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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 | High-density SNP-based genetic maps for the parents of an outcrossed and a selfed tetraploid garden rose cross, inferred from admixed progeny using the 68k rose SNP array显示文摘Dense genetic maps create a base for QTL analysis of important traits and future implementation of marker-assisted breeding.In tetraploid rose,the existing linkage maps include<300 markers to cover 28 linkage groups(4 homologous sets of 7 chromosomes).Here we used the 68k WagRhSNP Axiom single-nucleotide polymorphism(SNP)array for rose,in combination with SNP dosage calling at the tetraploid level,to genotype offspring from the garden rose cultivar‘Red New Dawn’.The offspring proved to be not from a single bi-parental cross.In rose breeding,crosses with unintended parents occur regularly.We developed a strategy to separate progeny into putative populations,even while one of the parents was unknown,using principle component analysis on pairwise genetic distances based on sets of selected SNP markers that were homozygous,and therefore uninformative for one parent.One of the inferred populations was consistent with self-fertilization of‘Red New Dawn’.Subsequently,linkage maps were generated for a bi-parental and a self-pollinated population with‘Red New Dawn’as the common maternal parent.The densest map,for the selfed parent,had 1929 SNP markers on 25 linkage groups,covering 1765.5 cM at an average marker distance of 0.9 cM.Synteny with the strawberry(Fragaria vesca)genome was extensive.Rose ICM1 corresponded to F.vesca pseudochromosome 7(Fv7),ICM4 to Fv4,ICM5 to Fv3,ICM6 to Fv2 and ICM7 to Fv5.Rose ICM2 corresponded to parts of F.vesca pseudochromosomes 1 and 6,whereas ICM3 is syntenic to the remainder of Fv6. | Mirjana Vukosavljev Paul Arens Roeland E Voorrips Wendy P C van't Westende G D Esselink Peter M Bourke Peter Cox W Eric van de Weg Richard G F Visser Chris Maliepaard Marinus J M Smulders | 2016 | Horticulture Research2016，3，1： | 6 |
| 3 | 动态88小时:美国地质调查局国家地震信息中心对2011年3月11日M_W9.0日本地震的响应显示文摘引言
2011年3月11日日本本州岛东海岸附近海域发生的M9.0地震(Tohoku earthquake,以下称“东日本大地震”——译者注)及其引发的海啸造成数以万计的人员死亡,造成的财产损失可能超过1万亿美元,这是有历史记录以来最严重的自然灾害之一。 | Gavin P Hayes Paul S Earle Harley M Benz David J Wald Richard W Briggs 左玉玲(译) 郑需要(校) | 2011 | 国际地震动态2011，，8： | 4 |
| 4 | 轮胎工业用更安全的操作油显示文摘在欧洲 ,立法和公众压力正在使欧洲市场上的操作油性质发生变化。这引起欧洲橡胶行业对不使用有潜在致癌危险芳香油的新型轮胎和橡胶配方进行评述。本文对这一状况进行了研究 ,并探讨了美国市场上可能出现的动态 ,介绍了不同产品的需求量以及北美操作油和润滑基油制造不断变化的局面。 | Paul W H T Juergen E P 吴淑华 | 2002 | 轮胎工业2002，22，5： | 3 |
| 5 | Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial显示文摘 | David W Andrews Charles B Scott Paul W Sperduto Adam E Flanders Laurie E Gaspar Michael C Schell Maria Werner-Wasik William Demas Janice Ryu Jean-Paul Bahary Luis Souhami Marvin Rotman Minesh P Mehta Walter J Curran | 2004 | The Lancet . 2004 (9422)2004，，9422： | 2 |
| 6 | Anaerobic bacteria and intrahepatic stones: detections of Clostridium sp. and Bacteroides fragilis显示文摘To detect anaerobic bacteria Clostridium sp . and Bacteroides fragilis in intrahepatic stones by molecular genetic method Methods DNA was extracted from 59 stone samples and subjected to polymerase chain reaction (PCR) amplification targeting the 16S rRNA gene of Clostridium sp . and the glutamine synthetase gene of Bacteroides fragilis Single-strand conformational polymorphism (SSCP) analysis was performed