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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 | 诊断性试验和策略的证据质量和推荐强度的分级显示文摘GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局, | Holger J Schünemann Andrew D Oxman Jan Brozek Paul Glasziou Roman Jaeschke Gunn E Vist John W Williams Jr Regina Kunz Jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓 黄程 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，5： | 7 |
| 3 | Hematological disorders and pulmonary hypertension显示文摘Pulmonary hypertension(PH),a serious disorder with a high morbidity and mortality rate,is known to occur in a number of unrelated systemic diseases.Several hematological disorders such as sickle cell disease,thalassemia and myeloproliferative diseases develop PH which worsens the prognosis.Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction.Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity,activation of proliferative and antiapoptotic pathways leading to vascular remodeling,elevated pulmonary artery pressure,right ventricular hypertrophy and premature death.Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide(NO),limiting its bioavailability,and leading to endothelial dysfunction.In addition,hemolysis releases arginase into the circulation which converts L-arginine to ornithine,thus bypassing NO production.Furthermore,treatments for hematological disorders such as immunosuppressive therapy,splenectomy,bone marrow transplantation,and radiation have been shown to contribute to the development of PH.Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension(PAH).Several studies have reported low iron levels in patients with idiopathic PAH,and iron deficiency is an important risk factor.This article reviews PH associated with hematological disorders and its mechanism:and iron homeostasis and its relevance to PH. | Rajamma Mathew Jing Huang Joseph M Wu John T Fallon Michael H Gewitz | 2016 | World Journal of Cardiology2016，8，12： | 6 |
| 4 | Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis显示文摘 | Andrés Cárdenas Pere Ginès Paul Marotta Frank Czerwiec John Oyuang Mónica Guevara Nezam H Afdhal | 2011 | Journal of Hepatology2011，，3： | 6 |
| 5 | Histone modifications:Targeting head and neck cancer stem cells显示文摘Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer worldwide, and is responsible for a quarter of a million deaths annually. The survival rate for HNSCC patients is poor, showing only minor improvement in the last three decades. Despite new surgical techniques and chemotherapy protocols, tumor resistance to chemotherapy remains a significant challenge for HNSCC patients. Numerous mechanisms underlie chemoresistance, including genetic and epigenetic alterations in cancer cells that may be acquired during treatment and activation of mitogenic signaling pathways, such as nuclear factor kappa-light-chain-enhancer-of activated B cell, that cause reduced apoptosis. In addition to dysfunctional molecular signaling, emerging evidence reveals involvement of cancer stem cells(CSCs) in tumor development and in tumor resistance to chemotherapy and radiotherapy. These observations have sparked interest in understanding the mechanisms involved in the control of CSC function and fate. Post-translational modifications of histones dynamically influence gene expression independent of alterations to the DNA sequence. Recent findings from our group have shown that pharmacological induction of posttranslational modifications of tumor histones dynamically modulates CSC plasticity. These findings suggest that a better understanding of the biology of CSCs in response to epigenetic switches and pharmacological inhibitors of histone function may directly translate to the development of a mechanism-based strategy to disrupt CSCs. In this review, we present and discuss current knowledge on epigenetic modifications of HNSCC and CSC response to DNA methylation and histone modifications. In addition, we discuss chromatin modifications and their role in tumor resistance to therapy. | John M Le Cristiane H Squarize Rogerio M Castilho | 2014 | World Journal of Stem Cells2014，6，5： | 6 |
| 6 | Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis显示文摘 | Katrin M Sjoquist Bryan H Burmeister B Mark Smithers John R Zalcberg R John Simes Andrew Barbour Val Gebski | 2011 | Lancet Oncology2011，，7： | 4 |
