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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

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中华肿瘤防治杂志 2021年第24期28卷 1841-1850页

作者：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 山东省肿瘤防治研究院(山东省肿瘤医院) 山东第一医科大学(山东省医学科学院)山东济南250117 不详 Department of Radiation Oncology The University of Texas M D Anderson Cancer CenterHoustonTX 77030USA

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,... 详细信息

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***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。

关键词：帕博利珠单抗非小细胞肺癌放疗汇总分析

A Pilot Study about the First Cases of Coronary Angioplasty in Democratic Republic of Congo/Kinshasa: Patient Profile

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Case Reports in Clinical Medicine 2023年第10期12卷 371-388页

作者： David Ipungu Gondele Eulethère Vita Kintoki Yves Lubenga Georges Ngoyi Trésor Mvunzi Dominique Mupepe nathan Buila Zéphirin Kamuanga Fahd Qureshi Aliosha Nkodila Jean Robert Rissasi Makulo Jean René M’buyamba-Kabangu Cardiology Unit University of Kinshasa Hospital Kinshasa The Democratic Republic of Congo Cardiology Unit Centre Hospitalier Victor Dupouy Argenteuil France Cardiology Unit H.J. Hospitals Kinshasa The Democratic Republic of Congo Public Health and Familly Medecine Protestant University of Congo Kinshasa The Democratic Republic of Congo Nephrology Unit University of Kinshasa Hospital Kinshasa The Democratic Republic of Congo

Background: The objective of this pilot study was to describe clinical profile, electric, echocardiographic and angiographic caracteristics with procedural outcome of congolease patients undergoing coronarography in the first and only one cardiac catheterization center opened in Kinshasa. Methods: An analytical cross-sectional study was carried out over a period from October 2019 (date of establishment of the first coronary angiography unit in DR Congo) to March 2021. we proceeded to a serial sampling of the consecutive cases of all the patients who have an angiographic exploration of coronary arteries. Clinical, ECG and cardiac ultrasound data were collected in all patients. The indications for the coronary angiography examination were set by differents cardiologists on the basis of repolarization troubles in the electrocardiogram, cinetic troubles in echocardiography, positive stress test and chest pain in patients with cardiovascular risq factors. Results: The serie (47 patients) was predominantly male with a sex ratio M/w of 2.6. The average age was 59.8 ± 10.5 years. Arterial hypertension (HBP) was the main risk factor (89.4%);followed by diabetes mellitus (14.9%). Chest pain was the main functional sign with an atypical character in 44.7%. The ECG showed ST segment depression (17%) and T wave inversion (17%), the anterior region being the most affected. Hypokinesia was the most common echocardiographic abnormality (34%), followed by akinesia (10.6%). The anteroseptal and apical territories were affected in 12.8%. Dilated myocardiopathy (DMC) was significantly predominant in the male sex (29.4% vs 7.7%;p = 0.011). with radial puncture as the main approach, coronary angiography was pathological in 44% revealing mono-truncal lesions. The left coronary network was the most affected: the middle inter ventricular artery (12.8%), the proximal interventricular artery (10.6%) and the proximal circonflex artery (10.6%). In multivariate logistic regression analysis, age

关键词： Heart Disease Coronary Angioplasty Patient Profile Pilot Study Democratic Republic of Congo

Twenty years of human immunodeficiency virus care at the Mayo Clinic:Past,present and future

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world Journal of Virology 2016年第2期5卷 63-67页

作者： nathan w Cummins Andrew D Badley Mary J Kasten Rahul Sampath Zelalem Temesgen Jennifer A whitaker John w wilson Joseph D Yao John Zeuli Stacey A Rizza Division of Infectious Diseases Mayo ClinicRochester

The Mayo human immunodeficiency virus(HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a "Mayo Model" of HIV care that exceeds national outcomes and may be applicable in other settings.

