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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 | Rotational assisted endoscopic retrograde cholangiopancreatography in patients with reconstructive gastrointestinal surgical anatomy显示文摘AIM: To evaluate the success rates of performing therapy utilizing a rotational assisted enteroscopy device in endoscopic retrograde cholangiopancreatography(ERCP) in surgically altered anatomy patients. METHODS: Between June 1, 2009 and November 8, 2012, we performed 42 ERCPs with the use of rotational enteroscopy for patients with altered anatomy(39 with gastric bypass Roux-en-Y, 2 with Billroth Ⅱ gastrectomy, and 1 with hepaticojejunostomy associated with liver transplant). The indications for ERCP were: choledocholithiasis: 13 of 42(30.9%), biliary obstruction suggested on imaging: 20 of 42(47.6%), suspected sphincter of Oddi dysfunction: 4 of 42(9.5%), abnormal liver enzymes: 1 of 42(2.4%), ascending cholangitis: 2 of 42(4.8%), and bile leak: 2 of 42(4.8%). All procedures were completed with the Olympus SIF-Q180 enteroscope and the Endo-Ease Discovery SB overtube produced by Spirus Medical. RESULTS: Successful visualization of the major ampulla was accomplished in 32 of 42 procedures(76.2%). Cannulation of the bile duct was successful in 26 of 32 procedures reaching the major ampulla(81.3%). Successful therapeutic intervention was completed in 24 of 26 procedures in which the bileduct was cannulated(92.3%). The overall intention to treat success rate was 64.3%. In terms of cannulation success, the intention to treat success rate was 61.5%. Ten out of forty two patients(23.8%) required admission to the hospital after procedure for abdominal pain and nausea, and 3 of those 10 patients(7.1%) had a diagnosis of post-ERCP pancreatitis. The average hospital stay was 3 d.CONCLUSION: It is reasonable to consider an attempt at rotational assisted ERCP prior to a surgical intervention to alleviate biliary complications in patients with altered surgical anatomy. | Majed El Zouhairi James B Watson Svetang V Desai David K Swartz Alejandra Castillo-Roth Mahfuzul Haque Paul S Jowell Malcolm S Branch Rebecca A Burbridge | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，3： | 10 |
| 3 | Clarifying sub-genomic positions of QTLs for flowering habit and fruit quality in U.S. strawberry (Fragaria×ananassa) breeding populations using pedigree-based QTL analysis显示文摘The cultivated strawberry(Fragaria×ananassa)is consumed worldwide for its flavor and nutritional benefits.Genetic analysis of commercially important traits in strawberry are important for the development of breeding methods and tools for this species.Although several quantitative trait loci(QTL)have been previously detected for fruit quality and flowering traits using low-density genetic maps,clarity on the sub-genomic locations of these QTLs was missing.Recent discoveries in allo-octoploid strawberry genomics led to the development of the IStraw90 single-nucleotide polymorphism(SNP)array,enabling high-density genetic maps and finer resolution QTL analysis.In this study,breeder-specified traits were evaluated in the Eastern(Michigan)and Western(Oregon)United States for a common set of breeding populations during 2 years.Several QTLs were validated for soluble solids content(SSC),fruit weight(FWT),pH and titratable acidity(TA)using a pedigree-based QTL analysis approach.For fruit quality,a QTL for SSC on linkage group(LG)6A,a QTL for FWT on LG 2BII,a QTL for pH on LG 4CII and two QTLs for TA on LGs 2A and 5B were detected.In addition,a large-effect QTL for flowering was detected at the distal end of LG 4A,coinciding with the FaPFRU locus.Marker haplotype analysis in the FaPFRU region indicated that the homozygous recessive genotype was highly predictive of seasonal flowering.SNP probes in the FaPFRU region may help facilitate marker-assisted selection for this trait. | Sujeet Verma Jason D Zurn Natalia Salinas Megan M Mathey Beatrice Denoyes James F Hancock Chad E Finn Nahla V Bassil Vance M Whitaker | 2017 | Horticulture Research2017，4，1： | 10 |
| 4 | Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency显示文摘Pluripotency,一个细胞的能力区分并且产生所有胚胎的系,定义象胚胎的茎(ES ) 那样的哺乳动物的细胞类型的一个小数字细胞。当它通常被保持了时,那 pluripotency 是 transcriptional 的产品激活并且维持关键干细胞基因的表达式的规章的网络,积累的证据在建立并且保卫 ES 房间的 pluripotency 为 epigenetic 进程正在指向一个关键角色,象维持区分的房间类型的身份一样。以便更好在 pluripotency 理解 epigenetic 机制的角色,我们检验了在经历区别进一个 mesendodermal 系的人的 ES 房间(hESCs ) 染色体宽的染色质修正的动力学。我们发现在倡导者的染色质修正在区别期间仍然保持大部分不变,除了在在在 H3K27 的 acetylation 和 methylation 之间的一个动态开关标记在基因表示的激活和 silencing 之间的转变的倡导者的一个小数字,建议在在大多数差别上的房间命运承诺的一个层次表示了基因。我们也在 50 000 潜在的 enhancers 上印射,并且在染色质修正,特别 H3K4me1 和 H3K27ac 观察了大得多的动力学,它与他们的潜在的目标基因的表示相关。这些 enhancers 的进一步的分析揭示了 pluripotency 和可以在 hESCs 授与发展胜任的一个平衡状态的一口染色质签名陈述语气的潜在地关键的 transcriptional 管理者。我们的结果提供在定义 enhancers 和 pluripotency 支持染色质修正的角色的新证据。 | R David Hawkins Gary C Hon Chuhu Yang Jessica E Antosiewicz-Bourget Leonard K Lee Que-Minh Ngo Sarit Klugman Keith A Ching Lee E Edsall Zhen Ye Samantha Kuan Pengzhi Yu Hui Liu Xinmin Zhang Roland D Green Victor V Lobanenkov Ron Stewart James A Thomson Bing Ren | 2011 | Cell Research2011，21，10： | 6 |
