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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 | Computed tomography overestimation of esophageal tumor length: Implications for radiotherapy planning显示文摘AIM:To assess the relationship between preoperative computed tomography(CT)and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.METHODS:A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy.Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens.Inter-and intra-observer variations in CT measurements were assessed.Survival data were collected.RESULTS:There was a weak correlation between CT and pathological tumor length(r=0.30,P=0.025).CT lengths were longer than pathological lengths in 68%(38/56)of patients with a mean difference of 1.67 cm(95%CI:1.18-2.97).The mean difference in measurements by two radiologists was 0.39 cm(95% CI:-0.59-1.44).The mean difference between repeat CT measured tumor length(intra-observer variation) were 0.04 cm(95%CI:-0.59-0.66)and 0.47 cm (95%CI:-0.53-1.47).When stratified,patients not receiving neoadjuvant chemotherapy showed a strong correlation between CT and pathological tumor length(r =0.69,P=0.0014,n=37)than patients that did(r= 0.13,P=0.43,n=19).Median survival with CT tumor length>5.6 cm was poorer than with smaller tumors,but the difference was not statistically significant.CONCLUSION:Esophageal tumor length assessed using CT does not reflect pathological tumor extent and should not be the only modality used for management decisions,particularly for planning radiotherapy. | Karim Sillah Luke R Williams Hans-Ulrich Laasch Azeem Saleem Gillian Watkins Susan A Pritchard Patricia M Price Catharine M West Ian M Welch | 2010 | World Journal of Gastrointestinal Oncology2010，2，4： | 10 |
| 3 | PLEIOTROPIC REGULATORY LOCUS 1 (PRL1) Integrates the Regulation of Sugar Responses with Isoprenoid Metabolism in Arabidopsis显示文摘在植物房间的 isoprenoids 的生合成从 mevalonate (MVA ) 在 cytosol 生产的先锋发生小径并且在由 methylerythritol 4 磷酸盐(MEP ) 的质体,小径,而是很少对协调两条小径的机制被知道。在 Arabidopsis thaliana 为如此的协作发信号的糖的重要性的证据被没有变化,在相关 MEP 小径抄本,蛋白质,或酶活动的层次显示出导出 MEP 的 isoprenoid 产品(叶绿素和类胡萝卜素) 的增加的累积的异种的描述这里提供。这异种被发现是新 loss-of-function 等位基因 PRL1 (多种的规章的地点 1 ) ,编码作为糖的一个全球管理者工作的保存 WD 蛋白质的基因,应力,和荷尔蒙回答,部分地由 SNF1 相关的蛋白质 kinases (SnRK1 ) 的抑制。与在 MVA 小径的主要的规章的酶的 phosphorylation 和 inactivation 的 SnRK1 kinases 的报导角色一致(hydroxymethylglutaryl 辅酶 -- reductase ) ,它的活动或蛋白质层次在 prl1 幼苗被减少。然而,导出 MVA 的结束产品(甾醇) 的累积在变异的幼苗是未改变的。蔗糖补充到野类型的幼苗 phenocopied prl1 变化以 isoprenoid 新陈代谢,建议观察 isoprenoid 显型从增加的糖累积导致 prl1 异种。在摘要, PRL1 看起来与糖,荷尔蒙,和压力回答协调 isoprenoid 新陈代谢。 | Ursula Flores-Perez Jordi Perez-Gil Marta Closa Louwrance R Wright Patricia Botella-Pavia Michael A. Phillips Albert Ferrer Jonathan Gershenzon Manuel Rodriguez-Concepcion | 2010 | Molecular Plant2010，3，1： | 5 |
| 4 | Induced pluripotent stem cells for modeling neurological disorders显示文摘Several diseases have been successfully modeled since the development of induced pluripotent stem cell(i PSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from i PSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific i PSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using i PSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, PhelanMc Dermid, Rett syndrome as well as Nonsyndromic Autism. | Fabiele B Russo Fernanda R Cugola Isabella R Fernandes Graciela C Pignatari Patricia C B Beltrão-Braga | 2015 | World Journal of Transplantation2015，5，4： | 4 |
| 5 | 选择性环氧化酶2抑制剂和传统非甾体抗炎药增加粥样血栓形成的风险吗?随机试验的荟萃分析显示文摘目的:评价选择性环氧化酶2(COX-2)抑制剂和传统的非甾体类抗炎药(NSMDs)在发生血管事件上的风险性。设计:对已发表和未发表随机试验的表格式资料进行荟萃分析,对传统 NSAIDs 的作用进行间接评估。资料来源:资料分别来源于 Medline 和 Embase(1966年1月至2005年4月);食品与药品管理局记录;以及诺华、辉瑞、默克公司的资料。回顾方法:符合以下条件的随机试验入组本研究:一种选择性 COX-2抑制剂与安慰剂比较或一种选择性 COX-2抑制剂与一种传统的 NSAID之间对比;用药持续时间至少4周;包含严重血管事件方面的信息,如心肌梗死、卒中或由于血管事件死亡。各个独立研究者和药厂为本研究提供了有关随机化的病人数目、血管事件的数目以及每个随机化小组中随访的人时(Person time)等信息。结果:在与安慰剂对比的试验中,选择性COX-2抑制剂使严重血管事件发生率增加42%(1.2%/年比0.9%/年;率比1.42,95%可信区间1.13~1.78;P=0.005);不同的选择性 COX-2抑制剂之间没有显著性差异。这主要归因于心肌梗死的风险增加(0.6%/年比0.3%/年;1.86,1.33~2.59;P=0.0003),在其他血管性事件上没有明显的区别。在为时至少1年的试验中(平均2.7年),血管事件的率比是1.45(1.12~1.89;P=0.005)。总的来说,严重血管事件的发生率在选择性 COX-2抑制剂和任何传统 NSAID 之间没有差异(1.0%/年比0.9%/年;1.16,0.97~1.38;P=0.1)。然而,在选择性 COX-2抑制剂与萘普生对比的试验(1.57,1.21~2.03)和选择性COX-2抑制剂与非萘普生类 NSAIDs 相比较的试验之间(0.88,O.69~1.12),我们发现了统计学差异。与安慰剂比较血管事件的总体比率如下:萘普生0.92(0.67~1.26),布洛芬1.51(0.96~2.37),双氯芬酸1.63(1.12~2.37)。结论:选择性 COX-2抑制剂可以中等度增加血管事件的风险性,大剂量布洛芬和双氯芬酸同样具有此作用,但大剂量萘普生不明显增加血管事件的风险性。 | Patricia M Kearney Colin Baigent Jon Godwin Heather Halls Jonathan R Emberson Carlo Patrono 徐东(译) 张卓莉(校) | 2006 | 英国医学杂志中文版2006，9，5： | 4 |
