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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | 非胰岛素依赖型糖尿病冠状动脉疾病的危险因素:英国糖尿病前瞻性研究(UKPDS:23)显示文摘目的:评价2型糖尿病患者冠状动脉疾病的基线危险因素。设计:对2 693例资料完整的患者进行年龄和性别调整的逐步选择过程分析,以确定哪些冠状动脉疾病的危险因素应纳入 Cox 比例风险模型。对象:3 055例白人患者,平均年龄52岁,均新近诊断为2型糖尿病,且无动脉粥样硬化相关疾病的证据。平均随访期7.9年。335例患者于10年内出现冠状动脉疾病。结局评定:具有明确异常心电图的心绞痛、致死或非致死性心肌梗塞。结果:冠状动脉疾病与低密度脂蛋白胆固醇浓度升高、高密度脂蛋白胆固醇浓度降低、甘油三酯浓度升高、高血红蛋白 A_(1c)、高收缩压、高空腹血糖以及吸烟史密切相关。低密度脂蛋白胆固醇较高1/3对较低1/3区间的估计风险比为2.26(95%可信区间为1.70~3.00),高密度脂蛋白胆固醇为0.55(0.41~0.73),血红蛋白 A_(1c)为1.52(1.15~2.01),收缩压为1.82(1.34~2.47)。吸烟者的估计风险比为1.41(1.06~1.88)。结论:2型糖尿病患者中,存在冠状动脉疾病潜在的、可变的5种危险因素的交叉重叠影响。它们是低密度脂蛋白胆固醇浓度升高、高密度脂蛋白胆固醇浓度降低、高血压、高血糖和吸烟。 | R C Turner H Millns H A W Neil I M Stratton S E Manley D R Matthews R R Holman 赵维纲 | 1998 | 英国医学杂志中文版1998，0，3： | 11 |
| 3 | Effect of alcohol exposure on hepatic superoxide generation and hepcidin expression显示文摘AIM: To understand the role of mitochondrial-produced superoxide(O 2 ?) in the regulation of iron-regulatory hormone, hepcidin by alcohol in the liver. METHODS: For alcohol experiments, manganese superoxide dismutase knockout mice heterozygous for Sod2 gene expression(Sod2 +/) and age-matched littermate control mice(LMC), expressing Sod2 gene on both alleles, were exposed to either 10%(w/v) ethanol in the drinking water or plain water(control) for 7 d. Total cellular O 2 ? levels in hepatocytes isolated from the livers of mice were measured by electron paramagnetic resonance spectroscopy. The mitochondrial-targeted, O 2 ?-sensitive fluorogenic probe, MitoSOX Red and flow cytometry were utilized to measure O 2 ? in mitochondria. Gene and protein expression were determined by Taqman Real-time quantitative PCR and Western blotting, respectively. RESULTS: Sod2 +/- mice expressed 40% less MnSOD protein(SOD2) in hepatocytes compared to LMC mice. The deletion of Sod2 allele did not alter the basal expression level of hepcidin in the liver. 10% ethanol exposure for 1 wk inhibited hepatic hepcidin mRNA expression three-fold both in Sod2 +/ and LMC mice. O 2 ? levels in hepatocytes of untreated Sod2 +/ mice were three-fold higher than in untreated LMC mice, as observed by electron paramagnetic resonance spectroscopy. O 2 ? levels in mitochondria of Sod2 +/ mice were four-fold higher than in mitochondria of untreated LMC mice, as measured by MitoSOX Red fluorescence and flow cytometry. Alcohol induced a two-fold higher increase in O 2 ? levels in hepatocytes of LMC mice than in Sod2 +/ mice compared to respective untreated counterparts. In contrast, 1 wk alcohol exposure did not alter mitochondrial O 2 ? levels in both Sod2 +/- and control mice. CONCLUSION: Mitochondrial O2 ? is not involved in the inhibition of liver hepcidin transcription and thereby regulation of iron metabolism by alcohol. These findings also suggest that short-term alcohol consumption significantly elevates O 2 ? levels in hepatocytes, which appears not to originate from mitochondria. | Duygu Dee Harrison-Findik Sizhao Lu Emily M Zmijewski Jocelyn Jones Matthew C Zimmerman | 2013 | World Journal of Biological Chemistry2013，4，4： | 2 |
| 4 | A next-generation marker genotyping platform(AmpSeq)in heterozygous crops:a case study for marker-assisted selection in grapevine显示文摘Marker-assisted selection(MAS)is often employed in crop breeding programs to accelerate and enhance cultivar development,via selection during the juvenile phase and parental selection prior to crossing.Next-generation sequencing and its derivative technologies have been used for genome-wide molecular marker discovery.To bridge the gap between marker development and MAS implementation,this study developed a novel practical strategy with a semi-automated pipeline that incorporates trait-associated single nucleotide polymorphism marker discovery,low-cost genotyping through amplicon sequencing(AmpSeq)and decision making.The results document the development of a MAS package derived from genotyping-by-sequencing using three traits(flower sex,disease resistance and acylated anthocyanins)in grapevine breeding.The vast majority of sequence reads(⩾99%)were from the targeted regions.Across 380 individuals and up to 31 amplicons sequenced in each lane of MiSeq data,most amplicons(83 to 87%)had<10%missing data,and read depth had a median of 220–244×.Several strengths of the AmpSeq platform that make this approach of broad interest in diverse crop species include accuracy,flexibility,speed,high-throughput,low-cost and easily automated analysis. | Shanshan Yang Jonathan Fresnedo-Ramíre Minghui Wang Linda Cote Peter Schweitzer Paola Barba Elizabeth M Takacs Matthew Clark James Luby David C Manns Gavin Sacks Anna Katharine Mansfield Jason Londo Anne Fennell David Gadoury Bruce Reisch Lance Cadle-Davidson Qi Sun | 2016 | Horticulture Research2016，3，1： | 2 |
