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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 | Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a^(-/-) mice显示文摘AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P < 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P < 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P < 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a-/- mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a-/- mice. | Kelley MK Haarberg Meghan J Wymore Brand Anne-Marie C Overstreet Catherine C Hauck Patricia A Murphy Jesse M Hostetter Amanda E Ramer-Tait Michael J Wannemuehler | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 8 |
| 3 | Lack of microRNA‐101 causes E‐cadherin functional deregulation through EZH2 up‐regulation in intestinal gastric cancer显示文摘 | Joana Carvalho Nicole C van Grieken Patricia M Pereira Sónia Sousa Marianne Tijssen Tineke E Buffart Bego?a Diosdado Heike Grabsch Manuel AS Santos Gerrit Meijer Raquel Seruca Beatriz Carvalho Carla Oliveira | 2012 | J Pathol2012，，1： | 3 |
| 4 | Bacterial microcosms obey Taylor’s law:effects of abiotic and biotic stress and genetics on mean and variance of population density显示文摘Introduction:According to the empirical regularity called Taylor’s law,the variance of population density in samples of populations is a power of the mean population density.The exponent is often between 1 and 2.Our experiments investigated how genetics,evolution,and environment shape Taylor’s law.Methods:Genetically different strains(wild type and hypermutator)of the bacterium Pseudomonas fluorescens evolved and were assayed under different environmental conditions(with and without antibiotic rifampicin and bacteriophage SBW252,separately and in combination).Results:Experimental treatments altered the exponent b,but not the power law form,of the relation between variance and mean population density.Bacterial populations treated only with rifampicin had a narrow range of mean population densities and exponent b=5.43.Populations exposed to rifampicin plus phage had b=1.51.In ancestral,control,and phage-exposed populations,mean abundance varied widely and b was not significantly different from 2.Evolutionary factors(mutation rate,selection)and ecological factors(abiotic,biotic)jointly influenced b.Conclusions:Taylor’s power law relationship accurately and robustly described variance as a function of mean population density,with overall exponent b=1.89.These and other experiments with different factors acting on bacterial population size support the relevance of models that predict‘universal’patterns of fluctuation scaling. | Oliver Kaltz Patricia Escobar-Páramo Michael E Hochberg Joel E Cohen | 2012 | Ecological Processes2012，1，1： | 3 |
| 5 | Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal显示文摘 | Suresh Vedantham Patricia E. Thorpe John F. Cardella Clement J. Grassi Nilesh H. Patel Hector Ferral Lawrence V. Hofmann Bertrand M. Janne d’Othée Vittorio P. Antonaci Elias N. Brountzos Daniel B. Brown Louis G. Martin Alan H. Matsumoto Steven G. Meranze | 2006 | Journal of Vascular and Interventional Radiology2006，，3： | 3 |
| 6 | Efficiency gains from regionalization: economic development in China revisited显示文摘 | Patricia E Byrnes James E Storbeck | 2000 | Socio-Economic Planning Sciences2000，，2： | 2 |
| 7 | Comparison of Topical Cyclosporine, Punctal Occlusion, and a Combination for the Treatment of Dry Eye显示文摘 | Calvin W Roberts Patricia E Carniglia Brian G Brazzo | 2007 | Cornea2007，，7： | 2 |
| 8 | HACCP development and regulatory assessment in the United States of America显示文摘 | John Kvenberg Patricia Stolfa Dorothy Stringfellow E Spencer Garrett | 2000 | Food Control2000，，5： | 2 |
| 9 | Continuous aspiration of subglottic secretions in the prevention of ventilator- associated pneumonia in the postoperative period of major heart surgery 显示文摘 | Bouza E Jesu is M PerezRN Patricia Munoz | 2008 | Chest2008，134，5： | 1 |
| 10 | Casts of Aporrectodea caliginosa (Savigny) and Lumbricus rubellus (Hoffmeister) differ in microbial activity,nutrient availability and aggregate stability显示文摘 | Richard J H Patricia M F Jacqueline E P | 2003 | Pedobiologia2003，47，： | 1 |
| 11 | Effect of Mortar Fineness and Adhesive Agents on Pullout Response of Steel Fibers显示文摘 | Guerrero Patricia Namiaan Antoine E | 2000 | ACI Materials Journal2000，97，1： | 1 |
| 12 | Percutaneous transthoracic needle aspiration biopsy显示文摘 | RYAN C LARSCHEID PATRICIA E THORPE WALTER J SCOTT | 1998 | Chest1998，114，： | 1 |
| 13 | Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)Reduces Food Intake in Mice 显示文摘 | Morley J E Michael H Patricia M | 1992 | Peptides1992，13，： | 1 |
| 14 | Population growth in U.S. counties, 1840–1990显示文摘 | Patricia E Beeson David N DeJong Werner Troesken | 2001 | Regional Science and Urban Economics2001，，6： | 1 |
| 15 | Reporting Standards for Endovascular Treatment of Lower Extremity Deep Vein Thrombosis显示文摘 | Suresh Vedantham Clement J. Grassi Hector Ferral Nilesh H. Patel Patricia E. Thorpe Vittorio P. Antonacci Bertrand M. Janne d’Othée Lawrence V. Hofmann John F. Cardella Sanjoy Kundu Curtis A. Lewis Marc S. Schwartzberg Robert J. Min David Sacks | 2009 | Journal of Vascular and Interventional Radiology2009，，7： | 1 |
| 16 | CHRONIC HEPATITIS C: HEPATIC IRON CONTENT DOES NOT CORRELATE WITH RESPONSE TO ANTIVIRAL THERAPY显示文摘 | Pereira Patricia da Silva Fucuta Silva Ivonete Sandra de Souza E Uehara Silvia Naomi de Oliveira Emori Christini Takemi Lanzoni Valéria Pereira Silva Antonio Eduardo Benedito Ferraz Maria Lucia Gomes | 2009 | Revista do Instituto de Medicina Tropical de S茫o Paulo2009，，6： | 1 |
| 17 | Cultural competence in mental health care: A review of model evaluations显示文摘 | Kamaldeep B Nasir W Patricia E | 2007 | BMC Health Service Research2007，7，： | 1 |
| 18 | A com- parison of surface water natural organic matter in raw filtered wa- ter samples, XAD, and reverse osmosis isolates 显示文摘 | PATRICIA A M M1VHAEL J P STEPHEN E C | 2002 | Water Re- search2002，36，： | 1 |
| 19 | Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal显示文摘 | Suresh Vedantham Patricia E. Thorpe John F. Cardella Clement J. Grassi Nilesh H. Patel Hector Ferral Lawrence V. Hofmann Bertrand M. Janne d’Othée Vittorio P. Antonaci Elias N. Brountzos Daniel B. Brown Louis G. Martin Alan H. Matsumoto Steven G. Meranze | 2009 | Journal of Vascular and Interventional Radiology2009，，7： | 1 |
| 20 | The Role of Sense of School Belonging and Gender in the Academic Adjustment of Latino Adolescents显示文摘 | Bernadeue S Yar C Patricia E | 2005 | Journal of Youth and Adolescence2005，34，6： | 1 |
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