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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 | Encapsulating peritoneal sclerosis显示文摘Encapsulating peritoneal sclerosis(EPS) is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. EPS is most commonly associated with long-term peritoneal dialysis, though medications, peritoneal infection, and systemic inflammatory disorders have been implicated. Many cases remain idiopathic. Diagnosis is often delayed given the rarity of the disorder combined with non-specific symptoms and laboratory findings. Although cross-sectional imaging with computed tomography of the abdomen can be suggestive of the disorder, many patients undergo exploratory laparotomy for diagnosis. Mortality approaches 50% one year after diagnosis. Treatment for EPS involves treating the underlying condition or eliminating possible inciting agents(i.e. peritoneal dialysis, medications, infections) and nutritional support, frequently with total parenteral nutrition. EPSspecific treatment depends on the disease stage. In the inflammatory stage, corticosteroids are the treatment of choice, while in the fibrotic stage, tamoxifen may be beneficial. In practice, distinguishing between stages may be difficult and both may be used. Surgical intervention, consisting of peritonectomy and enterolysis, is timeconsuming and high-risk and is reserved for situations in which conservative medical therapy fails in institutions with surgical expertise in this area. Herein we review the available literature of the etiology, pathogenesis, diagnosis, and treatment of this rare, but potentially devastating disease. | Christopher J Danford Steven C Lin Martin P Smith Jacqueline L Wolf | 2018 | World Journal of Gastroenterology2018，24，28： | 13 |
| 3 | MicroRNA regulation of innate immune responses in epithelial cells显示文摘Mucosal surface epithelial cells are equipped with several defense mechanisms that guard against pathogens.Recent studies indicate that microRNAs(miRNAs)mediate post-transcriptional gene suppression and may be a critical component of the complex regulatory networks in epithelial immune responses.Transcription of miRNA genes in epithelial cells can be elaborately controlled through pathogen recognition receptors,such as Toll-like receptors(TLRs),and associated nuclear factor kappaB(NF-kB)and mitogen-activated protein kinase(MAPK)pathways,and ultimately nuclear transcription factor associated-transactivation and transrepression.Activation of these intracellular signaling pathways may also modulate the process of miRNA maturation.Functionally,miRNAs may modulate epithelial immune responses at every step of the innate immune network,including production and release of cytokines/chemokines,expression of adhesion and costimulatory molecules,shuttling of miRNAs through release of exosomes and feedback regulation of immune homeostasis.Therefore,miRNAs act as critical regulators to the fine-tuning of epithelial immune responses. | Rui Zhou Steven P O’Hara Xian-Ming Chen | 2011 | Cellular & Molecular Immunology2011，8，5： | 13 |
| 4 | 静脉血栓栓塞症的抗血栓治疗:美国《胸科学》杂志指南显示文摘包括深静脉血栓和肺栓塞在内的静脉血栓栓塞症是癌症患者的主要并发症,发生率为4%~20%,并且是常见的潜在致命性急症。本文介绍了美国《胸科学》杂志指南中VET的抗血栓治疗的部分内容,其以第9版《美国胸内科医师学会循证临床实践指南》中的《静脉血栓栓塞症的抗血栓治疗:抗血栓治疗和阻止血栓形成》一文为参照,基于静脉血栓栓塞症治疗的Ⅲ期试验的发表年份,对口服抗凝剂(达比加群、利伐沙班、阿哌沙班、依度沙班)进行先后阐述(但是这一排序并不是指南专家组对药剂的优劣排序),以为临床医生提供参考。 | Kearon C Akl EA Ornelas J Blaivas A Jimenez D Bounameaux H Huisman M King CS MorrisT Sood N Stevens SM Vintch JRE Wells P Woller SC Moores CL 本刊编辑部 | 2016 | 中国全科医学2016，19，9： | 10 |
