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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 | Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer显示文摘Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design. | Ganepola AP Ganepola Joel Nizin John R Rutledge David H Chang | 2014 | World Journal of Gastrointestinal Oncology2014，6，4： | 11 |
| 3 | Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer显示文摘AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION:The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer. | Ganepola AP Ganepola John R Rutledge Paritosh Suman Anusak Yiengpruksawan David H Chang | 2014 | World Journal of Gastrointestinal Oncology2014，6，1： | 9 |
| 4 | The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?显示文摘当跟随主要人的 cytomegalovirus (HCMV ) 感染的主人免疫者反应在停止病毒复制和传播通常是有效的时,病毒从来没被主人并且象所有 herpesviruses 一样清除,永久坚持。至少部分地,这坚持被知道被 HCMV 的能力便于在感染是实质上沉默的与的 myeloid 在房间建立潜伏,重要地新病毒生产的全部的缺乏。然而,尽管病毒的抄写计划很在潜伏期间被压制,很多病毒的基因在蛋白质水平在潜伏的感染期间被表示,这些中的许多被显示了在潜伏的房间和它的环境上有深刻效果。有趣地,许多也在 lysin 的感染期间这些联系潜伏的基因被表示。因此,一样的有势力主人免疫者回答为什么在 lysin 的感染期间产生了到这些病毒的基因产品,没在潜伏期间被认出,从而允许隐而不见地的感染的房间的清理,是远非清楚的。从潜伏的复活也是调停 HCMV 的疾病的一个主要原因,特别地在损害的免疫者和免疫者天真,并且也是可能的是在被建议了与象动脉粥样硬化和一些瘤形成那样的长期的疾病被联系的长期的无临床症状的 HCMV 感染的病毒的主要来源。因而,理解潜伏并且隐而不见地的感染的房间为什么看起来是 immunoprivileged,为 HCMV 的致病的理解是关键的并且可以帮助设计策略消除潜伏的病毒水库,至少在某些临床的背景。 | Mark R Wills Emma Poole Betty Lau Ben Krishna John H Sinclair | 2015 | Cellular & Molecular Immunology2015，12，2： | 6 |
| 5 | FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus显示文摘AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE~TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan~ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV. | Keyur Patel Mireen Friedrich-Rust Yoav Lurie Mircea Grigorescu Carol Stanciu Chuan-Mo Lee Eugene R Schiff Dieter Hussinger Michael P Manns Guido Gerken Isabelle Colle Michael Torbenson Erik Pulkstenis G Mani Subramanian John G McHutchison Stefan Zeuzem | 2011 | World Journal of Gastroenterology2011，17，41： | 4 |
| 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 | 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 |
| 8 | 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 |
| 9 | 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 |
| 10 | Wrappers for feature subset selection显示文摘 | Kohavi R John G H | 1997 | Artificial Intelligence1997，97，12： | 2 |
| 11 | Physiological thermoregulation in bigeye tuna, Thunnus obesus 显示文摘 | Kim N H John R S | 1994 | Environmental Biology of Eishers1994，40，： | 2 |
| 12 | Modified mixed-mode bending test apparatus for measuring delamination fracture toughness of laminated composites 显示文摘 | KUNIGAL N SHIVAKUMAR JOHN H CREWS J R Vishnu S Avva | 1998 | Journal of Composites1998，32，9： | 2 |
| 13 | Mixed-mode bending method for delamination testing 显示文摘 | James R Reeder John H Crews Jr | 1990 | AIAA Journal1990，28，7： | 2 |
| 14 | Bioremediation of uranium-contaminated groundwater: a systems approach to subsurface biogeochemistry显示文摘 | Kenneth H Williams John R Bargar Jonathan R Lloyd Derek R Lovley | 2013 | Current Opinion in Biotechnology2013，，3： | 2 |
| 15 | Wrappers for feature subset selection 显示文摘 | KOHAVI R JOHN G H | 1997 | Artificial Intelligence1997，97，： | 2 |
| 16 | Increased RhoA translocation in aorta of diabetic rats显示文摘瞄准:在糖尿病的老鼠的主动脉分析 RhoA 表示和激活。方法:男 SD 老鼠(n=70 ) 被划分成 2 个组:糖尿病的组和控制组。糖尿病被 streptozotocin (55 mg/kg ) 的静脉注射导致。老鼠 3 个星期在糖尿病的正式就职以后被学习。西方的弄污被用来测量 Rho 的表示和激活。结果:心搏率被测量 24 h/d;它在糖尿病的老鼠由 58+/-13 beats/min 减少了。当由 KCl 和血清素刺激了时,等轴的紧张证明糖尿病的主动脉的收缩显著地与控制主动脉的相比被减少。当由醋胆素刺激了时,糖尿病的主动脉的松驰被减少。在糖尿病的老鼠的大动脉的纸巾的提高的 RhoA 易位被膜界限 RhoA 的 90% 增加决定,显示 RhoA 的激活显著地在糖尿病的主动脉被增加。结论:我们的数据在调整 RhoA 上面建议那能涉及糖尿病的老鼠的脉管的机能障碍。 | Jiping TANG Ikuyo KUSAKA Amber R MASSEY Shadon ROLLINS John H ZHANG | 2006 | Acta Pharmacologica Sinica2006，27，5： | 2 |
| 17 | Validation of a FEA tire model for vehicle dynamic analysis and full vehicle real time proving ground simulations显示文摘 | Jeong W K John O H | | SAE Paper0，18，： | 1 |
| 18 | Wrappers for feature subset selection 显示文摘 | KOHAVI R JOHN G H | 1997 | artificial Intelligence Journal1997，97，1： | 1 |
| 19 | Wrappers for feature subset selection显示文摘 | Kohavi R John G H | 1997 | Artificial Intelligence1997，97，12： | 1 |
| 20 | The case for iron显示文摘 | John H Martin R Michael Gordon | 1991 | Limnol Oceanogr1991，36，8： | 1 |
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