| 5 | 直接评估吗啡刺激糖尿病人隐静脉内皮一氧化氮释放减少显示文摘to directly measure in real time basal and stimulated levels of NO released from human saphenous vein endothelium and to quantify the expression of the μopiate receptor, which has been linked with NO release. METHODS: Saphenous vein segments from patients with type 2 diabetes ( n = 12) and patients without diabetes (n =8) were obtained. The release of NO was measured directly from the endothelium using a NO-specific amperometric probe. NΩ-nitro-L-arginine methyl ester (L-NAME, 0.1 mmol/L), a NO synthase (NOS) inhibitor, or morphine (1 μmol/L), a stimulant, was administered and the measurements were repeated. Values were reported relative to the mean initial measurement of NO release from diabetic endothelium, which was defined as the relative zero level of NO release. A RT-PCR was then performed on the endothelium to measureμ opiate receptor expression. RESULTS: Diabetic patients (n = 12) showed a relative and significantly diminished basal level of released NO, (0.049± 0.012) nmol/L, compared | Thomas V BILHNGER, James A VOSSWINKEL, Patrick CADET, Christos M RIALAS, Harold I MAGAZINE, George B STEFANO(Division of Cardiothoracic Surgery, Department of Surgery, University Hospital and Medical Center, HSC, T19-080, Stony Brook, New York 11794-8191 Neuroscience Research Institute, State University of New York College at Old Westbury, Old Westbury, New York , USA) | 2002 | Acta Pharmacologica Sinica2002，23，2： | 3 |
| 6 | A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report 1 1 Original Contributions is coordinated by John A. Marx , MD, of Carolinas Medical Center, Charlotte, North Carolina显示文摘 | David Bar–Or Edward Lau James V Winkler | 2000 | Journal of Emergency Medicine2000，，4： | 3 |
| 7 | 成年小鼠中枢神经系统损伤后TT-301可抑制小胶质细胞活化及改善其预后(英文)显示文摘BACKGROUND Microglial inhibition may reduce secondary tissue injury and improve functional outcome following acute brain injury.Utilizing clinically relevant murine models of traumatic brain injury and intracerebral hemorrhage,neuroinflammatory responses and functional | James ML Cantillana V Kernagis DN Dawson HN Klaman LD Laskowitz DT | 2012 | 中华神经外科疾病研究杂志2012，11，2： | 3 |
| 8 | Ankle Fractures in the Elderly: What You Get Depends on Where You Live and Who You See显示文摘 | Kenneth J Koval Jon Lurie Weiping Zhou Michael B Sparks Robert V Cantu Scott M Sporer James Weinstein | 2005 | Journal of Orthopaedic Trauma2005，，9： | 2 |
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| 11 | NonParametric tests for trends in wa- ter quality 显示文摘 | Gerald V B James P H | 2001 | Water Resources Research2001，37，4： | 1 |
| 12 | Effects of pH on heavy metal sorption on mineral apatite显示文摘 | Chen XB Judith V James LC | 1997 | Environmental Science & Technology1997，31，3： | 1 |
| 13 | Clay nanolayer reinforcement of cis-1,4-polyisoprene and epoxidized natural rubber 显示文摘 | Yen V James M | 2001 | J Appl Polym Sci2001，82，6： | 1 |
| 14 | Lactobacillus rhamnosus GG decreases TNF- α production in lipopolysaccharide-activated marine macrophages by a contact-independent mechanism显示文摘 | JEREMY A JAMES V | 2003 | Cellular Microbiology2003，5，4： | 1 |
| 15 | Larrick Antibody engineering at the millennium显示文摘 | James W | 2000 | BioTchniques2000，29，1： | 1 |
| 16 | The generalized Fresnel transform and its applications to optics显示文摘 | James D F V Agarwal G S | 1996 | Opt Commun1996，126，： | 1 |
| 17 | Analysis of the efficacy and safety of excimer laser PTK in the treatment of corneal disease显示文摘 | Stephen J Zuckerman James V Aquavella Steve B Park | 1996 | Cornea1996，15，1： | 1 |
| 18 | Polymorphisms of TLR4 but not CD14 are associated with a decreased risk of aggressive periodontitis显示文摘 | JAMES J A POULTON K V HAWORTH S E | 2007 | J Clin Periodontol2007，34，2： | 1 |
| 19 | Characterization of Phytophthora infestans in Wisconsin from 1993 to 1995显示文摘 | Marshall-Farm K D Mcgrath M James R V | 1998 | Plant Disease1998，82，4： | 1 |
| 20 | A Unique Clonal JAK2 Mutation Leading to Constitutive Signaling Causes Polyeythaemia Vera显示文摘 | James C Ugo V Couedic J P I | 2005 | Nature2005，434，7037： | 1 |
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