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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使用cDNA微阵列和组织微阵列对三种上皮性卵巢肿瘤基因表达的分析显示文摘背景与目的卵巢癌是在妇科恶性肿瘤中死亡率最高的肿瘤,主要原因是由于缺乏有效的早期诊断方法。为了发现新的、特异性癌基因和进一步探索上皮性卵巢癌的临床意义,本文探索出一种新方法,通过结合cDNA微阵列和RNA原位杂交冰冻组织微阵列的方法寻找特异性卵巢癌基因。方法利用cDNA微阵列筛选在3种不同卵巢癌中(卵巢浆液性交界性肿瘤、卵巢浆液性腺癌和卵巢子宫内膜样腺癌)显示有意义表达的基因,并由RNA原位杂交冰冻组织微阵列证实其结果。结果40个基因和ESTs显示出在卵巢浆液性交界性肿瘤、浆液性和子宫内膜样卵巢癌3种类型之间基因表达有明显的差异;EPHB6、PTPRF、GFER、ERG25、PLRP1,FLJ22060和WISP2被进一步用于RNA原位杂交冰冻组织微阵列研究,其结果与cDNA微阵列研究结果相符合。结论cDNA微阵列和RNA原位杂交冰冻组织微阵列相结合是一种理想的寻找癌相关基因的方法,EPHB6,PTPRF,GFER,ERG25,PLRP1,FLJ22060和WISP2有可能成为新的上皮性卵巢癌候选基因。郑敏 Simon R Kononen J Sauter G Mihatsch MJ Moch H 2004癌症2004,23,7:8
3麝香保心丸对血管平滑肌细胞表型转化的影响显示文摘目的:观察麝香保心丸(SXBXW)对血管平滑肌细胞表型转化的影响。方法:以血管平滑肌细胞系RASMCP8为模型,设对照组,SXBXW0.25、0.5、1.0和2.0g/L组,经不同浓度的SXBXW作用后,用流式细胞术测定RASMCP8细胞的收缩型特异性分子标志物α-平滑肌肌动蛋白(α-SMA)和平滑肌肌球蛋白重链(SM-MHC)表达的变化。结果:与对照组相比,经SXBXW处理后,α-SMA和SM-MHC的阴性细胞百分比降低,阳性细胞百分比增加。结论:SXBXW能促使血管平滑肌细胞的表型从合成型向收缩型转化。车贤达 Simon X Liang Xingmai Jiang 高瑞兰 张庆刚 钱琳艳 赵嫣 Beng H Chong 2010中国病理生理杂志2010,26,11:6
4麝香保心丸对血管平滑肌细胞表型转化和增殖的影响显示文摘目的:观察麝香保心丸(SXBXW)对血管平滑肌细胞表型转化和增殖的影响。方法:培养平滑肌细胞系RASMC P8细胞并将其分成对照组和SXBXW药物组。并观察SXBXW对细胞增殖、增殖周期、对血管平滑肌α-平滑肌肌动蛋白(α-SMA)和肌球蛋白重链(SM-MHC)表达的影响。结果:麝香保心丸抑制RASMC P8细胞由收缩型向合成型转化,表现为收缩型细胞的标志物α-SMA和SM-MHC标记的阳性细胞增加,阴性细胞减少,同时抑制RASMC P8细胞周期从G1期向S期转化,从而抑制细胞的增殖。结论:SXBXW能有效的抑制血管平滑肌的细胞表型转化和细胞增殖。张庆刚 高瑞兰 Beng H Chong Simon X Liang Xingmai Jiang 车贤达 2014中华中医药学刊2014,32,4:5
5Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study显示文摘Laurent Beaugerie Nicole Brousse Anne Marie Bouvier Jean Frédéric Colombel Marc Lémann Jacques Cosnes Xavier Hébuterne Antoine Cortot Yoram Bouhnik Jean Pierre Gendre Tabassome Simon Marc Maynadié Olivier Hermine Jean Faivre Fabrice Carrat 2009The Lancet . 2009 (9701)2009,,:4
6Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion显示文摘Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal 2017World Journal of Gastroenterology2017,23,48:4
7Second European evidence-based consensus on the diagnosis and management of ulcerative colitis: Special situations显示文摘Gert Van Assche Axel Dignass Bernd Bokemeyer Silvio Danese Paolo Gionchetti Gabriele Moser Laurent Beaugerie Fernando Gomollón Winfried H?user Klaus Herrlinger Bas Oldenburg Julian Panes Francisco Portela Gerhard Rogler Jürgen Stein Herbert Tilg Simon Tra 2012Journal of Crohn’s and Colitis2012,,:4
8光动力疗法治疗非小细胞肺癌显示文摘光动力疗法被越来越多地应用于治疗胸部恶性肿瘤。对于早期非小细胞肺癌(如支气管腔内肺癌)、X线检查阴性或同时性原发癌,光动疗法可作为主要治疗手段进行腔内根治性治疗。作为单一根治疗法,光动力疗法是治疗支气管镜可见≤1 cm且无软骨外浸润的肺部肿瘤的最有效方法。对于晚期非小细胞癌患者,光动力治疗可以作为综合根治疗法的一部分,用于减轻阻塞性支气管内病变,增加可手术性或缩小所需手术范围。本文对现有发表的应用光动力疗法治疗至少10例以上非小细胞肺癌病例的研究文献进行综述,提出了光动力疗法应用的治疗建议并进行了总结。Charles B Simone II Joseph S Friedberg Eli Glatstein James P Stevenson Daniel H Sterman Stephen M Hahn Keith A Cengel 袁光金 李金銮 朱宇熹 凌扬 2013国际病理科学与临床杂志2013,33,3:3
9Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study显示文摘BACKGROUND Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut–brain axis.AIM To facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field.METHODS The data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. VOSviewer software was used for data visualization.RESULTS A total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS(r = 0.951, P < 0.001). The United States was the most prolific country with 449(24%) publications, followed by the United Kingdom(n = 176, 9.4%), China(n = 154, 8.2%), and Italy(n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters:(1) The gut–brain axis related to IBS;(2) Clinical trials related to IBS and the microbiome;(3) Drugmediated manipulation of the gut microbiome;and(4) The role of the altered composition of intestinal microbiota in IBS prevention.CONCLUSION This is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.Sa'ed H Zyoud Simon Smale W Stephen Waring Waleed Sweileh Samah W Al-Jabi 2021World Journal of Gastroenterology2021,27,13:2