| 6 | Lactobacilli,bifi dobacteria and E.coli nissle induce pro-and anti-inflammatory cytokines in peripheral blood mononuclear cells显示文摘AIM: To investigate whether the stimulation of peripher- al blood mononuclear cells (PBMNC) with the cell debris and cell extraction of different probiotic strains is similar or species specifi c. METHODS: Three strains of bifi dobacteria, 4 strains of lactobacilli, and E. coli nissle were sonicated and centri- fuged in order to divide them into cell extract and cell debris. PBMNC were separated by density gradient and incubated for 36 h with either the cell debris or the cell extract of single strains of probiotic bacteria in doses from 102 to 108 CFU/mL. Cell supernatants were taken and interleukin (IL)-10, IL-1β, and tumor necosis factor (TNF)-α were determined by ELISA. RESULTS: Depending on the species super-family, the strains had different stimulation patterns. Except for both L. casei strains, the cell extract of bifidobacteriaand lactobacilli had less stimulating capacity than cell debris, whereas the cell extract of E. coli nissle had simi- lar stimulating properties to that of the cell debris of the strain and significantly more stimulating capacity than that of bifi dobacteria and lactobacilli. The cell debris of bifi dobacteria stimulated more cytokine release than the cell debris of lactobacilli. The cell debris of lactobacilli did not have a stimulating capacity when lower concentra- tions were used. Neither cell extraction nor cell debris had an inhibitory effect on the production of the tested cytokines by stimulated PBMNC. CONCLUSION: The incubation of probiotic strains, which have been used in clinical trials for inflammatory diseases, with immunocompetent cells leads to different species specifi c reactions. High IL-10 response to cell de- bris of bifi dobacteria and E. coli nissle can be found. This corresponds to positive effects of bifi dobacteria and E. coli nissle in clinical trials for inflammatory bowel disease compared to negative outcomes obtained with lactoba- cilli. | Ulf Helwig Karen M Lammers Fernando Rizzello Patricia Brigidi Verena Rohleder Elisabetta Caramelli Paolo Giochetti Juergen Schrezenmeir Ulrich R Foelsch Stefan Schreiber Massimo Campieri | 2006 | World Journal of Gastroenterology2006，12，37： | 3 |
| 7 | Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells显示文摘 | Patricia DA Lima Megan M Tu Mir Munir A Rahim Annie R Peng B Anne Croy Andrew P Makrigiannis | 2014 | Cellular & Molecular Immunology2014，11，5： | 3 |
| 8 | Effects of protein deprivation and re-feeding on P2X_2 receptors in enteric neurons显示文摘AIM:To investigate the effects of malnutrition and refeeding on the P2X2 receptor,nitric oxide synthase(NOS),calretinin,calbindin and choline acetyltransferase(ChAT) in neurons of the rat ileum.METHODS:We analyzed the co-localization,numbers and sizes of P2X2-expressing neurons in relation to NOS-immunoreactive(IR),calbindin-IR,ChAT-IR,and calretinin-IR neurons of the myenteric and submucosal plexus.The experimental groups consisted of:(1) rats maintained on normal feed throughout pregnancy until 42 d post-parturition(N);(2) rats deprived of protein throughout pregnancy and 42 d post-parturition(D);and(3) rats undernourished for 21 d post-parturition and then given a protein diet from days 22 to 42(DR).The myenteric and submucosal plexuses were evaluated by double labeling by immunohistochemical methods for P2X2 receptor,NOS,ChAT,calbindin and calretinin.RESULTS:We found similar P2X2 receptor immunoreactivity in the cytoplasm and surface membranes