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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酒精摄入、心脏生物标志物和心房颤动风险与不良结局显示文摘酒精摄入和新发心房颤动相关性证据不一,尤其是在低剂量下。该研究评估欧洲队列在整个饮酒范围内酒精摄入、生物标志物和新发心房颤动的关系。方法和结果:在一个以社区为基础的汇集队列中,研究者随访107845人,以评估酒精摄入(酒精种类和饮酒方式)与新发心房颤动的关系。研究者收集经典心血管病危险因素和新发心力衰竭的信息,并检测生物标记物氨基末端脑钠肽前体和高敏肌钙蛋白I。陈嘉睿(译) 练桂丽((审校) Csengeri D Sprünker NA Di Castelnuovo A Niiranen T Vishram-Nielsen JK Costanzo S S derberg S Jensen SM Vartiainen E Donati MB Magnussen C Camen S Gianfagna F L chen ML Kee F Kontto J Mathiesen EB Koenig W Stefan B de Gaetano G J rgensen T Kuulasmaa K Zeller T Salomaa V Iacoviello L Schnabel RB 2021中华高血压杂志2021,29,2:9
3High-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 2016Horticulture Research2016,3,1:6
4高危心血管病老年人血压变异性的相关因素显示文摘诊问血压变异性是心血管病的独立预测因素。该研究探讨老年人血压变异的相关因素。方法:在普伐他汀干预高危老年人的前瞻性研究( pravastatin inelderly individuals at risk of vascular disease, PROS-PER)中,分析70~82岁有心血管病史或危险因素的男性和女性者3794人。Poortvliet RK Lloyd SM Ford I Sattar N de Craen AJ Wijsman LW Mooijaart SP Westendorp G Jukema JW de Ruijter W Gussekloo J Stott DJ 2015中华高血压杂志2015,23,10:3
5Coronary artery disease in congenital single coronary artery in adults:A Dutch case series显示文摘AIM:To assess the current diagnostic and therapeutic management and the clinical implications of congenital single coronary artery(SCA) in adults.METHODS:We identified 15 patients with a SCA detected from four Dutch angiography centers in the period between 2010 and 2013.Symptomatic patients who underwent routine diagnostic coronary angiography(CAG) for suspected coronary artery disease and who incidentally were found to have isolated SCA were analyzed.RESULTS:Fifteen(7 females) with a mean age of 58.5 ± 13.78 years(range 43-86) had a SCA.ConventionalCAG demonstrated congenital isolated SCA originating as a single ostium from the right sinus of Valsalva in 6 patients and originating from the left in 9 patients.Minimal to moderate coronary atherosclerotic changes were found in 4,and severe stenotic lesions in another 4 patients.Seven patients were free of coronary atherosclerosis.Runs of non-sustained ventricular tachycardia were documented in 2 patients,one of whom demonstrated transmural ischemic changes on presentation.Myocardial perfusion scintigraphic evidence of transmural myocardial ischemia was found in 1 patient due to kinking and squeezing of the SCA with an interarterial course between the aorta and pulmonary artery.Multi-slice computed tomography(MSCT) was helpful to delineate the course of the anomalous artery relative to the aorta and pulmonary artery.Percutaneous coronary intervention was successfully performed in 3 patients.Eight patients were managed medically.Arterial bypass graft was performed in 4 patients with the squeezed SCA.CONCLUSION:SCA may be associated with transient transmural myocardial ischemia and aborted sudden death in the absence of coronary atherosclerosis.The availability and sophistication of MSCT facilitates the delineation of the course of a SCA.We present a Dutch case series and review of the literature.Salah AM Said Willem G de Voogt Suat Bulut Jacques Han Peter Polak Rogier LG Nijhuis Jeroen W op den Akker Andries Slootweg 2014World Journal of Cardiology2014,6,4:3
6查看详情显示文摘Derbyshire F J De Beer V H J Abotsi G M K Scaroni A W, Solar J M, Skrovanek D J 0,,:2