10Roles of Financial Innovation and Information Technology:Lessons from US Sub-prime Mortgage Crisis and Its Implications for China显示文摘The mortgage loan has evolved from a local lending instrument into a major global security and its role is unparallel to other financial instruments in the process of financial globalization.This paper explains how technology and financial innovation transformed the mortgage loan from a local security into a premier global security traded worldwide.It examines the fundamental flaws of this process and why it does not work in regards to mortgage lending and the re-securitization products that were created through financial innovation.The findings show that regulation was unable to keep pace with financial innovation,which created an environment where actors in the financial service sector were able to behave geographically irresponsibly by using information asymmetries to their advantage by participating in moral hazard activities and engaging in other immoral and unethical business practices that were centered around localized geography,which ultimately contributed to the global financial crisis.It also examines the roll of financial innovation in regard to the Lehman Brothers Mini-Bond in Hong and its role as a driving force behind China's newly emerging shadow banking sector.It concludes with a policy recommendation and its implication for China's continued economic development.James H LENZER JR Simon Xiaobin ZHAO 2012Chinese Geographical Science2012,22,3:2
11Quantitative Gas-Chromatographic Determination of Pentaerythritol and its By-Products by Direct Oximation and then Silyation of Aqueous Solutions显示文摘Simon C D Comninos H Cornish L 1993Journal of Chromatographic Science1993,31,6:2
12Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis显示文摘Neel R Gandhi Paul Nunn Keertan Dheda H Simon Schaaf Matteo Zignol Dick van Soolingen Paul Jensen Jaime Bayona 2010The Lancet2010,,9728:2
13Impact of machine perfusion of the liver on post-transplant biliary complications: A systematic review显示文摘AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBL). METHODS This systematic review was performed in accordance with the Preferred Reporting Systematic Reviews and MetaAnalysis(PRISMA) protocol. The following databases were searched: PubMed, MEDLINE and Scopus. The keyword 'liver transplantation' was used in combination with the free term 'machine perfusion'. Clinical studies reporting results of transplantation of donor human livers following ex situ or in situ MP were analysed. Details relating to donor characteristics, recipients, technique of MP performed and post-operative biliary complications(ITBL, bile leak and anastomotic strictures) were critically analysed.RESULTS Fifteen articles were considered to fit the criteria for this review. Ex situ normothermic MP was used in 6 studies, ex situ hypothermic MP in 5 studies and the other 4 studies investigated in situ normothermic regional perfusion(NRP) and