| 7 | ACC/AHA guidelines for the management of patients with unstable angina and non–st-segment elevation myocardial infarction显示文摘 | Eugene Braunwald Elliott M Antman John W Beasley Robert M Califf Melvin D Cheitlin Judith S Hochman Robert H Jones Dean Kereiakes Joel Kupersmith Thomas N Levin Carl J Pepine John W Schaeffer Earl E Smith David E Steward Pierre Theroux Raymond J Gibbons J | 2000 | Journal of the American College of Cardiology2000，，3： | 4 |
| 8 | Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer显示文摘 | Douglas K Rex John H Bond Sidney Winawer Theodore R Levin Randall W Burt David A Johnson Lynne M Kirk Scott Litlin David A Lieberman Jerome D Waye James Church John B Marshall Robert H Riddell | 2002 | The American Journal of Gastroenterology2002，，6： | 3 |
| 9 | Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial显示文摘 | Paul Y Kwo Eric J Lawitz Jonathan McCone Eugene R Schiff John M Vierling David Pound Mitchell N Davis Joseph S Galati Stuart C Gordon Natarajan Ravendhran Lorenzo Rossaro Frank H Anderson Ira M Jacobson Raymond Rubin Kenneth Koury Lisa D Pedicone Clifford | 2010 | The Lancet2010，，9742： | 3 |
| 10 | Cytoplasmic expression of p27^(kip1) is associated with a favourable prognosis in colorectal cancer patients显示文摘AIM: To evaluate the prognostic significance of p27kip1 in colorectal cancer patients. METHODS: Cytoplasmic and nuclear p27kip1 expression was evaluated in 418 colorectal cancers using tissue microarrays. Data were associated with known patient and tumor variables and long-term patient outcomes, providing further insight into the mechanisms by which p27kip1 may influence tumor development. RESULTS: Nuclear and cytoplasmic p27Kip1 expressions were detected in 59% and 19% of tumors respectively. Cytoplasmic p27Kip1 was almost invariably associated with positive nuclear p27Kip1 expression. Neither case correlat- ed with known clinical or pathological variables, includ- ing tumor stage, grade or extramural vascular invasion. Furthermore, nuclear p27kip1 expression had no impact on survival. However, we identified a significant correla- tion between expression of cytoplasmic p27kip1 and longer disease-specific survival times. On multivariate analysis, TNM stage and extramural vascular invasion were highly significant independent prognostic factors, with positive cytoplasmic p27 expression showing a trend towards im- proved patient survival (P = 0.059).CONCLUSION: These findings support the recent evi- dence that cytoplasmic p27kip1 has a distinct and impor- tant biological role that can influence tumor outcome. | Nicholas FS Watson Lindy G Durrant John H Scholefield Zahra Madjd Duncan Scrimgeour Ian Spendlove Ian O Ellis Poulam M Patel | 2006 | World Journal of Gastroenterology2006，12，39： | 3 |
| 11 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 12 | Prognostic impact of the Bismuth-Corlette classification:Higher rates of local unresectability in stageⅢb hilar cholangiocarcinoma显示文摘Background:The Bismuth-Corlette(BC)classification is used to categorize hilar cholangiocarcinoma by proximal extension along the biliary tree.As the right hepatic artery crosses just behind the left bile duct,we hypothesized that BCⅢb tumors would have a higher likelihood of local unresectability due to involvement of the contralateral artery.Methods:A retrospective review of a prospectively maintained database identified patients with hilar cholangiocarcinoma taken to the operating room for intended curative resection between April 2008 and September 2016.Cases were assigned BC stages based on preoperative imaging.Results:Sixty-eight patients were included in the study.All underwent staging laparoscopy after which 16 cases were aborted for metastatic disease.Of the remaining 52 cases,14 cases were explored and aborted for locally advanced disease.Thirty-eight underwent attempt at curative resection.After exclud-ing cases aborted for metastatic disease,the chance of proceeding with resection was 55.6%for BCⅢb staged lesions compared to 80.0%of BCⅢa lesions and to 82.4%for BCⅠ-Ⅲa staged lesions(P<0.05).About 44.4%of BCⅢb lesions were aborted for locally advanced disease versus 17.6%of remaining BC stages.Conclusions:When hilar cholangiocarcinoma is preoperatively staged as BCⅢb,surgeons should antici-pate higher rates of locally unresectable disease,likely involving the right hepatic artery. | Michael J Passeri Maria R Baimas-George Jesse K Sulzer David A Iannitti John B Martinie Erin H Baker Lee M Ocuin Dionisios Vrochides | 2020 | Hepatobiliary & Pancreatic Diseases International2020，19，2： | 3 |