7Statins 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 2010The Lancet2010,,9716:2
8Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting显示文摘瞄准:如果与推延的 portasystemic 有关的 T 房间激活通过 RANKL 依赖的小径引起调停骨破折的骨头损失,学习。如果用 rapamycin 的 T 房间抑制将在老鼠免于骨头损失,我们也调查了。方法:推延的 Portasystemic 在男 Sprague-Dawley 老鼠和 rapamycin 被执行 0.1 mg/kg 被管饲法为 15 wk 管理。老鼠收到了 powderized 食物并且补加喂在骨头作文上阻止营养不良的效果。重量获得和生长在推延的动物在外科以后被恢复。在结束,骨头周转和量的骨头组织学的生物化学的参数被估计。T 房间激活,煽动性的 cytokine 生产,和 RANKL 依赖的小径的标记被测量。另外, IGF-1 和性腺机能减退的角色被调查。结果:推延的 Portasystemic 引起了是 RANKL 独立人士的低周转骨质疏松症。包括 IL-1, IL-6 和 TNFalpha,骨头再吞 cytokine 层次没在浆液和 TNFalpha 被增加, RANKL 表示不起来在 PBMC 调整了。推延的 Portasystemic 增加了传播 CD8+T 房间人口。Rapamycin 减少了传播 CD8+T 房间人口,增加了 CD8+CD25+T 规章的房间人口并且改进了骨头周转的所有参数。结论:推延的 portasystemic 引起的骨质疏松症可以被 rapamycin 部分在肝的骨营养不良的老鼠模型改善。Schalk W van der Merwe Maria M Conradie Robert Bond Brenda J Olivier Elongo Fritz Martin Nieuwoudt Rhena Delport Tomas Slavik Gert Engelbrecht Del Kahn Enid G Shephard Maritha J Kotze Nico P de Villiers Stephen Hough 2006World Journal of Gastroenterology2006,12,28:2
9Synthesis and characterization of homogeneous intermetallic Fe-Zn compounds显示文摘Gellings P J de Bree E W Gierman G 1979Z Metallkde1979,70,5:2
10脊髓损伤后残存自主神经功能载录国际标准显示文摘近年来,脊髓损伤神经学分类园际标准(International Stand- ards for the Neurological Classification of Spinal Cord Injury, ISNCSCI)被用来记载脊髓损伤后运动和感觉功能的损害,目前该标准已是第六版。1992年第一份国际认可的标准出版时,曾进行了较大的修订,修订内容包括完全性损伤与不完全性损伤的定义,MS Alexander AB Jackson W Donovan DE Graves SL Elliott A Krassioukov AW Sheel I Estoresl B Green A Gousse NL Braekett D Cardenas M Kennelly A-K Karlason F Biering-Sorensen K Krogh T Linsenmeyer R Marino J Ditunno CJ Mathias I Perkash G Creasey G Schilero J Wecht B Schurch V Dietz J Sonksen S Stiens D Bodner LA Wuermser J-J Wyndaele 周谋望 刘楠 S Charlifue 2010中华物理医学与康复杂志2010,32,4:2
11Statins 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 2010The Lancet2010,,9716:2
12Effects of elevated on photosynthesis in European forest species: a meta-analysis of model parameters 显示文摘Medlyn B E Badeck F W de Pury D G G 1999Plant Cell & Environment1999,22,:1
13Animal and temporal effects on ovarian follicular dynamics in Brahman heifers显示文摘Rhodes J M de Ath G Entwisfle K W 1995Anita Reprod Sci1995,38,:1
14Tailoring the swelling pressure of degrading dextran hydroxyethyl methacrylate hydrogels显示文摘Stubbe B G Horkay F Amsden B Hennink W E De Smedt S C Demeester J 2003Biomacro-molecules2003,4,:1
15Grinding of WC - Co hardmetals显示文摘HEGEMANJBJ W DE HOSSONJ Th M DE With G 2001Wear2001,,248:1
16Deregulation,Privatization,and Competition:Transmission Planning under Uncertainty显示文摘De la Torre T Feltes J W Roman T G S 1999IEEE Trans on Power Systems1999,14,2:1
17Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria 显示文摘Zoetendal E G Akkermans A D L De Vos W M 1998Applied and Environmental Microbiology1998,64,10:1
18Electric-field and temperature dependence of the hole mobility in poly (p-phenylene vinylene)显示文摘Blom P W M De Jong M J M Van Munster M G 1997Physical Review B1997,55,2:1
19Biomarkers of satiation and satiety 显示文摘DE G C BLOM W A SMEETS P A 2004Am J Clin Nutr2004,79,6:1
20Signal transduction by tumor necrosis factor and gene regulation of the inflamma- tory cytokine interleukin-6显示文摘Vanden Berghe W Vermeulen L De Wilde G 2000Biochem Phar- macol2000,60,8:1
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