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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 | 如何设计高质量针刺临床研究:基于证据的专家共识显示文摘本针刺随机对照试验(Randomised controlled trials, RCT)专家共识是基于目前针刺试验面临的最普遍、最关键问题,由临床医生、研究人员、从事针灸和外科的临床试验专家、统计专家、临床流行病学和方法学专家以及患者组成的国际临床研究小组联合制订。该共识将有助于临床试验资助者、注册者以及期刊编辑等评估针刺RCT方案及研究结果的相关性、重要性和质量。 | 张誉清 焦睿珉 Claudia M Witt 劳力行 刘建平 Lehana Thabane Karen J Sherman Mike Cummings Dawn P Richards Eun-Kyung Anna Kim Tae-Hun Kim Myeong Soo Lee Michael E Wechsler Benno Brinkhaus Jun J Mao Caroline A Smith 岗卫娟 刘保延 刘志顺 刘岩 郑晖 吴佳霓 AloBSO Carrasco-Labra Mohit Bhandari Philip J Devereaux 景向红 Gordon Guyatt | 2022 | 英国医学杂志中文版2022，25，6： | 7 |
| 3 | Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4显示文摘 | Jan Kramer Claudia Hegert Kaomei Guan Anna M Wobus Peter K Müller Jürgen Rohwedel | 2000 | Mechanisms of Development2000，，2： | 2 |
| 4 | Allogeneic partially HLA-matched dendritic cells pulsed with autologous tumor cell lysate as a vaccine in metastatic renal cell cancer显示文摘 | Anne Fl?rcken Joachim Kopp Antje van Lessen Kamran Movassaghi Anna Takvorian Korinna J?hrens Markus M?bs Constanze Sch?nemann Birgit Sawitzki Karl Egerer Bernd D?rken Antonio Pezzutto J?rg Westermann | 2013 | Human Vaccines & Immunotherapeutics2013，，： | 2 |
| 5 | Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones显示文摘AIM An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid components of hepatic and gallbladder bile and its viscosity in patients with gallstones.METHODS Viscosity of bile ( mpa. s ) wasmeasured using rotation viscosimetry in regard to the non-Newtonian property of bile at law shear rates.RESULTS Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 ± 0.60 mpa. s, mean ± SEM, n --28) and mixed stones (3.50±0.68 mPa. s; n =8) compared to hepatic bile (0.92 ± 0.06 mpa. s,n -6). A positive correlation between mucin and viscosity was found in gallbladder biles (r=0.65; P<0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P<0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles.CONCLUSION The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones. | Dieter Jüngst Anna Niemeyer Iris Müller Benedikta Zündt Günther Meyer Martin Wilhelmi Reginalddel Pozo | 2001 | World Journal of Gastroenterology2001，7，2： | 2 |
| 6 | 向在人的察觉到钙的受体的 allosteric 药的结构的理解显示文摘allosterically 指向人的察觉到钙的受体(CaSR ) 的药有实质的治疗学的潜力,但是当前被限制。给 CaSR 的高分辨率的结构的缺席,我们把 mutagenesis 与一条新奇分析途径并且开发 “ 的分子的建模相结合; enriched”为在 Ca 2+ 在 CaSRs 7 transmembrane (7TM ) 以内的 o 和 allosteric 调节的人领域。修改多重有约束力的地点以适应在结构上的一个扩大的洞多样的 ligands 被识别。Phenylalkylamines 绑在与通常认为的 Ca 2+ o -binding 地点并且向一个细胞外的门厅延长。相反,在结构上和 pharmacologically 不同的 AC-265347 在 7TM 领域以内更深绑。而且,不同氨基酸网络被发现调停由不同调节的人的 cooperativity。这些调查结果可以与不同、潜在地偏导小径的药理学效果便于 allosteric 调节的人的合理设计。 | Katie Leach Karen J Gregory Irina Kufareva Elham Khajehali Anna E Cook Ruben Abagyan Arthur D Conigrave Patrick M Sexton Arthur Christopoulos | 2016 | Cell Research2016，26，5： | 2 |
| 7 | Inosito1 steroisomer stebilize an oligom etric aggregate of Alzhemier amyloid β-induced toxicity显示文摘 | Joanne M Rirka G Anna J et a1 | 2000 | Biol Chem2000，275，18： | 1 |
| 8 | Ultrastructural organization and micromechanical properties of shark tooth enameloid显示文摘 | Joachim E Anna M J Dierk R | 2014 | Acta Biomaterialia2014，10，9： | 1 |
| 9 | Atom transfer radical polymerization of methyl acrylate from a multifunctional initiator at ambient temperature显示文摘 | ANNA C ROBERT V EVA M J | 2002 | Polymer2002，43，： | 1 |
| 10 | Structure and correlations of the flux line lattice in crystalline Nb through the peak effect显示文摘 | Gammel P L Yaron U Ramirez A P Bishop D J Chang A M Ruel R Pfeiffer L N Bucher E D'Anna G Huse D A Mortensen K Eskildsen M R Kes P H | | 0，，： | 1 |
| 11 | Development of complete hydrolysis of pectins from apple pomace显示文摘 | AGNIESZKA W MAGDALENA M ANNA S J | 2015 | Food Chemistry2015，172，： | 1 |
| 12 | Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection显示文摘 | Shi Guanfang Field David J Ko Kyung-ae Ture Sara Srivastava Kalyan Levy Scott Kowalska M Anna Poncz Mortimer Fowell Deborah J Morrell Craig N | 2014 | Journal of Clinical Investigation2014，，： | 1 |
| 13 | The impact of experiential consumption cognitions and emotions on behavioural intentions 显示文摘 | Enrique Bigne J Enrique M Anna S | 2008 | Journal of Services Marketing2008，22，4： | 1 |
| 14 | A nongradient based algorithm for the determination of surface tension from a pendant drop:Application to low Bond number drop shapes显示文摘 | ALVAREZ N J WALKER L M ANNA S L | | 0，，2： | 1 |
| 15 | Effeet of eider maturation on the chemical and sensory characteristics of fresh eider spirits显示文摘 | Roberto R M Anna P L Juan J M A | 2010 | Food Research International2010，43，： | 1 |
| 16 | Revisiting the simplified bernouUi equation 显示文摘 | Heys Jeffrey J Holyoak Nicole Calleja Anna M | 2010 | The Open Biomedical Engineering Journal2010，4，： | 1 |
| 17 | Effect of body image on pregnancy weight gain显示文摘 | Ushma J M Anna M S Amy H H | 2011 | Matem Child Health J2011，15，1： | 1 |
| 18 | Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin显示文摘 | H anna J Wernig M Markoulaki S | 2007 | Sience2007，318，： | 1 |
| 19 | Gas chromatography of methylderivative sofnaturally occurring capeaicinoids显示文摘 | ANNA M JOHN J | 1987 | J Chromatogr1987，409，： | 1 |
| 20 | Twist and snail expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression显示文摘 | Anna J M Mervi N M Ylermi S | 2011 | BMC Cancer2011，11，： | 1 |
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