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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 | Iron and non-alcoholic fatty liver disease显示文摘The mechanisms that promote liver injury in non-alcoholic fatty liver disease(NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis. | Laurence J Britton V Nathan Subramaniam Darrell HG Crawford | 2016 | World Journal of Gastroenterology2016，22，36： | 14 |
| 3 | PIV measurements of turbulent jets issuing from triangular and circular orifice plates显示文摘The present study experimentally investigated the near-field flow mixing characteristics of two turbulent jets issuing from equilateral triangular and circular orifice plates into effectively unbounded surroundings,respectively.Planar particle image velocimetry(PIV) was applied to measure the velocity field at the same Reynolds number of Re=50,000,where Re = UeDe /with Ue being the exit bulk velocity and the kinematic viscosity of fluid,D e the equivalent diameters.The instantaneous velocity,mean velocity,Reynolds stresses were obtained.From the mean velocity field,the centreline velocity decay rate and half-velocity width were derived.Comparing the mixing characteristics of the two jets,it is found that the triangular jet has a faster mixing rate than the circular counterpart.The triangular jet entrainments with the ambient fluid at a higher rate in the near field.This is evidenced by a shorter unmixed core,faster Reynolds stress and centreline turbulence intensity growth.The primary coherent structures in the near field are found to break down more rapidly in the triangular jet as compared to the circular jet.Over the entire measurement region,the triangular jet maintained a higher rate of decay and spread.Moreover,all components of Reynolds stress of the triangular jet appear to reach their peaks earlier,and then decay more rapidly than those of the circular jet.In addition,the axis-switching phenomenon is observed in the triangular jet. | XU MinYi ZHANG JianPeng MI JianChun NATHAN G J KALT P A M | 2013 | Science China(Physics,Mechanics & Astronomy)2013，56，6： | 7 |
| 4 | Arterial Resection During Pancreatectomy for Pancreatic Cancer: A Systematic Review and Meta-Analysis显示文摘 | Nathan Mollberg Nuh N. Rahbari Moritz Koch Werner Hartwig Yumiko Hoeger Markus W. Büchler Jürgen Weitz | 2011 | Annals of Surgery2011，，6： | 5 |
| 5 | 出口雷诺数对平面射流自保持性的影响显示文摘通过实验研究出口雷诺数对平面湍流射流自保持性的影响.测量的射流来自相同的喷嘴但不同的雷诺数Re(≡Ujh/ν,其中Uj是出口平均速度、h是窄缝出口的厚度和ν是黏性系数),其变化范围是Re=4582—57735.所得的数据包括沿轴线的平均速度、湍流强度、积分尺度、高阶矩和能谱.实验发现,随着Re的增大,平面射流发展减慢,平均速度和湍流强度更难达到自保持状态.沿轴线的积分尺度随轴向距离成线性增长但随雷诺数的增大增长速度减慢.同时发现,平面射流的局部雷诺数会随轴向距离的增大而增大.最后,通过对比湍流能谱并结合以往发表的结果,对不同雷诺数的射流所表现出的不同的统计学行为给出了解释. | 米建春 冯宝平 Deo Ravinesh C Nathan Graham J | 2009 | 物理学报2009，58，11： | 3 |
| 6 | Hepatocellular Carcinoma: Current Management and Perspectives for the Future显示文摘 | Nuh N. Rahbari Arianeb Mehrabi Nathan M. Mollberg Sascha A. Müller Moritz Koch Markus W. Büchler Jürgen Weitz | 2011 | Annals of Surgery2011，，3： | 3 |
| 7 | Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma显示文摘This report describes a patient that developed recurrent metastatic hepatocellular carcinoma(HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. | Michael L Caparelli Nathan J Roberts Timothy S Braverman Robert M Stevens Edward R Broun Shyam Allamaneni | 2016 | World Journal of Hepatology2016，8，23： | 2 |
| 8 | A randomised comparison of parecoxib versus placebo for pain management following minor day stay gynaecological surgery显示文摘 | Luscombe K S McDonnell N J Muchatuta N A Paech M J Nathan E A | 2010 | Anaesthesia and Intensive Care2010，，1： | 2 |
| 9 | Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development显示文摘 | Philippe J Guerin Piero Olliaro Francois Nosten Pierre Druilhe Ramanan Laxminarayan Fred Binka Wen L Kilama Nathan Ford Nicholas J White | 2002 | The Lancet Infectious Diseases2002，，9： | 2 |
| 10 | Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db / db Mice显示文摘 | Hong Chen Olga Charlat Louis A Tartaglia Elizabeth A Woolf Xun Weng Stephen J Ellis Nathan D Lakey Janice Culpepper Karen J More Roger E Breitbart Geoffrey M Duyk Robert I Tepper Jay P Morgenstern | 1996 | Cell1996，，3： | 2 |
| 11 | The effect of different initial conditions on the exit flow from a fluidic precessing jet nozzle显示文摘 | Wong C Y Nathan G J O' Doherty T | 2003 | Experiments in Fluids2003，36，： | 1 |
| 12 | Effect of fluids on coal permeability : Impact on horizontal wellbore stability显示文摘 | Thomas Gentzis Nathan Deisman Richard J | 2009 | lnternational Journal of Coal Geology2009，78，： | 1 |
| 13 | Management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy显示文摘 | Nathan D M Buse J B Davidson M B | 2008 | Diabetologia2008，16，51： | 1 |
| 14 | A study of the prevalence of sexually transmitted infections and related conditions in pregnant women attending a sexual health service显示文摘 | Bareny O J Nathan M | 2005 | Int J STD AIDS2005，16，5： | 1 |
| 15 | A Phase Ib trial of CA4P (combretastatin A-4 phosphate),carboplatin,and paclitaxel in patients with advanced cancer显示文摘 | Rustin G J Shreeves G Nathan P D | 2010 | Br J Cancer2010，102，9： | 1 |
| 16 | Effect of ac electrodeposition conditions on the growth of high aspect ratio copper nanowires in porous aluminum oxide templates 显示文摘 | NATHAN J K JOEL A H | 2005 | Journal of physical chemistry B2005，109，17： | 1 |
| 17 | Mixing characteristics of axisymmetric free jets from a contoured nozzle, an orifice plate and a pipe显示文摘 | Mi J Nathan G J Nobes D S | 2001 | Transactions of the ASME2001，123，： | 1 |
| 18 | Evaluation of automated techniques for base flow and recession analysis显示文摘 | Nathan R J McMahon T A | 1990 | Water Resources Research1990，26，7： | 1 |
| 19 | Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus显示文摘 | Nathan DM Lachin J Cleary P | 2003 | N Engl J Med2003，348，23： | 1 |
| 20 | The use of extracorpo- real membrane oxygenation, high-frequency oscillatory ventilation, and surfactant for the management of intraoperative acute pulmonary hemorrhage in tetralogy of fallot 显示文摘 | Nathan M Kalyanaraman M Blank J | 2011 | J Cardiothorac Vasc Anesth2011，25，2： | 1 |
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