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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 | Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice显示文摘AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with S.mansoni proteins.Experiments were performed 5 d after TNBS injection.Inflammationwas quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo gastrointestinal motility.Peristaltic activity of distal colonic segments was studied in vitro using a modified Trendelenburg set-up.Cytokine profiles of T-lymphocytes isolated from the colon were determined by real time reverse transcriptase-polymerase chain reaction. RESULTS:Intracolonic injection of TNBS caused severe colitis.Treatment with S.mansoni proteins significantly ameliorated colonic inflammation after 5 d.TNBS did not affect gastric emptying but significantly decreased the geometric center and impaired colonic peristaltic activity 5 d after the induction of colitis.Treatment with S.mansoni proteins ameliorated these in vivo and in vitro motility disturbances.In addition,TNBS injection caused a downregulation of effector T cell cytokines after 5 d,whereas a S.mansoni protein effect was no longer observed at this time point. CONCLUSION:Treatment with S.mansoni proteins attenuated intestinal inflammation and ameliorated motility disturbances during murine experimental colitis. | Nathalie E Ruyssers Benedicte Y De Winter Joris G De Man Natacha D Ruyssers Ann J Van Gils Alex Loukas Mark S Pearson Joel V Weinstock Paul A Pelckmans Tom G Moreels | 2010 | World Journal of Gastroenterology2010，16，6： | 11 |
| 3 | 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 |
| 4 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 5 | Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial显示文摘 | Jeanin E van Hooft Willem A Bemelman Bas Oldenburg Andreas W Marinelli Martijn F Lutke Holzik Marina J Grubben Mirjam A Sprangers Marcel G Dijkgraaf Paul Fockens | 2011 | Lancet Oncology2011，，4： | 3 |
| 6 | Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression显示文摘 | Victoria G Weis Josane F Sousa Bonnie J LaFleur Ki Taek Nam Jared A Weis Paul E Finke Nadia A Ameen James G Fox James R Goldenring | 2013 | Gut2013，，9： | 3 |
| 7 | Nitrogen-linked diphosphine ligands with ethers attached to nitrogen for chromium-catalyzed ethylene ti- and tetramerizations显示文摘 | Paul R E Cassandra M Pringle P G | 2006 | Organometallics2006，25，22： | 1 |
| 8 | Kinematics Control Equations for Simple Manipulator显示文摘 | Paul R P Shirnanno B E Mayer G | 1981 | IEEEE Trans SMC1981，11，6： | 1 |
| 9 | Molecular insights into Burkholderia pseudomaUei and Burkholderia mallei patho- genesis显示文摘 | EDOUARD E G PAUL J B DAVID D | 2010 | Annu Rev Microbiol2010，64，： | 1 |
| 10 | Investigation of Self- Starting Capability of Vertical Axis Wind Turbines Using a Computational Fluid Dynamics Approach显示文摘 | Alexandrina Untaroiu Houston G Wood Paul E Allaire | 2011 | J Sol Energy Eng2011，133，04： | 1 |
| 11 | Effect of pair-housing on operant behavior task performance by rhesus monkeys显示文摘 | Hotchkiss C E Paule M G | 2003 | Contemp Top Lab Anim Sci2003，42，4： | 1 |
| 12 | Increasing rates of cardiac device infections among medicare beneficiaries: 1990–1999显示文摘 | Christopher H Cabell Paul A Heidenreich Vivian H Chu Christopher M Moore Martin E Stryjewski G.Ralph Corey Vance G Fowler | 2004 | American Heart Journal2004，，4： | 1 |
| 13 | Reforestation and topography affect montane soil properties, nitrogen pools, and nitrogen transformations in Hawaii 显示文摘 | Paul G Scowcroft Janis E Haraguchi Nguyen V Hue | 2004 | Soil Science Society of American Journal2004，68，： | 1 |
| 14 | Regulatory role of SGTI in early R Gene-Mediated plant defenses显示文摘 | Mark J Paul M Katherine K Bart J Jonathan D G Jane E | 2002 | Science2002，295，15： | 1 |
| 15 | Inhibitor - resistant TEM β - lactamase : Phenotypic, genetic, and biochemical characteristics 显示文摘 | Chaibi E B Sirot D Paul G | 1999 | J Antimicrob Chemother1999，43，： | 1 |
| 16 | Effective Costs and Chemical Use in United States Agricultural Production: Using the Environ- ment as a 'Free' Input显示文摘 | Paul C Ball V E Fehhoven R G ct al | 2002 | American Journal of Agricultural Economics2002，84，4： | 1 |
| 17 | Molecular detection of prostate cancer in urine by GSTP1 hypermethylation显示文摘 | PAUL C MANEL E JAMES G | 2001 | Clinical cancer research2001，7，9： | 1 |
| 18 | Kinematics control equations for simple manipulators显示文摘 | Paul R P Shimano B E Mayer G | 1981 | IEEE Trans SMC1981，11，6： | 1 |
| 19 | Kinematic control equations for simple manipulators显示文摘 | Paul R P Shimano B Mayer G E | 1981 | IEEE Transactions on Systems Man and Cybernetics1981，11，6： | 1 |
| 20 | The impact of hepatitis C virus coinfection on HIV-related kidney disease: a systematic review and meta-analysis显示文摘 | Christina M Wyatt Carlos Malvestutto Steven G Coca Paul E Klotman Chirag R Parikh | 2008 | AIDS2008，，14： | 1 |
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