| 5 | National trends in resection of the distal pancreas显示文摘AIM:To investigate national trends in distal pancreatectomy(DP) through query of three national patient care databases.METHODS:From the Nationwide Inpatient Sample(NIS,2003-2009),the National Surgical Quality Improvement Project(NSQIP,2005-2010),and the Surveillance Epidemiology and End Results(SEER,2003-2009) databases using appropriate diagnostic and procedural codes we identified all patients with a diagnosis of a benign or malignant lesion of the body and/or tail of the pancreas that had undergone a partial or distal pancreatectomy.Utilization of laparoscopy was defined in NIS by the International Classification of Diseases,Ninth Revision correspondent procedure code;and in NSQIP by the exploratory laparoscopy or unlisted procedure current procedural terminology codes.In SEER,patients were identified by the International Classification of Diseases for Oncology,Third Edition diagnosis codes and the SEER Program Code Manual,third edition procedure codes.We analyzed the databases with respect to trends of inpatient outcome metrics,oncologic outcomes,and hospital volumes in patients with lesions of the neck and body of the pancreas that underwent operative resection.RESULTS:NIS,NSQIP and SEER identified 4242,2681 and 11 082 DP resections,respectively.Overall,laparoscopy was utilized in 15%(NIS) and 27%(NSQIP).No significant increase was seen over the course of the study.Resection was performed for malignancy in 59%(NIS) and 66%(NSQIP).Neither patient Body mass index nor comorbidities were associated with operative approach(P = 0.95 and P = 0.96,respectively).Mortality(3% vs 2%,P = 0.05) and reoperation(4% vs 4%,P = 1.0) was not different between laparoscopy and open groups.Overall complications(10% vs 15%,P < 0.001),hospital costs [44 741 dollars,interquartile range(IQR) 28 347-74 114 dollars vs 49 792 dollars,IQR 13 299-73 463,P = 0.02] and hospital length of stay(7 d,IQR 4-11 d vs 7 d,IQR 6-10,P < 0.001) were less when laparoscopy was utilized.One and two year survival after resection for malignancy were unchanged over the course of the study(ductal adenocarinoma 1-year 63.6% and 2-year 35.1%,P = 0.53;intraductal papillary mucinous neoplasm and nueroendocrine 1-year 90% and 2-year 84%,P = 0.25).The majority of resections were performed in teaching hospitals(77% NIS and 85% NSQIP),but minimally invasive surgery(MIS) was not more likely to be used in teaching hospitals(15% vs 14%,P = 0.26).Hospitals in the top decile for volume were more likely to be teaching hospitals than lower volume deciles(88% vs 43%,P < 0.001),but were no more likely to utilize MIS at resection.Complication rate in teaching and the top decile hospitals was not significantly decreased when compared to non-teaching(15% vs 14%,P = 0.72) and lower volume hospitals(14% vs 15%,P = 0.99).No difference was seen in the median number of lymph nodes and lymph node ratio in N1 disease when compared by year(P = 0.17 and P = 0.96,respectively).CONCLUSION:There appears to be an overall underutilization of laparoscopy for DP.Centralization does not appear to be occurring.Survival and lymph node harvest have not changed. | Armando Rosales-Velderrain Steven P Bowers Ross F Goldberg Tatyan M Clarke Mauricia A Buchanan John A Stauffer Horacio J Asbun | 2012 | World Journal of Gastroenterology2012，18，32： | 8 |
| 6 | Gastroenteropancreatic neuroendocrine tumours显示文摘 | Irvin M Modlin Kjell Oberg Daniel C Chung Robert T Jensen Wouter W de Herder Rajesh V Thakker Martyn Caplin Gianfranco Delle Fave Greg A Kaltsas Eric P Krenning Steven F Moss Ola Nilsson Guido Rindi Ramon Salazar Philippe Ruszniewski Anders Sundin | 2008 | Lancet Oncology2008，，1： | 8 |
| 7 | 腹腔镜外科学基础认证项目简介及其对中国外科医师的意义显示文摘腹腔镜外科学基础(FLS)项目是普通外科中第1个经过验证的操作和认知考核项目.FLS由美国胃肠内镜外科医师协会(SAGES)开发并得到美国外科医学委员会(ABS)的支持.ABS要求所有拟参加普通外科医师执业资格考试前必须通过FLS考试.在美国,普通外科医师执业资格考试是取得执业资格的第一步.本文回顾了FLS项目在美国取得的成功经验,并就该项目在中国推广标准化腹腔镜外科技术中的应用和获益进行了介绍. | Linda P Zhang Samuel R G Finlayson Allan Okrainec Steven D Schwaitzberg | 2014 | 中华消化外科杂志2014，13，9： | 5 |
| 8 | 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 |
| 9 | 生物素——抗结核药物新研究方向(英文)显示文摘耐药菌的出现对全球公共卫生构成了巨大的挑战,结核分枝杆菌(TB)是结核病的病原菌,是临床上最重要的病原体之一。新抗生素的研发用以治疗耐药性结核病已成为临床及公共卫生管理亟待解决的重要问题。生物素(维生素B7)在结核杆菌的代谢途径如脂肪酸合成和三羧酸循环中发挥重要作用,通过生物素蛋白连接酶连接活性辅助因子而被激活。生物素蛋白连接酶及其相关生物合成通路是微生物合成生物素过程中必不可或缺的关键分子,因而有可能成为新的药物靶点。遗传研究表明,结核杆菌需要由菌体进行生物素的全程合成,因此,生物素合成酶在在结核杆菌代谢过程中起着至关重要的作用,引起了抗结核药物研究者的高度重视。本文论述了结核杆菌生物素合成通路,并重点分析了生物素合成过程中可能成为药物靶点的关键酶,旨在为结核病的治疗提供新思路,具有重要的临床意义。 | THOMPSON Andrew P STERNICKI Louise M WEGENER Kate L 陆伟 竺丽梅 BOOKER Grant W POLYAK Steven W 李燕 | 2016 | 江苏预防医学2016，27，3： | 4 |
