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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 | Update in management of mesenteric ischemia显示文摘肠系膜局部缺血混乱被剥夺一或几个腹的机关遇见新陈代谢的要求足够的呼吸的一个发行量不足事件猛抛。尽管 mes 伤寒局部缺血不经常发生,死亡率从 60% ~ 100% ,依靠阻塞的消息提供者。成功的结果依赖于怀疑和迅速的管理的一个高索引。我们简短考察病理生理学和演讲各种各样是化学家实体并且在诊断和治疗考察当前的现状。尽管有在诊断和治疗的进展,迅速的诊断和支持的照顾为成功的结果仍然保持批评。新成像技术,血管内治疗和新兴的研究可以改进我们的途径到这个致命的条件。 | Robert W Chang John B Chang Walter E Longo | 2006 | World Journal of Gastroenterology2006，12，20： | 38 |
| 3 | Ligation-assisted endoscopic mucosal resection of gastric heterotopic pancreas显示文摘Heterotopic pancreas is a congenital anomaly characterized by ectopic pancreatic tissue.Treatment of heterotopic pancreas may include expectant observation,endoscopic resection or surgery.The aim of this report was to describe the technique of ligation-assisted endoscopic mucosal resection(EMR) for resection of heterotopic pancreas of the stomach.Two patients(both female,mean age 32 years) were referred for management of gastric subepithelial tumors.Endoscopic ultrasound in both disclosed small hypoechoic masses in the mucosa and submucosa.Band ligation-assisted EMR was performed in both cases without complications.Pathology from the resected tumors revealed heterotopic pancreas arising from the submucosa.Margins were free of pancreatic tissue.Ligation-assisted EMR is technically feasible and may be considered for the endoscopic management of heterotopic pancreas. | Mouen A Khashab Oscar W Cummings John M DeWitt | 2009 | World Journal of Gastroenterology2009，15，22： | 25 |
| 4 | Current status of laparoscopic and robotic ventral mesh rectopexy for external and internal rectal prolapse显示文摘External and internal rectal prolapse with their affiliated rectocele and enterocele, are associated with debilitating symptoms such as obstructed defecation, pelvic pain and faecal incontinence. Since perineal procedures are associated with a higher recurrence rate, an abdominal approach is commonly preferred. Despite the description of greater than three hundred different procedures, thus far no clear superiority of one surgical technique has been demonstrated. Ventral mesh rectopexy(VMR) is a relatively new and promising technique to correct rectal prolapse. In contrast to the abdominal procedures of past decades, VMR avoids posterolateral rectal mobilisation and thereby minimizes the risk of postoperative constipation. Because of a perceived acceptable recurrence rate, good functional results and low mesh-related morbidity in the short to medium term, VMR has been popularized in the past decade. Laparoscopic or robotic-assisted VMR is now being progressively performed internationally and several articles and guidelines propose the procedure as the treatment of choice for rectal prolapse. In this article, an outline of the current status of laparoscopic and robotic ventral mesh rectopexy for the treatment of internal and external rectal prolapse is presented. | Jan J van Iersel Tim JC Paulides Paul M Verheijen John W Lumley Ivo AMJ Broeders Esther CJ Consten | 2016 | World Journal of Gastroenterology2016，22，21： | 20 |
| 5 | Sharing Clinical Trial Data: A Proposal from the International Committee of Medical Journal Editors显示文摘The International Committee of Medical Journal Editors (ICMJE) believes that there is an ethical obligation to responsibly share data generated by interventional clinical trials because participants have put themselves at risk.In a growing consensus,many funders around the world-foundations,government agencies,and industry-now mandate data sharing.Here,we outline ICMJE's proposed requirements to help meet this obligation.We encourage feedback on the proposed requirements.Anyone can provide feedback at www.icmje.org by April 18,2016. | Darren B Taichman Joyce Backus Christopher Baethge Howard Bauchner Peter W de Leeuw Jeffrey M Drazen John Fletcher Frank Frizelle Irish Groves Abraham Haileamlak Astrid James Christine Laine Larry Peiperl Anja Pinborg Peush Sahni Si-Nan Wu | 2016 | Chinese Medical Journal2016，，2： | 20 |