controlled oxygenated rewarming. MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury: Such as hypothermic MP and NRP, have also reported lower rates of ITBL. Other biliary complications, such as biliary leak and anastomotic biliary strictures, are reported with similar incidences with all MP techniques. There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation. On the other hand, restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation, although universally accepted criteria have yet to be validated.CONCLUSION MP of the liver has the potential to have a positive impact on post-transplant biliary complications, specifically ITBL, and expand extended criteria donor livers utilisation.Yuri L Boteon Amanda PCS Boteon Joseph Attard Lorraine Wallace Ricky H Bhogal Simon C Afford 2018World Journal of Transplantation2018,8,6:2
14Celiac disease:Management of persistent symptoms in patients on a gluten-free diet显示文摘AIM:To investigate all patients referred to our center with non-responsive celiac disease (NRCD),to establish a cause for their continued symptoms.METHODS:We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period.These individuals were investigated to establish the eitiology of their continued symptoms.The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement.They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion.A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible.Colonoscopy,lactulose hydrogen breath testing,pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted.Their clinical progress was followed over a minimum of 2 years.RESULTS:One hundred and twelve consecutive patients were referred with NRCD.Twelve were found not to have celiac disease (CD).Of the remaining 100 patients,45% were not adequately adhering to a strict gluten-free diet,with 24 (53%) found to be inadvertently ingesting gluten,and 21 (47%) admitting noncompliance.Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%.Refractory CD was diagnosed in 9%.Three of these were diagnosed with intestinal lymphoma.After 2 years,78 patients remained well,eight had continuing symptoms,and four had died.CONCLUSION:In individuals with NRCD,a remediable cause can be found in 90%:with continued gluten ingestion as the leading cause.We propose an algorithm for investigation.David H Dewar Suzanne C Donnelly Simon D McLaughlin Matthew W Johnson H Julia Ellis Paul J Ciclitira 2012World Journal of Gastroenterology2012,18,12:2
15MMP/ TIMP expression in sponlaneously hypertensive heart failure rats: the effect of ACE - and MMP - inhibition 显示文摘Li H Simon H Bocn TM etal 2000Cardiovasc Res2000,46,2:1
16Partitioning sparse matrices with eigenvectors of graphs显示文摘Pothen A Simon H D Liou K P 1990SIAM Journal on Matrix Analysis and Applications1990,11,3:1
17Longterm multiple color imaging of live cells using quantum dot bioconjugates 显示文摘Jaiswal J K Mattoussi H Mauro J M Simon S F 2003Nature Biotechnolgy2003,21,:1
18Architecture of Complexity显示文摘Simon H A 1962Proceedings of the American Philosophical Society1962,,:1
19Emotion processing in three systems:The medium and the message显示文摘SIMONS R DETENBER B H ROEDEMA T M 1999Psychophysiology1999,36,5:1
20Porous Cobalt(II)-organic frameworks with corrugated walls:structurally robust gas-sorption materials显示文摘Simon M H Chang J S Sung H J 2007An-gew Chem Int Ed2007,46,12:1
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