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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 | Clarifying sub-genomic positions of QTLs for flowering habit and fruit quality in U.S. strawberry (Fragaria×ananassa) breeding populations using pedigree-based QTL analysis显示文摘The cultivated strawberry(Fragaria×ananassa)is consumed worldwide for its flavor and nutritional benefits.Genetic analysis of commercially important traits in strawberry are important for the development of breeding methods and tools for this species.Although several quantitative trait loci(QTL)have been previously detected for fruit quality and flowering traits using low-density genetic maps,clarity on the sub-genomic locations of these QTLs was missing.Recent discoveries in allo-octoploid strawberry genomics led to the development of the IStraw90 single-nucleotide polymorphism(SNP)array,enabling high-density genetic maps and finer resolution QTL analysis.In this study,breeder-specified traits were evaluated in the Eastern(Michigan)and Western(Oregon)United States for a common set of breeding populations during 2 years.Several QTLs were validated for soluble solids content(SSC),fruit weight(FWT),pH and titratable acidity(TA)using a pedigree-based QTL analysis approach.For fruit quality,a QTL for SSC on linkage group(LG)6A,a QTL for FWT on LG 2BII,a QTL for pH on LG 4CII and two QTLs for TA on LGs 2A and 5B were detected.In addition,a large-effect QTL for flowering was detected at the distal end of LG 4A,coinciding with the FaPFRU locus.Marker haplotype analysis in the FaPFRU region indicated that the homozygous recessive genotype was highly predictive of seasonal flowering.SNP probes in the FaPFRU region may help facilitate marker-assisted selection for this trait. | Sujeet Verma Jason D Zurn Natalia Salinas Megan M Mathey Beatrice Denoyes James F Hancock Chad E Finn Nahla V Bassil Vance M Whitaker | 2017 | Horticulture Research2017，4，1： | 10 |
| 3 | 直接评估吗啡刺激糖尿病人隐静脉内皮一氧化氮释放减少显示文摘to directly measure in real time basal and stimulated levels of NO released from human saphenous vein endothelium and to quantify the expression of the μopiate receptor, which has been linked with NO release. METHODS: Saphenous vein segments from patients with type 2 diabetes ( n = 12) and patients without diabetes (n =8) were obtained. The release of NO was measured directly from the endothelium using a NO-specific amperometric probe. NΩ-nitro-L-arginine methyl ester (L-NAME, 0.1 mmol/L), a NO synthase (NOS) inhibitor, or morphine (1 μmol/L), a stimulant, was administered and the measurements were repeated. Values were reported relative to the mean initial measurement of NO release from diabetic endothelium, which was defined as the relative zero level of NO release. A RT-PCR was then performed on the endothelium to measureμ opiate receptor expression. RESULTS: Diabetic patients (n = 12) showed a relative and significantly diminished basal level of released NO, (0.049± 0.012) nmol/L, compared | Thomas V BILHNGER, James A VOSSWINKEL, Patrick CADET, Christos M RIALAS, Harold I MAGAZINE, George B STEFANO(Division of Cardiothoracic Surgery, Department of Surgery, University Hospital and Medical Center, HSC, T19-080, Stony Brook, New York 11794-8191 Neuroscience Research Institute, State University of New York College at Old Westbury, Old Westbury, New York , USA) | 2002 | Acta Pharmacologica Sinica2002，23，2： | 3 |
| 4 | Ankle Fractures in the Elderly: What You Get Depends on Where You Live and Who You See显示文摘 | Kenneth J Koval Jon Lurie Weiping Zhou Michael B Sparks Robert V Cantu Scott M Sporer James Weinstein | 2005 | Journal of Orthopaedic Trauma2005，，9： | 2 |
| 5 | Clay nanolayer reinforcement of cis-1,4-polyisoprene and epoxidized natural rubber 显示文摘 | Yen V James M | 2001 | J Appl Polym Sci2001，82，6： | 1 |
| 6 | Characterization of Phytophthora infestans in Wisconsin from 1993 to 1995显示文摘 | Marshall-Farm K D Mcgrath M James R V | 1998 | Plant Disease1998，82，4： | 1 |
| 7 | 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 |
| 8 | Seismic Response of Building Frames with Vertical Structural Irregularities 显示文摘 | Eggert V Valmundsson James M Nau | 1997 | Journal of Structural Engineering1997，123，1： | 1 |
| 9 | Thermoeconomics applied to an air conditioning system with cogeneration 显示文摘 | Tozer R Serrano M A L Capilla A V James R | 1996 | Building Sero Eng Res Tech1996，17，1： | 1 |
| 10 | The Pathfinder AVHRR land data set:An improved coarse resolution data set for terrestrial monitoring显示文摘 | James M E Kalluri S N V | 1994 | International Journal of Remote Sensing1994，15，17： | 1 |
| 11 | Clay nanolayer reinforcement of cis-1,4- polyisoprene and epoxidized natural rubber显示文摘 | Yen V James M | 2001 | J Appl Polym Sci2001，82，6： | 1 |
| 12 | Clay nanoclayer reinforcement ofc/s-1,4-polyisoprene and epoxidized natural rubber显示文摘 | YEN V JAMES M | 2001 | J Appl Polym Sci2001，82，6： | 1 |
| 13 | Seismic behavior and modeling of high-strength composite concrete-filled steel tube beam-columns显示文摘 | Amit H V James M R Richard S | 2002 | Journal of Constructional Steel Research2002，58，7： | 1 |
| 14 | Limiting the permea- bility of composites for cryogenic application 显示文摘 | Bechel V Negilski M James J | 2006 | Composites Sci- ence and Technology2006，66，： | 1 |
| 15 | Recent advance in techniques for hyperspectral image processing显示文摘 | Antonio P Jon A B Joseph W B Jason B Lorenzo B Gustavo C V Jocelyn C Mathieu F Paolo G Anthony G Mattia M James C T Giovanna T | 2009 | Remote Sensing of Environment2009，113，： | 1 |
| 16 | The pathfinder AVHRR land data set: An improved coarse resolution data set for terrestrial monitoring 显示文摘 | James M E Kalluri S N V | 1994 | International Journal of Remote Sensing1994，15，17： | 1 |
| 17 | Measuring quaternary ammonium cleaning agents with ion selective electrodes 显示文摘 | MICHAEL A P BERNARD J V JAMES M M | 2006 | Analytica Chimica Acta2006，570，2： | 1 |
| 18 | Improved sense-amplifier-based flip-flop:Design and measurements显示文摘 | NIKOLIC B OKLOBDZIJA V G STOJANOVIC V JIA W Y JAMES K C MING-TAK L M | 2000 | IEEE Journal of Solid-State Circuits2000，35，6： | 1 |
| 19 | A mechanistic explanation for pH-dependent ambient aquatic toxicity of Prymnesium parvum Carter显示文摘 | Valenti T W Jr James S V Lahousse M J | 2010 | Toxicon2010，55，5： | 1 |
| 20 | Copper solubility in Myersville B horizon soil in the presence of DTPA显示文摘 | JAMES B R | 1997 | Soil Science Society of America Journal1997，61，： | 1 |
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