| 6 | Mixed methods and survey research in family medicine and community health显示文摘Many family medicine and community health researchers use surveys as an original research methodology.Our purpose is to illustrate how survey research provides an important form of quantitative research that can be effectively combined with qualitative data to form a mixed methods study.We first provide an overview of the key principles in survey research and in mixed methods research.We review the various ways that survey can be used in mixed methods studies,citing options such as beginning a study with a survey,using a survey as the second form of data collection,or combining a survey and a form of qualitative data in a single data collection procedure.Finally,we illustrate in a specific example six steps in conducting a mixed methods study using survey research.In a mixed methods study using a survey,primary care researchers should consider six steps.Step 1.Articulate the rationale for mixed methods study.Step 2.Detail quantitative and qualitative databases.Step 3.Identify a mixed methods design.Step 4.Analyse and report the results of the quantitative and qualitative databases.Step 5.Present and show integration.Step 6.Explicate the value of using mixed methods.The ability to combine and integrate survey research into a mixed methods study provides a more rigorous approach to research than conducting only a survey or conducting just a qualitative interview.While requiring skills beyond traditional survey approaches,surveys in primary care offers an opportunity for a high level of sophistication in research methodology. | John W Creswell Mariko Hirose | 2019 | Family Medicine and Community Health2019，7，2： | 16 |
| 7 | Beyond the Pediatric end-stage liver disease system: Solutions for infants with biliary atresia requiring liver transplant显示文摘Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant. | Mary Elizabeth M Tessier Sanjiv Harpavat Ross W Shepherd Girish S Hiremath Mary L Brandt Amy Fisher John A Goss | 2014 | World Journal of Gastroenterology2014，20，32： | 14 |
| 8 | A novel chemopreventive strategy based on therapeutic microRNAs produced in plants显示文摘 | Sizolwenkosi Mlotshwa Gail J Pruss John L MacArthur Matthew W Endres Celestia Davis Lome J Hofseth Maria Marjorette Pena Vicki Vance | 2015 | Cell Research2015，25，4： | 12 |
| 9 | 激光雷达研制及其探测大气气溶胶的实验研究(英文)显示文摘作为一种激光探测大气气溶胶特征的新技术 ,采用分子滤波技术的高光谱分辨率激光雷达在国际上得到了发展。给出了对这种YAG激光雷达系统的理论分析并建立了实验装置 ,其接收望远镜孔径为 30 0mm ,YAG激光脉冲能量为 15 0mJ。通过数值模拟与初步测量估计了激光雷达性能 ,测量了大气回向散射信号 ,测量结果表明实验结果与理论分析一致。 | 刘智深 吴东 宋小全 刘金涛 John W/Hair | 2001 | 光学学报2001，21，6： | 8 |
| 10 | 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 |
| 11 | Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease显示文摘AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. | Christopher Leung Chandana B Herath Zhiyuan Jia Sof Andrikopoulos Bronwyn E Brown Michael J Davies Leni R Rivera John B Furness Josephine M Forbes Peter W Angus | 2016 | World Journal of Gastroenterology2016，22，35： | 7 |
| 12 | Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma显示文摘Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed. | Erik W Larson Halloran E Peterson Wayne T Lamoreaux Alexander R MacKay Robert K Fairbanks Jason A Call Jonathan D Carlson Benjamin C Ling John J Demakas Barton S Cooke Christopher M Lee | 2014 | World Journal of Clinical Oncology2014，5，2： | 5 |
| 13 | Football injuries of the ankle: A review of injury mechanisms, diagnosis and management显示文摘Football is the most popular sport worldwide and is associated with a high injury rate, most of which are the result of trauma from player contact. Ankle injuries are among the most commonly diagnosed injuries in the game. The result is reduced physical activity and endurance levels, lost game time, and considerable medical cost. Sports medicine professionals must employ the correct diagnostic tools and effective treatments and rehabilitation protocols to minimize the impact of these injuries on the player. This review examines the diagnosis, treatment, and postoperative rehabilitation for common football injuries of the ankle based on the clinical evidence provided in the current literature. | Raymond J Walls Keir A Ross Ethan J Fraser Christopher W Hodgkins Niall A Smyth Christopher J Egan James Calder John G Kennedy | 2016 | World Journal of Orthopedics2016，7，1： | 5 |