关键词： Human immunodeficiency virus/acquired immune deficiency syndrome Patient engagement Care Cascade Multidisciplinary care Minimally disruptive medicine

行体外循环冠状动脉搭桥术的低风险患者中早期神经认知功能缺陷的预测因素

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世界核心医学期刊文摘（心脏病学分册） 2007年第1期3卷 34-35页

作者： Boodhwani M. Rubens F.D. wozny D. H.J. nathan 刘少伟 H341 40 Ruskin Street Ottawa Ont. K1Y 4W7 CanadaDr

背景:即使是在心脏手术的低风险患者中,术后认知功能缺陷(POCD)也是病死原因之一,且经常发生。神经认知功能缺陷的预测因素可用于确定潜在的、可干预的危险因素,以及可能需要采取替代性血运重建策略的高风险患者。方法和结果:448例接受... 详细信息

背景:即使是在心脏手术的低风险患者中,术后认知功能缺陷(POCD)也是病死原因之一,且经常发生。神经认知功能缺陷的预测因素可用于确定潜在的、可干预的危险因素,以及可能需要采取替代性血运重建策略的高风险患者。方法和结果:448例接受冠状动脉手术[冠状动脉搭桥术(CABG)]的患者分别在术前和术后进行标准化神经认知功能测试,作为两项评估冠状动脉手术中适度低温后果的随机试验中的一部分。

关键词：冠状动脉搭桥术神经认知血运重建病死原因随机试验插管时间肌酐水平多变量重症监护停留时

Synthesis of Substituted Benzothiazepine Compounds with Medicinal Potential

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Notes,outline and divergence times of Basidiomycota

International Journal of Organic Chemistry（有机化学国际期刊） 2020年第3期

作者： Clare E. Gutteridge Brett w. Sadowski Stephen M. Hughes J. Alan Friedlander Leighton G. Rodrigo Michael C. Baxter nathan C. Lorei Jonathan E. Harrell Michael T. O’Neil2

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Fungal Diversity 2019年第6期99卷 105-367页

作者： Mao-Qiang He Rui-Lin Zhao Kevin D.Hyde Dominik Begerow Martin Kemler Andrey Yurkov Eric H.C.McKenzie Olivier Raspe Makoto Kakishima Santiago Sanchez-Ramırez Else C.Vellinga Roy Halling Viktor Papp Ivan V.Zmitrovich Bart Buyck Damien Ertz Nalin N.wijayawardene Bao-Kai Cui nathan Schoutteten Xin-Zhan Liu Tai-Hui Li Yi-Jian Yao Xin-Yu Zhu An-Qi Liu Guo-Jie Li Ming-Zhe Zhang Zhi-Lin Ling Bin Cao Vladimir Antonin Teun Boekhout Bianca Denise Barbosa da Silva Eske De Crop Cony Decock Balint Dima Arun Kumar Dutta Jack w.Fell Jozsef Geml Masoomeh Ghobad-Nejhad Admir J.Giachini Tatiana B.Gibertoni Sergio P.Gorjon Danny Haelewaters Shuang-Hui He Brendan P.Hodkinson Egon Horak Tamotsu Hoshino Alfredo Justo Young woon Lim Nelson Menolli Jr Armin Mesic Jean-Marc Moncalvo Gregory M.Mueller La szlo G.Nagy RHenrik Nilsson Machiel Noordeloos Jorinde Nuytinck Takamichi Orihara Cheewangkoon Ratchadawan Mario Rajchenberg Alexandre G.S.Silva-Filho Marcelo Aloisio Sulzbacher Zdenko Tkalcec Ricardo Valenzuela Annemieke Verbeken Alfredo Vizzini Felipe wartchow Tie-Zheng wei Michael weiB Chang-Lin Zhao Paul M.Kirk State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101People’s Republic of China Department of Entomology and Plant Pathology Faculty of AgricultureChiang Mai UniversityChiang Mai 50200Thailand Center of Excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand College of Life Sciences University of Chinese Academy of SciencesHuairou DistrictBeijing 100408People’s Republic of China Ruhr-Universitat Bochum AG GeobotanikND03UniversitatsstraBe 15044801 BochumGermany Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures InhoffenstraBe 7B38124 BrunswickGermany Manaaki whenua-Landcare Research Private Bag 92170AucklandNew Zealand Research Department Meise Botanic GardenNieuwelaan 381860 MeiseBelgium Service General de l'Enseignement superieur et de la Recherche scientifique Federation Wallonie-BruxellesLavallee 11080 BrusselsBelgium University of Tsukuba TsukubaIbaraki 305-8572Japan Department of Ecology and Evolutionary Biology University of Toronto25 Willcocks St.TorontoON M5S 3B2Canada Berkeley USA Institute of Systematic Botany The New York Botanical GardenBronxNY 10458-5126USA Department of Botany Szent Istvan University1518 BudapestHungary Komarov Botanical Institute Russian Academy of SciencesProfessor Popov st.2Saint PetersburgRussia 197376 Institut pour Systematique Ecologie Biodiversite(ISYEB UMR 7205) Sorbonne universiteMuseum National d’Histoire Naturelle CP 39CNRSDepartement Origines et Evolution12 Rue Buffon75005 ParisFrance Institute of Microbiology Beijing Forestry UniversityBeijing 100083People’s Republic of China Department of Biology Research Group MycologyGhent UniversityK.L.Ledeganckstraat 359000 GhentBelgium State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Institute of MicrobiologyGuangzhou 510070People’s Republic of China Department of Botany Moravian Mu