| 10 | Hepatocellular carcinoma after Iocoregional therapy:Magnetic resonance imaging findings in falsely negative exams显示文摘AIM:To elucidate causes for false negative magnetic resonance imaging(MRI)exams by identifying imaging characteristics that predict viable hepatocellular carcinoma(HCC)in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent.METHODS:This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy.All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrenttumor.Retrospectively,2 radiologists,blinded to clinica and pathological data,independently reviewed the pre transplant MRIs for 7 imaging features.Liver explan histopathology provided the reference standard,with clinically significant tumor defined as viable tumor≥1.0cm in maximum dimension.Fisher’s exact test was firs performed to identify significant imaging features.RESULTS:Inclusion criteria selected for 42 patients with 65 treated lesions.Fourteen of 42 patients(33%and 16 of 65 treated lesions(25%)had clinically significant viable tumor on explant histology.None o the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC.CONCLUSION:After locoregional therapy some treated lesions that do not demonstrate any MRI evidence o HCC will contain viable tumor.As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor.The possibility of occult tumo should be a consideration when contemplating any action which might delay liver transplant. | David Becker-Weidman Jesse M Civan Sandeep P Deshmukh Christopher G Roth Steven K Herrine Laurence Parker Donald G Mitchell | 2016 | World Journal of Hepatology2016，8，16： | 2 |
| 11 | The relevance of size efficiency to biomanipulation theory:a field test under hypertrophic conditions显示文摘 | Steven D Luc D M Nicole P | 1997 | Hydrobiologia1997，360，： | 2 |
| 12 | Androgen receptor functions in prostate cancer development and progression显示文摘雄激素受体(AR ) 为前列腺的正常开发并且为它的区分的函数是批评的。在前列腺癌症(PCa ) 的 AR 的一致表示,和它在 PCa 的继续的活动在雄激素剥夺治疗(阉割抵抗的前列腺癌症(CRPC )) 以后的那恶化,显示这些基因的至少一个子集为 PCa 开发和前进也是批评的。这评论探讨了 AR 可能为 PCa 批评的调整基因,并且 AR 怎么可以在 PCa 开发和前进期间获得新函数。 | Steven P Balk | 2014 | Asian Journal of Andrology2014，16，4： | 2 |
| 13 | 颈部疼痛的诊断和管理进展显示文摘颈部疼痛带来了相当大的个人和社会经济负担——它是患病率和伤残所致生命年损失前五位的慢性疼痛疾病之一——但是仅获得了背部疼痛研究的一小部分经费。尽管大多数颈部疼痛急性发作后自行消退,但有超过三分之一的患者群在一年多以后仍有轻度症状或疼痛复发,遗传和社会心理因素是症状持续存在的危险因素。将近一半的慢性颈部疼痛患者具有神经性一损伤反应性混合症状或主要为神经性症状。很少有临床研究专门针对颈部疼痛,、肌肉松弛剂和非甾体类抗炙药对急性颈部疼痛有效,临床实践主要依据其他慢性疼痛的研究结果。补充和替代疗法中,证据级别最强的就是运动,稍弱证据支持不同状况下进行按摩、针灸、瑜伽和脊椎推拿。对于神经根型颈椎病和小关节病,弱证据分别支持硬膜外类固醇注射和射频去神经支配治疗。对于大部分患者,手术在短期内比保守治疗更有效,但长期效果相似,手术前进行临床观察是一种合理策略. | Steven P Cohen W Michael Hooten 公磊 | 2018 | 英国医学杂志中文版2018，21，3： | 2 |
| 14 | Decay estimates for fourth order wave equations显示文摘 | Steven P L | 1998 | Journal of Differential Equations1998，143，： | 2 |
| 15 | Stability and instability of fourth-order solitary waves 显示文摘 | Steven P L | 1998 | Jottmal of Dynamics and Differential Equations1998，10，1： | 2 |
| 16 | Phenotypic instability and rapid gene silencing in newly formed Arabidopsis alloteraploids显示文摘 | Comai L Tyagi A P Winter K Holmes-Davis R Reynolds S H Stevens Y Byers B | 2000 | Plant Cell2000，12，9： | 2 |
| 17 | Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias显示文摘 | Steven L Higgins John D Hummel Imran K Niazi Michael C Giudici Seth J Worley Leslie A Saxon John P Boehmer Michael B Higginbotham Teresa De Marco Elyse Foster Patrick G Yong | 2003 | Journal of the American College of Cardiology2003，，8： | 2 |
| 18 | Identification and detection of Actinobacillus pleuropneumoniae by PCR based on the gene apxIVA显示文摘 | Alain S Steven P Djordjevic | 2001 | Vet Res2001，79，： | 1 |
| 19 | Resource Curse and How to Avoid it? 显示文摘 | Stevens P | 2006 | The Journal of Energy and Development2006，31，1： | 1 |
| 20 | Noninvasive surrogate markers of atherosclerosis显示文摘 | Steven BF Paolo V Francesco P | 2002 | Am J Cardiol2002，89，5： | 1 |
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