| 14 | 家庭医学专业的理论框架(二)显示文摘 | John W SaultzMD 梁万年 李航 | 2002 | 中国全科医学2002，5，4： | 5 |
| 15 | 抗炎介质表达缺陷参与中性粒细胞型支气管哮喘发病机制:半乳糖凝集素-3和白细胞介素-1RA/白细胞介素-1beta比例显著下降显示文摘支气管哮喘(哮喘)是具有异质性的气道炎症性疾病,其主要特点表现为气道高反应和可变的气流受限。在哮喘的发病机制中,过敏原诱导的TH2淋巴细胞激活以及IL-5介导的嗜酸粒细胞渗出起到重要的作用。近年来发现超过50%的哮喘患者气道的嗜酸粒细胞水平并不增高,并将这种亚型定义为非嗜酸粒细胞型哮喘。其中部分患者表现为气道中性粒细胞明显增高,称为中性粒细胞型哮喘。 | 高鹏 Peter G Gibson Katherine J Baines Ian A Yang John W Upham Paul N Reynolds Sandra Hodge Alan L James Christine Jenkins Matthew J Peters 张捷 Jodie L Simpson | 2016 | 中华结核和呼吸杂志2016，39，11： | 5 |
| 16 | Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis显示文摘The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types.Although a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely understood.Here,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.Using an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)cells.Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,respectively.Mechanistically,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice.Accordingly,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors.In summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance.Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention. | Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng | 2021 | Cellular & Molecular Immunology2021，18，4： | 5 |
| 17 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | The Lancet2010，，9726： | 4 |
| 18 | Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade显示文摘 | Clifford R Jack David S Knopman William J Jagust Leslie M Shaw Paul S Aisen Michael W Weiner Ronald C Petersen John Q Trojanowski | 2010 | Lancet Neurology2010，，1： | 4 |
| 19 | Prostate cancer upgrading or downgrading of biopsy Gleason scores at radical prostatectomy:prediction of'regression to the mean'using routine clinical features with correlating biochemical relapse rates显示文摘Recommendations for managing clinically localized prostate cancer are structured around clinical risk criteria,with prostate biopsy(PB)Gleason score(GS)being the most important factor.Biopsy to radical prostatectomy(RP)specimen upgrading/downgrading is welldescribed,and is often the ratio nale for costly imaging or genomic studies.We prese nt simple,no-cost an a lyses of clinical parametersto predict which GS 6 and GS 8 patients will change to GS 7 at prostatectomy.From May 2006 to December 2012,1590 patientsunderwent robot-assisted radical prostatectomy(RARP).After exclusions,we identified a GS 6 cohort of 374 patients and a GS 8cohort of 91 patients.During this era,>1000 additional patients were enrolled in an active surveillanee(AS)program.For GS 6,265(70.9%)of 374 patients were upgraded,and the cohort included 183(48.9%)patients eligible for AS by the Prostate Cancer ResearchInternational Active Surveillance Study(PRIAS)standards,of which 57.9%were upgraded.PB features that predicted a>90%chanceof upgrading included≥7 cores positive,maximum foci length≥8 mm in any core,and total tumor involvement≥30%.For GS 8,downgrading occurred in 46(50.5%),which was significantly higher for single core versus multiple cores(80.4%vs 19.6%,P=0.011).Biochemical recurre nee(BCR)occurred in 3.4%of GS 6 upgraded versus 0%non upgraded,and in GS 8,19.6%downgraded versus42.2%nondown graded.In coun seling men with clin ically localized prostate can cer,the odds of GS cha nge should be presented,andcertain men with high-volume GS 6 or low-volume GS 8 can be counseled with GS 7-based recommendations. | Muammer Altok Patricia Troncoso Mary F Achim Surena F Matin Graciela N Gonzalez John W Davis | 2019 | Asian Journal of Andrology2019，21，6： | 4 |
| 20 | 病毒性心肌炎感染模型-大鼠搏动心肌细胞培养的柯萨奇B2病毒感染研究显示文摘 | 杨英珍 John W Dyke. | 1985 | 上海医学1985，3，3： | 4 |
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