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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 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 3 | DEVELOPMENT AND MOTION ANALYSIS OF MINIATURE WHEEL-TRACK-LEGGED MOBILE ROBOT显示文摘A miniature wheel-track-legged mobile robot to carry out military and civilian missions in both indoor and outdoor environments is presented. Firstly, the mechanical design is discussed, which consists of four wheeled and four independently controlled tracked arms, embedded control system and teleoperation. Then the locomotion modes of the mobile robot and motion analysis are analyzed. The mobile robot can move using wheeled, tracked and legged modes, and it has the characteristics of posture-recovering, high mobility, small size and light weight. Finally, the effectiveness of the deve-loped mobile robot is confirmed by experiments such as posture recovering when tipped over, climb-ing stairs and traversing the high step. | DUAN Xingguang HUANG Qiang XU Yan RAHMAN N ZHENG Change | 2007 | Chinese Journal of Mechanical Engineering2007，20，3： | 11 |
| 4 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 5 | Development of Soybean EST-SSR Markers and Their Use to Assess Genetic Diversity in the Subgenus Soja显示文摘Developing expressed sequence tag-derived SSR(EST-SSR)markers is imperative in genetic research.In this paper,we reported 37 EST-SSR markers which were developed from 286 unigenes obtained from soybean cDNA library.Among the 286 markers designed for the 4 accessions of Glycine max and 6 of its wild progenitor(G.soja)within the subgenus Soja,209 markers amplified DNA fragments,taking 73.1% and 37 markers appeared to be polymorphic,which was 12.9% of the total.The 37 loci detected a total of 142 alleles,while the PIC values varied from 0.194 to 0.794.Both the number of alleles per locus and PIC value were significantly related to the SSR motif.Six EST-SSR loci may be fixed for different alleles between G.max and G.soja since they were particularly polymorphic among the 6 G.soja accessions.A neighbor-joining tree placed the G.max accessions together as a group within the G.soja,though the average genetic distance among G.soja accessions was much higher.These new EST-SSRs markers will be useful for genetic diversity analysis,genetic mapping construction and gene discovery in Soja subgenus. | LIU Yu-lin LI Ying-hui ZHOU Guo-an Uzokwe N CHANG Ru-zhen CHEN Shou-yi QIU Li-juan | 2010 | Agricultural Sciences in China2010，9，10： | 6 |
| 6 | Geographic Spread of Currency Trading:The Renminbi and Other Emerging Market Currencies显示文摘This paper studies the ongoing diffusion of renminbi (RMB) trading across the globe, the first of such research of an international currency. It analyses the distribution in offshore RMB trading in 2013 and 2016 using comprehensive data from the Triennial Central Bank Survey of foreign exchange markets. In 2013, Asian centers favored by the policy of RMB internationalization had disproportionate shares in global RMB trading. Over the following three years, RMB trading seemed to converge to the spatial pattern of all currencies, with a half-life of seven to eight years. The previously most traded emerging market currency, the Mexican peso, shows a similar pattern, although it is converging to the global norm more slowly. Three other emerging market currencies show a qualitatively similar evolution in the geography of their offshore trading. Overall, the RMB's internationalization is tracing an arc from the influence of administrative measures to the working of market forces. | Yin-Wong Cheung Robert N McCauley Chang Shu | 2019 | China & World Economy2019，27，5： | 3 |
| 7 | Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis显示文摘 | Rayner Katey J Sheedy Frederick J Esau Christine C Hussain Farah N Temel Ryan E Parathath Saj van Gils Janine M Rayner Alistair J Chang Aaron N Suarez Yajaira Fernandez-Hernando Carlos Fisher Edward A Moore Kathryn J | 2011 | Journal of Clinical Investigation2011，，7： | 2 |
| 8 | 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 |
| 9 | Cytokine imbalance in irritable bowel syndrome: a systematic review and meta‐analysis显示文摘 | M. Bashashati N. Rezaei A. Shafieyoun D. P. McKernan L. Chang L. ?hman E. M. Quigley M. Schmulson K. A. Sharkey M. Simrén | 2014 | Neurogastroenterol. Motil2014，，7： | 2 |
| 10 | Six-month progression-free survival as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma patients receiving temozolomide显示文摘 | Polley MY Lamborn KR Chang SM Butowski N Clarke JL Prados M. | 2010 | 中国神经肿瘤杂志2010，8，1： | 2 |
| 11 | Robust and high-quality time-domain audio watermarking based on low-frequency amplitude modification 显示文摘 | LIE W N CHANG Li-chun | 2006 | IEEE Trans on Multimedia2006，8，1： | 1 |
| 12 | Properties and failure mechanisms of pinned composite lap joints in monotonic and cyclic tension 显示文摘 | CHANG P MOURITZ A P COX B N | 2006 | Composites Science and Technology2006，66，13： | 1 |
| 13 | Recent Advances in Therapy for Glioblastoma显示文摘 | Clarke J Butowski N Chang S | 2010 | Archives of Neurology2010，67，3： | 1 |
| 14 | Complications of radicalcystectomy for nonmuscle invasive disease:comparison with muscle in-vasive disease显示文摘 | Cookson M S Chang S S Wells N | 2003 | J Urol2003，169，1： | 1 |
| 15 | Idiopathic hypereosinophilia syn-drome with loeffler endocarditis,embolic cerebral infarction,and left hy-dranencephaly:a case report显示文摘 | Lin C H Chang W N Chua S | 2009 | Acta Neurol Taiwan2009，18，3： | 1 |
| 16 | The effect of the minimal length uncertainty relation on the density of states and the cosmological constant problem显示文摘 | L N CHANG | 2002 | Phys Rev2002，65，12： | 1 |
| 17 | Effect of adsorbents coated with titanium dioxide on the photocatalytic degradation of propoxur 显示文摘 | Lu MC Chen J N Chang K T etal | 1999 | Chemosphere1999，38，： | 1 |
| 18 | Standard model with gravity couplings显示文摘 | CHANG L N CHOPIN S | 1996 | Phys RevD1996，，： | 1 |
| 19 | Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomized, placebocontrolled, multicentre study (Iressa Survival Evaluation in Lung Cancer)显示文摘 | Thatcher N Chang A Parikh P | 2005 | Lancet2005，366，9496： | 1 |
| 20 | Protesaes for cell suicid : functions and regulation of caspase 显示文摘 | Chang HY Fujita N | 2000 | Microbiol Mol Biol Rev2000，64，45： | 1 |
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