| 5 | Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial显示文摘 | Matthew T Seymour Lindsay C Thompson Harpreet S Wasan Gary Middleton Alison E Brewster Stephen F Shepherd M Sinead O’Mahony Timothy S Maughan Mahesh Parmar Ruth E Langley | 2011 | The Lancet2011，，9779： | 2 |
| 6 | Adaptation of HIV-1to human leukocyte antigen class I显示文摘 | Kawashima Y Pfafferott K Frater J Matthews P Payne R Addo M Gatanaga H Fujiwara M Hachiya A Koizumi H Kuse N Oka S Duda A Prendergast A Crawford H Leslie A Brumme Z Brumme C Allen T Brander C Kaslow R Tang J Hunter E Allen S Mulenga J Branch S Roach T John M Mallal S Ogwu A Shapiro R Prado J G Fidler S Weber J Pybus O G Klenerman P Ndung'u T Phillips R Heckerman D Harrigan P R Walker B D Takiguchi M Goulder P | 2009 | Nature2009，458，7238： | 1 |
| 7 | Mycobacteriosis in zebrafish ( Danio rerio ) research facilities 显示文摘 | Kent M L Whipps C M Matthews J L | 2004 | Comparative Biochemistry and Physiology Part C2004，138，： | 1 |
| 8 | Depletion of langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated down regulation of E-cadherin显示文摘 | MATTHEWS K LEONG C M BAXTER L | 2003 | J Virol2003，77，： | 1 |
| 9 | Functional subdivisions within anterior cingulated cortex and their relationship to autonomic nervous system function显示文摘 | Matthews S C Paulus M P Simmons A N Nelesen R A Dimsdale J E | 2004 | NeuroImage2004，22，： | 1 |
| 10 | Effects of chromium propionate on growth, carcass traits, and pork quality of growing -finishing pigs 显示文摘 | Matthews J O Guzik A C LeMieux F M | 2006 | Journal Animal Science2006，，84： | 1 |
| 11 | Work and personal life boundary management:boundary strength, work / personal life balance and the seg- mentation-integration continuum显示文摘 | Bulger C A Matthews R A Hoffman M E | 2007 | Journal of occupational Health Psychology2007，12，2： | 1 |
| 12 | Use andabuse of HOMA modeling显示文摘 | WALLACE T M LEVY J C MATTHEWS D R | 2004 | Diabetes Care2004，27，： | 1 |
| 13 | Transparent conducting Nnc oxide thin films doped with aluminum and molybdenum显示文摘 | JOEL N D TIMOTHY A G DAVID M W TERESA M B MATTHEW Y BOBBY T TIMOTHY J C | 2007 | Journal V-acuum Society Technology2007，25，4： | 1 |
| 14 | Anterior cruciate ligament reconstruction,hamstring versus bone-patellat endon-bo ne grafts:a systematic literature review of outcome from surgery显示文摘 | HERRINGTON L WRAPSON C MATTHEWS M | 2005 | Knee2005，2，1： | 1 |
| 15 | Meta-analysis of drug-in- duced adverse events associated with intensive-dose statin therapy 显示文摘 | Silva M Matthews ML Jarvls C | 2007 | Clin Ther2007，29，2： | 1 |
| 16 | Laser capture microdissection (LCM) and comparative microarray expression analysis of syncytial cells isolated from incompatible and compatible soybean (Glycine max) roots infected by soybean cyst nematode (Heterodera glycines)显示文摘 | Klink V P Overall C C Alkharouf N MacDonald M H Matthews B F | | 0，，06： | 1 |
| 17 | Rapid evolution of animal mitochondrial DNA显示文摘 | Wesley M B Matthew G JR Allen C W | 1979 | Proc Natl Acad Sci USA1979，76，4： | 1 |
| 18 | The efficacy of diazepam inenhancing motor function in children with spastic cerebralpalsy显示文摘 | Matthew A Matthew M C | 2005 | J Trop Pediatr2005，51，2： | 1 |
| 19 | Work and personal life boundary management: Boundary strength, work/personal life balance and the segmentation-integra- tion continuum显示文摘 | Bulger C A Matthews R A Hoffman M E | 2007 | Journal of Occupational Health Psy- chology2007，12，4： | 1 |
| 20 | Wild type and innate immune-deficient mice are not susceptible to the middle east respiratory syndrome eoronavirus显示文摘 | Coleman C M Matthews K L Goicochea L Frieman M B | 2014 | J Gen Virol2014，95，2： | 1 |
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