The Basidiomycota constitutes a major phylum of the kingdom Fungi and is second in species numbers to the *** present work provides an overview of all validly published,currently used basidiomycete genera to date in a single *** outline of all genera of Basidiomycota is provided,which includes 1928 currently used genera names,with 1263 synonyms,which are distributed in 241 families,68 orders,18 classes and four *** provide brief notes for each accepted genus including information on classification,number of accepted species,type species,life mode,habitat,distribution,and sequence ***,three phylogenetic analyses with combined LSU,SSU,5.8s,rpb1,rpb2,and ef1 datasets for the subphyla Agaricomycotina,Pucciniomycotina and Ustilaginomycotina are conducted,*** time estimates are provided to the family level with 632 species from 62 orders,168 families and 605 *** study indicates that the divergence times of the subphyla in Basidiomycota are 406-430 Mya,classes are 211-383 Mya,and orders are 99-323 Mya,which are largely consistent with previous *** this study,all phylogenetically supported families were dated,with the families of Agaricomycotina diverging from 27-178 Mya,Pucciniomycotina from 85-222 Mya,and Ustilaginomycotina from 79-177 *** times as additional criterion in ranking provide additional evidence to resolve taxonomic problems in the Basidiomycota taxonomic system,and also provide a better understanding of their phylogeny and evolution.

关键词： Classification Molecular clock Fungi Systematics Taxonomy

Effect of Graphene Nanoplatelets Presence on the Thermal and Mechanical Properties of Polypropylene Fibers Produced by Melt Spinning

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材料科学与工程（中英文B版） 2020年第2期10卷 53-63页

作者： Ricardo Rodrigo Ramos Cecci Adriano Alves Passos nathan Riany Valério Albino Daniel da Silva Vicente Ademir Severino Duarte Maria Inês Bruno Tavares Instituto de Macromoléculas Professora Eloísa Mano Universidade Federal do Rio de JaneiroRio de Janeiro 21941-598Brazil SENAI Innovation Institute for Biosynthetic and Fibers SENAI CETIQTRio de Janeiro 20961-020Brazil

In aiming to obtain fibers with enhanced thermal and mechanical properties,graphene based textile fibers with 144 filaments were developed using an approach in which the PP/GnP(polypropylene/graphene nanoplatelets)nanocomposite was employed as conductive material in a fiber with circular cross-section *** kinetics of thermal degradation was evaluated by the Broido method using thermogravimetric analysis(TGA).Activation energy was enhanced from 260.6 kJ·mol^-1 to 337.4 kJ·mol^-1 compared to the neat *** increased the thermal stability of the PP,slowing its degradation by thermal ***,the degree of crystallization declined as the GnP content increased,reducing the tenacity of the yarn,but improving its elastic modulus from 91.9 to 95.9 cN/tex,being a promising alternative to produce smart *** conclusion,it has been confirmed that GnP loading up to 1%(w/w)can be incorporated into polypropylene by melt spinning and that the resulting nanocomposite fibers are suitable for several applications in the textile industry.

