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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 | m^6A mRNA methylation sustains Treg suppressive functions显示文摘 | Jiyu Tong Guangchao Cao Ting Zhang Esen Sefik Maria Carolina Amezcua Vesely James P Broughton Shu Zhu Huabin Li Bin Li Lei Chen Howard Y Chang Bing Su Richard A Flavell Hua-Bing Li | 2018 | Cell Research2018，28，2： | 30 |
| 3 | Genetics of coronary artery disease and myocardial infarction显示文摘Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction(MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MIassociated genetic variants identified using candidate gene approaches and genome-wide association studies(GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI. | Xuming Dai Szymon Wiernek James P Evans Marschall S Runge | 2016 | World Journal of Cardiology2016，8，1： | 15 |
| 4 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 5 | 髋臼骨折后创伤性关节炎全髋关节置换疗效研究显示文摘[目的]比较髋臼骨折经切开复位内固定治疗和保守治疗后发生创伤性关节炎行全髋关节置换术的远期疗效。[方法]30例(32髋)髋臼骨折患者行保守治疗或切开复位内固定术,髋臼骨折后平均间隔7年5个月(5个月~29年)发生创伤性关节炎,对32髋行全髋关节置换术治疗,手术时平均51岁(25~78岁)。应用非骨水泥人工关节29髋,骨水泥型2髋,混合型1髋。术后平均随访8年9个月(4~17年)。[结果]手术组和保守组在骨移植、翻修率、手术时间和异位骨化发生率方面无显著差异(P>0.05);失血量有统计学差异(P<0.05),保守组失血量较多。手术组和保守组临床疗效无显著性差异。[结论]髋臼骨折行保守治疗和手术治疗后发生创伤性关节炎需行人工关节置换治疗,两者远期疗效相似,非骨水泥型关节置换疗效较好。 | 潘进社 张英泽 彭阿钦 李亚洲 张奉琪 陈伟 James P Waddell | 2008 | 中国矫形外科杂志2008，16，2： | 13 |
| 6 | Elucidation of the ‘Honeycrisp’ pedigree through haplotype analysis with a multi-family integrated SNP linkage map and a large apple (Malus×domestica) pedigree-connected SNP data set显示文摘The apple(Malus×domestica)cultivar Honeycrisp has become important economically and as a breeding parent.An earlier study with SSR markers indicated the original recorded pedigree of‘Honeycrisp’was incorrect and‘Keepsake’was identified as one putative parent,the other being unknown.The objective of this study was to verify‘Keepsake’as a parent and identify and genetically describe the unknown parent and its grandparents.A multi-family based dense and high-quality integrated SNP map was created using the apple 8 K Illumina Infinium SNP array.This map was used alongside a large pedigree-connected data set from the RosBREED project to build extended SNP haplotypes and to identify pedigree relationships.‘Keepsake’was verified as one parent of‘Honeycrisp’and‘Duchess of Oldenburg’and‘Golden Delicious’were identified as grandparents through the unknown parent.Following this finding,siblings of‘Honeycrisp’were identified using the SNP data.Breeding records from several of these siblings suggested that the previously unreported parent is a University of Minnesota selection,MN1627.This selection is no longer available,but now is genetically described through imputed SNP haplotypes.We also present the mosaic grandparental composition of‘Honeycrisp’for each of its 17 chromosome pairs.This new pedigree and genetic information will be useful in future pedigree-based genetic studies to connect‘Honeycrisp’with other cultivars used widely in apple breeding programs.The created SNP linkage map will benefit future research using the data from the Illumina apple 8 and 20 K and Affymetrix 480 K SNP arrays. | Nicholas P Howard Eric van de Weg David S Bedford Cameron P Peace Stijn Vanderzande Matthew D Clark Soon Li Teh Lichun Cai James J Luby | 2017 | Horticulture Research2017，4，1： | 9 |
| 7 | 评估清晨或夜晚服用降压药对24h动态血压的影响:清晨或夜间服用降压药的希腊英国联合研究显示文摘观察数据显示,临床血压水平与随后的主要不良心血管事件之间存在强烈的线性关系。然而,动态血压监测显示,夜间血压水平比24h或白天血压水平更能预测主要的不良心血管事件。此外,夜间与白天的血压比值和杓型状态也是心血管结局的重要独立预测因素。这些发现可能对抗高血压药物的最佳给药时间有影响,一些研究表明,夜晚服用降压药可能较白天服药减少心血管事件。 | Poulter NR Savopoulos C Anjum A Apostolopoulou M Chapman N Cross M Falaschetti E Fotiadis S James RM Kanellos I Szigeti M Thom S Sever P Thompson D Hatzitolios AI 赵狄 练桂丽 | 2018 | 中华高血压杂志2018，26，10： | 7 |
