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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 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 3 | Single-atom heterogeneous catalysts based on distinct carbon nitride scaffolds显示文摘Carbon nitrides integrating macroheterocycles offer unique potential as hosts for stabilizing metal atoms due to their rich electronic structure. To date, only graphitic heptazine-based polymers have been studied.Here, we demonstrate that palladium atoms can be effectively isolated on other carbon nitride scaffolds including linear melem oligomers and poly(triazine/heptazine imides). Increased metal uptake was linked to the larger cavity size and the presence of chloride ions in the polyimide structures. Changing the host structure leads to significant variation in the average oxidation state of the metal, which can be tuned by exchange of the ionic species as evidenced by X-ray photoelectron spectroscopy and supported by density functional theory. Evaluation in the semi-hydrogenation of 2-methyl-3-butyn-2-ol reveals an inverse correlation between the activity and the degree of oxidation of palladium, with oligomers exhibiting the highest activity. These findings provide new mechanistic insights into the influence of the carbon nitride structure on metal stabilization. | Zupeng Chen Evgeniya Vorobyeva Sharon Mitchell Edvin Fako Núria López Sean M.Collins Rowan K.Leary Paul A.Midgley Roland Hauert Javier Pérez-Ramírez | 2018 | National Science Review2018，5，5： | 4 |
| 4 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 5 | syndromes显示文摘 | Quilici j Banzet N Paule P Circulating endothelial cell count as a diagnostic marker for non-ST-elevation acute coronary | 2004 | Circulation2004，110，10： | 1 |
| 6 | Causes of failure and repai- ring options for dies and molds: A review 显示文摘 | Jhavar S Paul C P Jain N J | 2013 | Engineer- ing Failure Analysis2013，34，： | 1 |
| 7 | The nature of porosity in organic-rich mudstones of the Upper Jurassic Kimmeridge Clay Formation,North Sea,offshore United Kingdom显示文摘 | Fishman N S Paul C Hackley P C | 2012 | International Journal of Coal Geology2012，103，： | 1 |
| 8 | HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance显示文摘 | Paul P Rouas-Freiss N Khalil-Daher I | 1998 | Proc Natl Acad Sci USA1998，95，8： | 1 |
| 9 | HLA-G, -E, -F preworkshop:tools and protocols for analysis of non-classical class Ⅰ genes transcription and protein expression显示文摘 | Paul P Rouas-Freiss N Moreau P | 2000 | Hum Immunol2000，61，11： | 1 |
| 10 | Circulating endothelial cell count as a diagnostic marker for non - ST - elevation acute coro- nary syndromes显示文摘 | Quilici J Banzet N Paule P | 2004 | Circulatlon2004，110，51： | 1 |
| 11 | Utilization of fermented silkworm pupae silage in feed for carps显示文摘 | RANGACHARYULU P V GIRI S S PAUL B N | | 0，，01： | 1 |
| 12 | Selective catalytic oxidation显示文摘 | KATRYNIOK B KIMURA H SKRZYIiSKA H GIRARDON J S FONGARLAND P CAPRON M DUCOULOMBIER R MIMURA N PAUL S DUMEIGNIL F | 2011 | Green Chem2011，13，8： | 1 |
| 13 | 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 |
| 14 | Ideal and perfect hierar- chical secret sharing schemes 显示文摘 | Tentu A N Paul P Venkaiah V Ch | 2013 | IACR Cryptology ePrint Archive2013，，： | 1 |
| 15 | HIA-G,-E,-F preworkshop:took and protocolsfor anelysisof non-classical class I genestranscrition and protein expression显示文摘 | Rouas-Freiss N Moreau P et e1 | 2000 | Hum Immunol2000，61，11： | 1 |
| 16 | Atmospheric carbon dioxide concentrations over the past 60 million years显示文摘 | Paul N P Martin R P | | 0，，17： | 1 |
| 17 | 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 |
| 18 | HLA-G expression in melanoma:a way for cells to escape from immunosurveillance显示文摘 | Paul P Rous Freiss N Khalil Daher Ⅰ | 1998 | Proc Natl Acad Sci1998，95，8： | 1 |
| 19 | HLA-G:a tolerance molecule from the major histocompatibility complex显示文摘 | CAROSELLA E D ROUAS FREISS N PAUL P | 1999 | Immunol Today1999，20，60： | 1 |
| 20 | On the choice of heteronuclear dipolar decoupling scheme in solid-state NMR显示文摘 | Paul S Kurur N D Madhu P K | 2010 | J Magn Reson2010，207，1： | 1 |
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