| 13 | 澳大利亚初级保健诊所新发腰背痛患者的预后:起始队列研究显示文摘目的估计初级保健诊所内新发腰背痛患者的1年预后,并确定其预后因素。设计1年随访队列研究。地点澳大利亚悉尼的初级保健诊所。参试者初级保健诊所接诊的973例非特异性腰背痛连续患者(平均年龄43.3岁,男性54.8%)。该起始队列患者腰背痛时间不足两周,征集自170名全科医生、理疗师或按摩师诊所。主要评估指标参试者完成基线调查问卷后,分别于初次就诊后6周、3个月和21个月时复查评估。评估内容包括:工作恢复情况、功能恢复情况和疼痛消失情况。潜在预后因素与恢复所需时间的关联性用Cox回归建模分析。结果12个月随访率〉97%。基线时工作能力下降的患者半数在14天内恢复了以前的工作状态(95%可信区间11-17天),83%在3个月内恢复。残疾(中位恢复时间31天,25-37天)和疼痛(中位58天,52-63天)则需要较长的时间才能恢复。只有72%的受试者于基线访问后12个月获得完全康复。高龄、赔偿诉讼、疼痛较重、就诊前腰背痛时间较长、就诊前因疼痛活动减少天数较多、抑郁情绪以及预期危险持续与所需恢复时问较长相关。结论在这个急性腰背痛初级保健患者队列,患者的预后并不像临床指南声称的那样乐观。多数患者的恢复缓慢。近三分之一的患者在腰背痛发作后1年尚未恢复。 | Nicholas Henschke Christopher G Maher Kathryn M Refshauge Robert D Herbert Robert G Cumming Jane Bleasel John York Anurina Das James H McAuley 蓝恭涛(译) | 2008 | 英国医学杂志中文版2008，11，6： | 2 |
| 14 | Inhibition of hepatitis C virus replication by single-stranded RNA structural mimics显示文摘AIM: To examine the effect of hepatitis C virus (HCV) structural mimics of regulatory regions of the genome on HCV replication.METHODS: HCV RNA structural mimics were constructed and tested in a HCV genotype 1b aBB7 replicon,and a Japanese fulminant hepatitis-1 (JFH-1) HCV genotype 2a infection model.All sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral RNA.Huh7.5 cells bearing the BB7 replicon or infected with JFH-1 virus were transfected with expression vectors generating HCV mimics and controls.Cellular HCV RNA and protein levels were quantified by real-time polymerase chain reaction and Western blotting,respectively.To evaluate possible antisense effects,complementary RNAs spanning a mimic were prepared.RESULTS: In the BB7 genotype 1b replicon system,mimics of the polymerase (NS-5B),X and BA regions inhibited replication by more than 90%,50%,and 60%,respectively.In the JFH-1 genotype 2 infection system,mimics that were only 74% and 46% identical in sequence relative to the corresponding region in JFH-1 inhibited HCV replication by 91.5% and 91.2%,respectively,as effectively as a mimic with complete identity to HCV genotype 2a.The inhibitory effects were confirmed by NS3 protein levels.Antisense RNA molecules spanning the 74% identical mimic had no significant effects.CONCLUSION: HCV RNA structural mimics can inhibit HCV RNA replication in replicon and infectious HCV systems and do so independent of close sequence identity with the target. | Robert Smolic Martina Smolic John H Andorfer Catherine H Wu Robert M Smith George Y Wu | 2010 | World Journal of Gastroenterology2010，16，17： | 2 |
| 15 | DNAemico-造纸厂不同生产条件下的经济分析报告系统显示文摘该系统是专门为纸厂研究的全厂范围内的经济指导软件系统。它定位于满足不同阶层管理人员在日常工作中对所需资料的准确提供 ,并确保能相互参考引用。在实际工作中 ,这些不同的原料消耗 (包括预计和和具体到单一批次产品生产 ) ,能够通过不同的组合方式和组成 ,以金融货币的方式表现出来。 | John Fogelholm 文向丰 Esa Hmlinen | 2003 | 黑龙江造纸2003，31，1： | 2 |
| 16 | 导致成人多囊肾血尿的原因显示文摘 | Robert Dedi Sunil Bhandari John H Turney Aleck M Brownjohn Ian EardLey 李寒 | 2002 | 英国医学杂志中文版2002，5，3： | 2 |
| 17 | Pancreatic paraganglioma diagnosed by endoscopic ultrasoundguided fine needle aspiration: A case report and review of literature显示文摘BACKGROUND Pancreatic paragangliomas(PPGL)are rare benign neuroendocrine neoplasms but malignancy can occur.PPGL are often misdiagnosed as pancreatic neuroendocrine tumor or pancreatic adenocarcinoma.CASE SUMMARY We reviewed 47 case reports of PPGL published in PubMed to date.Fifteen patients(15/47)with PPGL underwent endoscopic ultrasound-guided fine needle aspiration(EUS-FNA).Only six(6/15)were correctly diagnosed as PPGL.All patients with PPGL underwent surgical resection except three(one patient surgery was aborted because of hypertensive crisis,two patients had metastasis or involvement of major vessels).Our patient remained on close surveillance as she was asymptomatic.CONCLUSION Accurate preoperative diagnosis of PPGL can be safely achieved by EUS-FNA with immunohistochemistry.Multidisciplinary team approach should be considered to bring the optimal results in the management of PPGL. | Gandhi Lanke John M Stewart Jeffrey H Lee | 2021 | World Journal of Gastroenterology2021，27，37： | 2 |
| 18 | Arithmetic Coding for Data Compression 显示文摘 | Neal Radford M Cleary John G | 1987 | Communications of the ACM1987，30，6： | 1 |
| 19 | The Language of Experience:A study in Methodology显示文摘 | Erik H John M Roberts | 1956 | Memoir 13 of International Journal of American Linguistics1956，，： | 1 |
| 20 | Arithmetic coding for data compression 显示文摘 | Witten Ian H Neal Radford M Cleary John G | 1987 | Communications of the Association for Computing Machinery1987，30，6： | 1 |
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