| 8 | Computed tomography and patient risk:Facts,perceptions and uncertainties显示文摘Since its introduction in the 1970s, computed tomography(CT) has revolutionized diagnostic decision-making. One of the major concerns associated with the widespread use of CT is the associated increased radiation exposure incurred by patients. The link between ionizing radiation and the subsequent development of neoplasia has been largely based on extrapolating data from studies of survivors of the atomic bombs dropped in Japan in 1945 and on assessments of the increased relative risk of neoplasia in those occupationally exposed to radiation within the nuclear industry. However, the association between exposure to low-dose radiation from diagnostic imaging examinations and oncogenesis remains unclear. With improved technology, significant advances have already been achieved with regards to radiation dose reduction. There are several dose optimization strategies available that may be readily employed including omitting unnecessary images at the ends of acquired series, minimizing the number of phases acquired, and the use of automated exposure control as opposed to fixed tube current techniques. In addition, new image reconstruction techniques that reduce radiation dose have been developed in recent years with promising results. These techniques use iterative reconstruction algorithms to attain diagnostic quality images with reduced image noise at lower radiation doses. | Stephen P Power Fiachra Moloney Maria Twomey Karl James Owen J O'Connor Michael M Maher | 2016 | World Journal of Radiology2016，8，12： | 7 |
| 9 | Assessment of stable coronary artery disease by cardiovascular magnetic resonance imaging: Current and emerging techniques显示文摘Coronary artery disease(CAD) is a leading cause of death and disability worldwide. Cardiovascular magnetic resonance(CMR) is established in clinical practice guidelines with a growing evidence base supporting its use to aid the diagnosis and management of patients with suspected or established CAD. CMR is a multi-parametric imaging modality that yields high spatial resolution images that can be acquired in any plane for the assessment of global and regional cardiac function, myocardial perfusion and viability, tissue characterisation and coronary artery anatomy, all within a single study protocol and without exposure to ionising radiation. Advances in technology and acquisition techniques continue to progress the utility of CMR across a wide spectrum of cardiovascular disease, and the publication of large scale clinical trials continues to strengthen the role of CMR in daily cardiology practice. This article aims to review current practice and explore the future directions of multi-parametric CMR imaging in the investigation of stable CAD. | James RJ Foley Sven Plein John P Greenwood | 2017 | World Journal of Cardiology2017，9，2： | 6 |
| 10 | Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention显示文摘Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed. | Richard A Brogan Christopher J Malkin Philip D Batin Alexander D Simms James M McLenachan Christopher P Gale | 2014 | World Journal of Cardiology2014，6，8： | 6 |
| 11 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 12 | Role of self-expanding metal stents in the management ofvariceal haemorrhage:Hype or hope?显示文摘Despite the advances of medical,endoscopic and radiological therapy over recent years the mortality rates of acute variceal haemorrhage are still 16%-20% and the medium term outcome has not improved in the last 25 years. Early transjugular intrahepatic portosystemic shunt has proved to be an effective therapy for selected groups of patients with a high risk of re-bleeding and moderate liver disease. However,there is an unmet need for a therapy that can be applied in patients with a high risk of re-bleeding and advanced liver disease either as definitive therapy or as a bridge to permanent therapy. Selfexpanding metal stents can be placed without the need for endoscopic or fluoroscopic control and,once in place,will provide effective haemostasis and allow a route for oral fluids and nutrition. They can remain in place whilst liver function recovers and secondary prophylaxis is initiated. We review the results of 6 case series including a total of 83 patients and the first