关键词： Polymer fibers polypropylene graphene nanoplatelets degradation kinetics

LFA-1 antagonist (BIRT377) similarly reverses peripheral neuropathic pain in male and female mice with underlying sex divergent peripheral immune proinflammatory phenotypes

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Neuroimmunology and Neuroinflammation 2019年第7期6卷 12-43页

作者： Shahani Noor Melody S.Sun Arden G.Vanderwall Mara A.Havard Jacob E.Sanchez nathan w.Harris Monique V.Nysus Jeffrey P.Norenberg Harrison T.west Carsten R.wagner Lauren L.Jantzie Nikolaos Mellios Erin D.Milligan Department of Neurosciences School of MedicineUniversity of New MexicoAlbuquerqueNM 87131USA Department of Anesthesiology and Critical Care University of New MexicoAlbuquerqueNM 87131USA Department of Pediatrics and Neurology Johns Hopkins University School of MedicineBaltimoreMD 21205-2196USA Department of Radiopharmaceutical Sciences College of PharmacyNew Mexico Center for Isotopes in MedicineUniversity of New MexicoAlbuquerqueNM 87131USA Department of Medicinal Chemistry University of MinnesotaCollege of PharmacyMinneapolisMN 55455USA

Aim:The majority of preclinical studies investigating aberrant glial-neuroimmune actions underlying neuropathic pain have focused on male rodent ***,studies have shown peripheral immune cells play a more prominent role than glial cells in mediating pathological pain in ***,we compared the onset and duration of allodynia in males and females,and the anti-allodynic action of a potentially novel therapeutic drug(BIRT377)that not only antagonizes the action of lymphocyte function-associated antigen-1(LFA-1)to reduce cell migration in the periphery,but may also directly alter the cellular inflammatory ***:Male and female mice were subjected to peripheral nerve injury chronic constriction injury(CCI)applying two methods,using either 4-0 or 5-0 chromic gut suture material,to examine potential sex differences in the onset,magnitude and duration of *** sensitivity before and after CCI and application of intravenous BIRT377 was *** and spinal tissues were analyzed for protein(multiplex electrochemiluminescence technology)and mRNA expression(quantitative real-time PCR).The phenotype of peripheral T cells was determined using flow ***:Sex differences in proinflammatory CCL2 and IL-1βand the anti-inflammatory IL-10 were observed from a set of cytokines analyzed.A profound proinflammatory T cell(Th17)response in the periphery and spinal cord was also observed in neuropathic ***377 reversed pain,reduced IL-1βand TNF,and increased IL-10 and transforming growth factor(TGF)-β1,also an anti-inflammatory cytokine,in both ***,female-derived T cell cytokines are transcriptionally regulated by BIRT377,as demonstrated by reducing proinflammatory IL-17A production with concurrent increases in IL-10,TGF-β1 and the anti-inflammatory regulatory T cell-related factor,***:This study supports that divergent peripheral immune and neuroimmune responses during neuropathy exists between males and

关键词： Neuropathic pain glia neuroimmune peripheral immune T cells

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啤酒面糊煎炸更美味

环球科学 2011年第3期 11-11页

作者： w．韦特·吉布斯（w．wart Gibbs）内森·米尔沃尔德（nathan Myhrvold）王栋（译）

你走进酒吧点了一份美味的炸鱼薯条餐，如果发现鱼肉嫩多汁，皮超级酥脆，那么，这道炸鱼所用的包裹面糊，很可能是厨师主要用啤酒来凋配的。啤酒是煎炸用裹面糊的绝好原料，

关键词：啤酒美味炸鱼薯条鱼肉厨师