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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 | An epigenomic approach to therapy for tamoxifen-resistant breast cancer显示文摘Tamoxifen 是为雌激素受体 alpha 的前线治疗(ERα) 在绝经前的女人的积极的胸肿瘤。然而,到 tamoxifen 的抵抗发生在许多病人。嗯仍然与获得的 tamoxifen 抵抗在乳癌房间的生长起一个关键作用,建议那 ERα为治疗仍然是一个有效目标 tamoxifen 抵抗(Tam-R ) 乳癌。以识别 ERα 的新奇管理者;发信号,通过对 histone 甲基修饰词的一幅小规模的 siRNA 屏幕,我们发现了 WHSC1, histone H3K36 methyltransferase, ERα 的一个积极管理者;在乳癌房间发信号。我们证明 WHSC1 被招募到 ERα由 BET 蛋白质 BRD3/4 的基因,并且便于 ERα基因表示。小分子的赌注蛋白质禁止者 JQ1 potently 压制了经典 ERα发信号的小径和在文化的 Tam-R 乳癌房间的生长。用一个 Tam-R 乳癌异种皮移植老鼠模型,我们与 JQ1 和 ER degrader fulvestrant 由 JQ1 和联合治疗的强壮的长持续的效果在 vivo 反胸癌症活动示威了。一起拿,我们提供 epigenomic 蛋白质 BRD3/4 和 WHSC1 是雌激素受体发信号的必要管理者并且是为 Tam-R 乳癌的治疗的新奇治疗学的目标的证据。 | Qin Feng Zheng Zhang Martin J Shea Chad J Creighton Cristian Coarfa Susan G Hilsenbeck Rainer Lanz Bin He Lei Wang Xiaoyong Fu Agostina Nardone Yongcheng Song James Bradner Nicholas Mitsiades Constantine S Mitsiades C Kent Osborne Rachel Schiff Bert W O'Malley | 2014 | Cell Research2014，24，7： | 10 |
| 3 | Football injuries of the ankle: A review of injury mechanisms, diagnosis and management显示文摘Football is the most popular sport worldwide and is associated with a high injury rate, most of which are the result of trauma from player contact. Ankle injuries are among the most commonly diagnosed injuries in the game. The result is reduced physical activity and endurance levels, lost game time, and considerable medical cost. Sports medicine professionals must employ the correct diagnostic tools and effective treatments and rehabilitation protocols to minimize the impact of these injuries on the player. This review examines the diagnosis, treatment, and postoperative rehabilitation for common football injuries of the ankle based on the clinical evidence provided in the current literature. | Raymond J Walls Keir A Ross Ethan J Fraser Christopher W Hodgkins Niall A Smyth Christopher J Egan James Calder John G Kennedy | 2016 | World Journal of Orthopedics2016，7，1： | 5 |
| 4 | 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 |
| 5 | Gastric intestinal metaplasia is associated with gastric dysplasia but is inversely correlated with esophageal dysplasia显示文摘AIM To determine which clinical factors might be associated with gastric intestinal metaplasia(IM) in a North American population.METHODS Pathology and endoscopy databases at an academicmedical center were reviewed to identify patients with and without gastric IM on biopsies for a retrospective cohort study. Patient demographics, insurance status, and other clinical factors were reviewed.RESULTS Four hundred and sixty-eight patients with gastric IM(mean age: 61.0 years ± 14.4 years, 55.5% female) and 171 without gastric IM(mean age: 48.8 years ± 20.8 years, 55.0% female) were compared. The endoscopic appearance of atrophic gastritis correlated with finding gastric IM on histopathology(OR = 2.05, P = 0.051). Gastric IM was associated with histologic findings of chronic gastritis(OR = 2.56, P < 0.001), gastric ulcer(OR = 6.97, P = 0.015), gastric dysplasia(OR = 6.11, P = 0.038), and gastric cancer(OR = 6.53, P = 0.027). Histologic findings of Barrett's esophagus(OR = 0.28, P = 0.003) and esophageal dysplasia(OR = 0.11, P = 0.014) were inversely associated with gastric IM. Tobacco use(OR = 1.73, P = 0.005) was associated with gastric IM.CONCLUSION Patients who smoke or have the endoscopic finding of atrophic gastritis are more likely to have gastric IM and should have screening gastric biopsies during esophagogastroduodenoscopy(EGD). Patients with gastric IM are at increased risk for having gastric dysplasia and cancer, and surveillance EGD with gastric biopsies in these patients might be reasonable. | Justin M Gomez James T Patrie Wissam Bleibel Jeanetta W Frye Bryan G Sauer Vanessa M Shami Edward B Stelow Christopher A Moskaluk Andrew Y Wang | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，2： | 3 |
| 6 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials显示文摘 | Naveed Sattar David Preiss Heather M Murray Paul Welsh Brendan M Buckley Anton JM de Craen Sreenivasa Rao Kondapally Seshasai John J McMurray Dilys J Freeman J Wouter Jukema Peter W Macfarlane Chris J Packard David J Stott Rudi G Westendorp James Shepherd | 2010 | The Lancet2010，，9716： | 2 |
| 7 | Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression显示文摘 | Jason M Hui Archana Sud Geoffrey C Farrell Priyanka Bandara Karen Byth James G Kench Geoffrey W McCaughan Jacob George | 2003 | Gastroenterology2003，，6： | 2 |
| 8 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials显示文摘 | Naveed Sattar David Preiss Heather M Murray Paul Welsh Brendan M Buckley Anton JM de Craen Sreenivasa Rao Kondapally Seshasai John J McMurray Dilys J Freeman J Wouter Jukema Peter W Macfarlane Chris J Packard David J Stott Rudi G Westendorp James Shepherd | 2010 | The Lancet2010，，9716： | 2 |
| 9 | A multivariate analysis of work - life balance outcomes from a large -scale telework programme显示文摘 | TAKAO MARUYAMA PETER G HOPKINSON PETER W JAMES | 2009 | New Technology Work and Employment2009，24，1： | 1 |
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| 14 | Genome, transcriptome, and secretome analysis of wood decay fungus Postia placenta supports unique mechanisms of lignocellulose conversion 显示文摘 | Martinez D Challacombe J Morgenstern 1 Hibbett D Schmoll M Kubicek CP Ferreira P Ruiz-Duenas FJ Martinez AT Kersten P Hammel KE Wymelenberg AV Gaskell J Lindquist E Sabat G BonDurant SS Larrondo LF Canessa P Vicuna R Yadav J Doddapaneni H Subramanian V Pisabarro AG Lavin JL Oguiza JA Master E Henrissat B Coutinho PM Harris P Magnuson JK Baker SE Bruno K Kenealy W Hoegger PJ Kties U Ramaiya P kucas S Salamov A Shapiro H Tu H Chee CL Misra M Xie G Teter S Yaver D James T Mokrejs M Pospisek M Grigoriev IV Brettin T Rokhsar D Berka R Cullen D | 2009 | PNAS2009，106，6： | 1 |
| 15 | Five-dimensional optical re-cording mediated by surface plasmons in gold nanorods显示文摘 | PETER Z JAMES W M C MIN G | 2009 | Na-ture2009，459，7245： | 1 |
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