randomised controlled trial of self-expanding metal stents vs balloon tamponade(BT) in the management of refractory variceal haemorrhage. We report that self-expanding metal stents provide effective haemostasis and perform better than BT in refractory bleeding,where they are associated with fewer complications. Whilst the most effective place for self-expanding metal stents in the management algorithm needs to be determined by further randomised controlled trials,currently they provide an effective alternative to BT in selected patients. | Brian J Hogan James P O’Beirne | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，1： | 5 |
| 13 | N-acetylcysteine treats intravenous amiodarone induced liver injury显示文摘We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver enzymes.While the specific mechanisms for the pathogenesis of IV amiodaroneDILI and the therapeutic action of IV NAC are both unknown, this case strongly implies at least some commonality.Because IV amiodarone is indicated for the treatment of serious cardiac arrhythmias in an intensive care unit setting, some degree of ischemic hepatitis is likely a cofactor in most cases. | Matthew L Mudalel Kartikeya P Dave James P Hummel Steven F Solga | 2015 | World Journal of Gastroenterology2015，21，9： | 5 |
| 14 | COVID-19: An overview and a clinical update显示文摘The outbreak of coronavirus disease-2019(COVID-19,previously known as 2019 nCoV)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in Wuhan City,China,has spread rapidly around the world.Most patients from the first cluster had an epidemiological connection to the Wuhan's Huanan Seafood Wholesale Market.Available evidence has shown that SARSCoV-2 can be easily transmitted from person to person through close contact and respiratory droplets,posing a substantial challenge to public health.At present,the research on SARS-CoV-2 is still in the primary stages.However,dexamethasone and remdesivir are appeared to be promising medical therapies.Still,there is no definite specific treatment,and the mainstay of treatment is still focused on supportive therapies.Currently,over 150 vaccines are under investigation.It is necessary to understand the nature of the virus and its clinical characteristics in order to find effectively manage the disease.The knowledge about this virus is rapidly evolving,and clinicians must update themselves regularly.The present review comprehensively summarizes the epidemiology,pathogenesis,clinical characteristics,and management of COVID-19 based on the current evidence. | Arunkumar Krishnan James P Hamilton Saleh A Alqahtani Tinsay A Woreta | 2021 | World Journal of Clinical Cases2021，9，1： | 5 |
| 15 | 生长因子及其前景显示文摘本综述说明目前在研究的生物学反应改良因子将作为生长因子广泛地用于加速创伤愈合。简明阐述了生长因子的功能以及对动物与临床方面的研究概况,并且讨论了这些因子在未来眼科治疗领域中的重要意义。 | James P Gills 周文天 | 1990 | 国外医学(眼科学分册)1990，14，3： | 5 |
| 16 | Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus显示文摘AIM:To assess tumour regression grade(TRG)and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS:Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005and 2011 at a single institution were reviewed.Triplet neoadjuvant chemotherapy consisting of platinum,fluoropyrimidine and anthracycline was considered for operable patients(World Health Organization performance status≤2)with clinical stage T2-4 N0-1.Response to neoadjuvant chemotherapy(NAC)was assessed using TRG,as described by Mandard et al.In addition lymph node downstaging was also assessed.Lymph node downstaging was defined by cN1 at diagnosis:assessed radiologically(computed tomography,positron emission tomography,endoscopic ultrasonography),then pathologically recorded as N0 after surgery;ypN0 if NAC given prior to surgery,or pN0if surgery alone.Patients were followed up for 5 years post surgery.Recurrence was defined radiologically,with or without pathological confirmation.An association was examined between t TRG and lymph node downstaging with disease free survival(DFS)and a comprehensive range of clinicopathological characteristics.RESULTS:Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years(median