of myenteric and submucosal neurons from the N,D and DR groups.Double labeling of the myenteric plexus demonstrated that approximately 100% of NOS-IR,calbindin-IR,calretinin-IR and ChAT-IR neurons in all groups also expressed the P2X2 receptor.In the submucosal plexus,the calretinin-IR,ChAT-IR and calbindin-IR neurons were nearly all immunoreactive for the P2X2 receptor.In the myenteric plexus,there was a 19% increase in numbers per cm2 for P2X2 receptor-IR neurons,64% for NOS-IR,84% for calretinin-IR and 26% for ChAT-IR neurons in the D group.The spatial density of calbindin-IR neurons,however,did not differ among the three groups.The submucosal neuronal density increased for calbindin-IR,calretinin-IR and ChAT-IR neurons.The average size of neurons in the myenteric plexus neurons in the D group was less than that in the controls and,in the re-fed rats;there was a 34% reduction in size only for the calretinin-IR neurons.CONCLUSION:This work demonstrates that expression of the P2X2 receptor is present in inhibitory,intrinsic primary afferent,cholinergic secretomotor and vasomotor neurons.Undernutrition affected P2X2 receptor expression in the submucosal plexus,and neuronal and size.These changes were rescued in the re-fed rats. | Rúbia Misawa Priscila Azevedo Girotti Márcia Sanae Mizuno Edson Aparecido Liberti John Barton Furness Patricia Castelucci | 2010 | World Journal of Gastroenterology2010，16，29： | 2 |
| 9 | Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2R[gamma]c-deficient mice显示文摘 | Sarry Jean-Emmanuel Murphy Kathleen Perry Robin Sanchez Patricia V Secreto Anthony Keefer Cathy Swider Cezary R Strzelecki Anne-Claire Cavelier Cindy Récher Christian Mansat-De Mas Véronique Delabesse Eric Danet-Desnoyers G Carroll Martin | 2011 | Journal of Clinical Investigation2011，，1： | 2 |
| 10 | Effects of activated carbon surface chemistry and pore structure on the adsorption of organic contaminants from aqueous solution显示文摘 | Li Lei Patricia A Quinlivan Detlif R U Knappe | 2002 | Carbon2002，40，： | 1 |
| 11 | A functional polymorphism within plasminogen activator urokinase (PLAU) is associated with Alzheimer's disease显示文摘 | Matthias R Lidija K Patricia F | | 0，，： | 1 |
| 12 | Identification and characterization of pathogenic Aerornonas veronii biovar, sobria associated with epizootic ulcerative syndrome in fish in Bangladesh显示文摘 | MOKHLASUR R PATRICIA C INGER K | 2002 | Appl Environ Microbiol2002，68，2： | 1 |
| 13 | Apoptosis and thyroiditis 显示文摘 | Patricia L Arscott and James R Baker Jr | 1998 | Clinical immunology and immunopathology1998，87，3： | 1 |
| 14 | An overview of the functionality of expolysaccharides produced by lactic acid bacteria显示文摘 | PATRICIA R M JEROEN H PIETERNELA Z | 2002 | International Dairy Journal2002，12，： | 1 |
| 15 | Understanding the Influence of National Culture on the Development of Trust显示文摘 | PATRICIA M DONEY JOSEPH P CANNON MICHAEL R MULLEN | 1998 | The Academy of Management Review1998，23，3： | 1 |
| 16 | Changes in glutathione S-transferase activity in DDT resistant natural Mexican populations of Anopheles albimanus under different insecticide resistance management strategies显示文摘 | Patricia R P Américo D R Janet H | 2006 | Pesticide Biochemistry and Physiology2006，86，2： | 1 |
| 17 | CT-guided transthoracic needle aspiration biopsy of pulmonary nodules:needle size and pneumothorax rate显示文摘 | Patricia R Geraghty Stephen T | 2003 | Radiology2003，229，2： | 1 |
| 18 | Re- trieval-induced forgetting and executive control 显示文摘 | PATRICIA R M SORIANO F CARLOS J | 2009 | Psychological Science2009，20，9： | 1 |
| 19 | Effects of activated carbon characteristics on the simultaneous adsorption of aqueous organic micropollutants and natural organic matter 显示文摘 | Patricia A Q Li L Detlef R U | 2005 | Water Research2005，39，8： | 1 |
| 20 | Effects of activated carbon surface chemistry and pose structure on the adsorption of organic contaminants from aqueous solution显示文摘 | LI Lei PATRICIA A Q DETLEF R U K | 2002 | Carbon2002，40，12： | 1 |
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