG 3-5 and nodal down-staging:5.533 years,95%CI:3.558-7.531 vs TRG 3-5 and no nodal down-staging:1.114 years,95%CI:0.961-1.267,P<0.0001).CONCLUSION:Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. | Fergus Noble Luke Nolan Adrian C Bateman James P Byrne Jamie J Kelly Ian S Bailey Donna M Sharland Charlotte N Rees Timothy J Iveson Tim J Underwood Andrew R Bateman | 2013 | World Journal of Gastroenterology2013，19，48： | 4 |
| 5 | Identification of Differentially Expressed Genes Associated with Cotton Fiber Development in a Chromosomal Substitution Line(CS-B22sh)显示文摘One of the impediments in the genetic improvement of cotton fiber is the paucity of information about genes associated with fiber development.Availability of chromosome arm substitution line CS- | SOLIMAN Khairy M BOLTON James J SAHA Sukumar JENKINS Johnie N | 2008 | 棉花学报2008，20，S1： | 4 |
| 6 | Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1–2 trial显示文摘 | Xin Shelley Wang Laurence D Rhines Almon S Shiu James N Yang Ugur Selek Ibrahima Gning Ping Liu Pamela K Allen Syed S Azeem Paul D Brown Hadley J Sharp David C Weksberg Charles S Cleeland Eric L Chang | 2012 | Lancet Oncology2012，，4： | 2 |
| 7 | A comparison of the relative efficiency of ICSI and extended culture with epididymal sperm versus testicular sperm in patients with obstructive azoospermia显示文摘This is a retrospective cohort study comparing blastocyst transfer outcomes following intracytoplasmic sperm injection utilizing epididymal versus testicular sperm for men with obstructive azoospermia.All cases at a single center between 2012 and 2016 were included.Operative approach was selected at the surgeon’s discretion and included microepididymal sperm aspiration or testicular sperm extraction.Blastocyst culture was exclusively utilized prior to transfer.The primary outcome was live birth rate.Secondary outcomes included fertilization rate,blastulation rate,euploidy rate,and implantation rate.A mixed effects model was performed.Seventy-six microepididymal sperm aspiration cases and 93 testicular sperm extraction cases were analyzed.The live birth rate was equivalent(48.6%vs 50.5%,P=0.77).However,on mixed effects model,epididymal sperm resulted in a greater likelihood of fertilization(adjusted OR:1.37,95%CI:1.05–1.81,P=0.02)and produced a higher blastulation rate(adjusted OR:1.41,95%CI:1.1–1.85,P=0.01).As a result,the epididymal sperm group had more supernumerary blastocysts available(4.3 vs 3,P<0.05).The euploidy rate was no different.Pregnancy rates were no different through the first transfer cycle.However,intracytoplasmic sperm injection following microepididymal sperm aspiration resulted in a greater number of usable blastocysts per patient.Thus,the true benefit of epididymal sperm may only be demonstrated via a comparison of cumulative pregnancy rates after multiple transfers from one cohort. | Scott J Morin Brent M Hanson Caroline R Juneau Shelby A Neal Jessica N Landis Richard T Scott Jr James M Hotaling | 2020 | Asian Journal of Andrology2020，22，2： | 2 |
| 8 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 9 | Gold nanoparticle imaging and radiotherapy of brain tumors in mice显示文摘 | James F Hainfeld Henry M Smilowitz Michael J O&rsquor Connor Farrokh Avraham Dilmanian Daniel N Slatkin | 2013 | Nanomedicine2013，，10： | 1 |
| 10 | Chemistry of toxic range plants highly oxygenated flavonoids methyl ethers from Gutierreziamicricephala 显示文摘 | JAMES N R LYNN F J | 1985 | Phytochemistry1985，24，4： | 1 |
| 11 | Endo- thelial cells derived from human iPSCS increase capillary density and improve peffusion in a mouse model of periph- eral arterial disease显示文摘 | RUFAIHAH A J HUANG N F JAME S | 2011 | Arterioscler Thromb Vasc Biol2011，31，： | 1 |
| 12 | Natural organic matter enhanced mobility of llano zerovalent iron 显示文摘 | Richard L J Graham O J James T N | 2009 | Environmental Science & Technology2009，43，14： | 1 |
| 13 | Catalysis at the metal-support interface exemplified by the photocatalytic reforming of methanol on Pd/TiO2显示文摘 | BOWKER M JAMES D STONE P BENNETT R PERKINS N MILLARD L GREAVES J DICKINSON A | 2003 | J Catal2003，217，2： | 1 |
| 14 | Effects of cellulose derivatives and carrageenans on the pasting, paste, and gel properties of rice starches 显示文摘 | Techawipharat J Suphantharika M James N B | 2008 | Carbohydrate Polymers2008，73，3： | 1 |
| 15 | Retrieval-induced forgetting in Alzheimer' s disease 显示文摘 | MOUL1N J A C PERFECT T J CONWAY M A JONES R W JAMES N | 2002 | Neuropsy- chologia2002，40，： | 1 |
| 16 | The structure of large and small airways in nonfatal and fatal asthma显示文摘 | Carroll N Elliot J Morton A James A | | 0，，： | 1 |
| 17 | Thrombolites and stromatolites : Two distincttypes of microbial structures 显示文摘 | Kennard J M James N P | 1986 | Palaios1986，1，5： | 1 |
| 18 | Photochemical treatment of platelet concentrates with amotosalen hydrochloride and ultraviolet A light inactivates free and latent cytomegalovirus in a murine transfusion model 显示文摘 | CETHERINE T J NATIA S JAMES N | 2004 | Transfusion2004，44，8： | 1 |
| 19 | Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction 显示文摘 | JAMES L JANUZZI JR MD SHAFIQ U REHMAN M D ASIM A MOHAMMED M D ANJU BHARDWAJ M D LINDA BARAJAS R N JUSTINE BARAJAS HAN-NA KIM M D MPH AARON L BAGGISH M D RORY B WEINER M D ANNABEL CHEN-TOURNOUX MD JANE E MARSHALL RDCS STEPHANIE A MOORE M D WILLIAM D CARLSON M D GREGORY D LEWIS M D JORDAN SHIN M D DOROTHY SULLIVAN ANP KIMBERLY PARKS D O THOMAS J WANG M D SHAWN A GREGORY M D SHANMUGAM UTHAMALINGAM M D MARC J SEMIGRAN M D | 2011 | J Am Coll Cardiol2011，58，18： | 1 |
| 20 | Rhinorrhea,cough and fatigue in patients taking Sitagliptin显示文摘 | James N Baraniuk Mary J Jamieson | | 0，，： | 1 |
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