to identify the Clostridium sp Results 16S rRNA gene sequences for Clostridium sp. were identified in 49 stones (83%, 49/59) The two most common groups were detected in 19 (41%) and 17 (37%) of the 46 samples using SSPC analysis, and 25/59 (42%) stones were tested positive for Bacteroides fragilis Conclusions Anaerobes such as Clostridium sp and Bacteroides fragilis present in intrahepatic stones and may play a role in stone formation PCR is a useful technique to detect fastidious pathogens, which are difficult to culture SSCP of PCR products is a rapid method in differentiating bacterial | LIU Yanlei Kan Lam Yajarayma J Tang Paul H Gumerlock Dong Ki Lee Myung Hwa Kim Sum P Lee Joseph SilvaJr Joseph W Leung | 2000 | Chinese Medical Journal2000，，9： | 2 |
| 7 | Plant volatiles as a defense against insect herbivores 显示文摘 | PAUL W P JAMES H T | 1999 | Plant Physiology1999，121，： | 1 |
| 8 | Evidence for the replication of bovineleukemia virus in the B-lymphocytes显示文摘 | Paul P S,Pomerey K A,Johnson D W, | | Am J Vet Res,1 9770，38，873： | 1 |
| 9 | Review of position-sensorless operation of brushless permanent-magnet machines显示文摘 | Paul P A John F W | 2006 | IEEE Transactions on Industrial Electronics2006，53，2： | 1 |
| 10 | Late paleocene to eocene paleocenography of the equatorial pacific ocean: stable isotopes recorded at ocean drilling program site 865, allison guyot显示文摘 | Zachos J C Thomas E Parrow M Paul C K Kelly D C Silva I P Sliter W V Lohmann K C | 1995 | Paleoceanography1995，10，： | 1 |
| 11 | Combination of DOM With LES in a Gas Turbine Combustor 显示文摘 | Jones W P Paul M C | 2005 | International Journal of Engineering Science2005，43，： | 1 |
| 12 | Prehistoric and modem freshwater mussel (bivalvia:unionoidea) faunas of the Tennessee River:Alabama,Kentucky,and Tennessee显示文摘 | Mark H H Paul W P | 1999 | Regulated Rivers:Research & Management1999，15，13： | 1 |
| 13 | Development of a vibrating cassava root harvester显示文摘 | Gupta C P Stevens W F Paul S C | 1999 | Agricultural Mechanization in Asia Africa and Latin America1999，30，1： | 1 |
| 14 | Nitrationby oxides of nitrogen, Part 4: Unexpected behav-ior of certain aziridines and azetidines upon reac-tion with dinitrogen pentoxide显示文摘 | Golding P Millar R W Paul N C | 1991 | Tetralled Lett1991，32，37： | 1 |
| 15 | Chitin and chitosan polymers : Chemistry, solubility and fiber formation 显示文摘 | Pillai C K S Paul W Sharma C P | 2009 | Progress in Polymer Science2009，34，： | 1 |
| 16 | Characterization of Φ12,a bacteriophage related to Φ6:nucleotide sequence of the large double-stranded RNA显示文摘 | Paul G Christiaan P Hui W | 2002 | Virology2002，295，2： | 1 |
| 17 | Tillage effects on soil properties and crop production in the sub-humid and semiarid Argentinean Pampas 显示文摘 | Daniel E B Jose L P Paul W U | 1998 | Soil & Tillage Res1998，49，： | 1 |
| 18 | Global lithium resources : relative importanceof pegmatite,brine and other deposits 显示文摘 | Stephen E Kealer Paul W Gruber Pablo A Medina Gregory A Keoleian Mark P Everson Timothy J Wall-ington | 2012 | Ore GeologyReviews2012，48，： | 1 |
| 19 | Deepwater Remains Immature Frontier显示文摘 | Henry S P Paul W | 2002 | Offshore2002，62，10： | 1 |
| 20 | Unexpected behaviour of certain aziridines and azetidines upon reaction with dinitrogen pentoxide 显示文摘 | Golding P Millar R W Paul N C | 1991 | Tetrahed Letters1991，32，37： | 1 |
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