follow up:2.552,95%CI:2.022-3.081).There was a 1.8%(n=4)inpatient mortality rate.One hundred and thirty-six(62.4%)patients received NAC,with 74.3%(n=101)of patients demonstrating some signs of pathological tumour regression(TRG 1-4)and 5.9%(n=8)having a complete pathological response.Forty four point one percent(n=60)had downstaging of their nodal disease(cN1 to ypN0),compared to only 15.9%(n=13)that underwent surgery alone(pre-operatively overstaged:cN1 to pN0),(P<0.0001).Response to NAC was associated with significantly increased DFS(mean DFS;TRG 1-2:5.1years,95%CI:4.6-5.6 vs TRG 3-5:2.8 years,95%CI:2.2-3.3,P<0.0001).Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC(median DFS;TRG 3-5 and nodal down-staging:5.533 years,95%CI:3.558-7.531 vs TRG 3-5 and no nodal down-staging:1.114 years,95%CI:0.961-1.267,P<0.0001).CONCLUSION:Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. | Fergus Noble Luke Nolan Adrian C Bateman James P Byrne Jamie J Kelly Ian S Bailey Donna M Sharland Charlotte N Rees Timothy J Iveson Tim J Underwood Andrew R Bateman | 2013 | World Journal of Gastroenterology2013，19，48： | 4 |
| 17 | Apoptosis commitment- translating survival signals into decisions on mitochondria显示文摘最有缺点、讨厌的房间由 apoptosis 死,为没有损坏包围织物,移开如此的房间的一个精致地控制的基因计划。一旦一个房间承诺了 apoptosis,这个过程是显著地有效的,并且在开始的一些分钟以内被完成。为一个 apoptotic 房间的没有回来的这个点通常被坚持是外部 mitochondrial 膜是 permeabilised 的在点,一个过程由蛋白质的 Bcl-2 家庭调整了。这些蛋白质怎么调整这个决定点,对象 apoptotic 控制被失去的癌症那样的疾病中央。在这评论,我们将讨论 apoptotic 发信号并且一个房间怎么做不可逆的决定死。我们将集中于幸存信号,对细胞外的矩阵(ECM ) 的房间粘附导出的那些,和使用的一个集合这些加亮 apoptotic 发信号的复杂性。特别地,我们将说明多重发信号小径怎么收敛决定批评房间命运决定。 | James A Keeble Andrew P Gilmore | 2007 | Cell Research2007，17，12： | 4 |
| 18 | Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial显示文摘 | JY Douillard D Cunningham AD Roth M Navarro RD James P Karasek P Jandik T Iveson J Carmichael M Alakl G Gruia L Awad P Rougier | 2000 | The Lancet2000，，9209： | 4 |
| 19 | A post-classical theory of enamel biomineralization… and why we need one显示文摘Enamel crystals are unique in shape,orientation and organization.They are hundreds of thousands times longer than they are wide,run parallel to each other,are oriented with respect to the ameloblast membrane at the mineralization front and are organized into rod or interrod enamel.The classical theory of amelogenesis postulates that extracellular matrix proteins shape crystallites by specifically inhibiting ion deposition on the crystal sides,orient them by binding multiple crystallites and establish higher levels of crystal organization.Elements of the classical theory are supported in principle by in vitro studies;however,the classical theory does not explain how enamel forms in vivo.In this review,we describe how amelogenesis is highly integrated with ameloblast cell activities and how the shape,orientation and organization of enamel mineral ribbons are established by a mineralization front apparatus along the secretory surface of the ameloblast cell membrane. | James P Simmer Amelia S Richardson Yuan-Yuan Hu Charles E Smith Jan Ching-Chun Hu | 2012 | International Journal of Oral Science2012，4，3： | 4 |
| 20 | Endoscopist's approach to nutrition in the patient with pancreatitis显示文摘Nutritional therapy has an important role in the management of patient with severe acute pancreatitis.This article reviews the endoscopist's approach to manage nutrition in such cases.Enteral feeding has been clearly validated as the preferred route of feeding,and should be started early on admission.Parenteral nutrition should be reserved for patients with contraindications to enteral feeding such as small bowel obstruction.Moreover,nasogastric feeding is safe and as effective as nasojejunal feeding.If a prolonged course of enteral feeding(>30d) is required,endoscopic placement of feeding gastrostomy or jejunostomy tubes should be considered. | Shahzad Iqbal Jay P Babich James H Grendell David M Friedel | 2012 | World Journal of Gastrointestinal Endoscopy2012，4，12： | 4 |
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