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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 | 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 |
| 3 | 凡纳滨对虾养殖塘叶绿素a与水质因子的多元回归分析显示文摘2009年4-9月期间,对上海市奉贤区某凡纳滨对虾养殖场22个养殖池塘水体叶绿素a、水温、pH、溶解氧、透明度、悬浮物(SS)、总有机碳(TOC)、五日生化需氧量(BOD5)、高锰酸盐指数(CODMn)等15项水质因子进行测定。取164组测定数据,进行描述性统计,分析叶绿素a与各项因子的相关性系数。分析结果显示,与叶绿素a呈极显著线性正相关的水质因子为SS、TOC、BOD5、CODMn、TN、TP;呈显著正相关的为DO;而叶绿素a与透明度呈极显著线性负相关,与PO43--P呈显著线性负相关;与水温、pH、NO2--N、NO3--N、NH3-N则未呈现显著相关性。根据多元线性回归选择自变量的原则,选择了TOC、TN、PO34--P和TP4项水质因子,建立了叶绿素a与4项水质因子的逐步回归模型:Chl.a=-0.0545+0.00349TOC+0.0153TN-0.418PO43--P+0.276TP(r=0.7155)。利用偏回归系数检验各水质因子对叶绿素a的影响,结果表明,对叶绿素a影响从大到小依次是TP、TOC、PO34--P和TN。研究结果对进一步探讨养殖池塘生态系统的变化规律及水环境质量保护提供了依据。 | 江敏 余根鼎 戴习林 刘利平 顾德平 胡伟国 Diana James S | 2010 | 水产学报2010，34，11： | 20 |
| 4 | 在诊断 choledochal 包囊的磁性的回声 cholangiopancreatography 的角色: 盒子系列和评论显示文摘 AIM:To determine the merits of magnetic resonance cholangiopancreatography(MRCP) as the primary diagnostic test for choledochal cysts(CC’s).METHODS:Between 2009 and 2012,patients who underwent MRCP for perioperative diagnosis were identified.Demographic information,clinical characteristics,and radiographic findings were recorded.MRCP results were compared with intraoperative findings.A PubMed search identified studies published between 1996-2012,employing MRCP as the primary preoperative imaging and comparing results with either endoscopic retrograde cholangiopancreatography(ERCP) or operative findings.Detection rates for CC’s and abnormal pancreaticobiliary junction(APBJ) were calculated.In addition detection rates for clinically related biliary pathology like choledocholithiasis and cholangiocarcinomas in patients diagnosed with CC’s were also evaluated.RESULTS:Eight patients were identified with CC’s.Six patients out of them had typeⅣCC’s,1 had type I and 1 had a new variant of choledochal cyst with confluent dilatation of the common bile duct(CBD) and cystic duct.Seven patients had an APBJ and 3 of those had a long common-channel.Gallstones were found in 2 patients,1 had a CBD stone,and 1 pancreatic-duct stone was also detected.In all cases,MRCP successfully identified the type of CC’s,as well as APBJ with ductal stones.From analyzing the literature,we found that MRCP has 96%-100% detection rate for CC’s.Additionally,we found that the range for sensitivity,specificity,and diagnostic accuracy was 53%-100%,90%-100% and 56%-100% in diagnosing APBJ.MRCP’s detection rate was 100% for choledocholithiasis and 87% for cholangiocarcinomas with concurrent CC’s.CONCLUSION:After initial ultrasound and computed tomography scan,MRCP should be the next diagnostic test in both adult and pediatric patients.ERCP should be reserved for patients where therapeutic intervention is needed. | Vikas Y Sacher James S Davis Danny Sleeman Javier Casillas | 2013 | World Journal of Radiology2013，5，8： | 15 |
| 5 | 1990—2017年中国伤害负担:2017年全球疾病负担研究结果(摘译)显示文摘伤害是全球性的公共卫生挑战,涉及各年龄组和不同性别的人群。过去三十年来,中国经济快速发展,人口老龄化趋势加重,社会呈现出城镇化、机动化和老龄化等特征。随着人们生活环境和生活方式的改变,伤害已跃居人群致死原因第五位,仅排在恶性肿瘤、心脑血管疾病、呼吸系统疾病和心肌梗死之后。据估计,中国每年在伤害方面消耗的直接医疗费用约为650亿元人民币. | 林泽婷(译) 吕来文(译) 黄晓晴(译) 李丽萍(审校) Duan Leilei Ye Pengpeng Juanita A Haagsma Jin Ye Wang Yuan Er Yuliang Deng Xiao Gao Xin Ji Cuirong Wang Linhong Marlena S Bannick W Cli Mountjoy-Venning Caitlin N Hawley Zichen Liu Mari Smith Spencer L James Theo Vos Christopher J L Murray | 2020 | 伤害医学(电子版)2020，9，2： | 15 |
| 6 | 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 |
| 7 | Calcium signaling and T-type calcium channels in cancer cell cycling显示文摘Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells, free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear; however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel isminimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers. | James T Taylor Xiang-Bin Zeng Jonathan E Pottle Kevin Lee Alun R Wang Stephenie G Yi lennifer A S Scruggs Suresh S Sikka Ming Li | 2008 | World Journal of Gastroenterology2008，14，32： | 12 |
| 8 | 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 |
| 9 | An epigenomic approach to therapy for tamoxifen-resistant breast cancer显示文摘Tamoxifen 是为雌激素受体 alpha 的前线治疗(ERα) 在绝经前的女人的积极的胸肿瘤。然而,到 tamoxifen 的抵抗发生在许多病人。嗯仍然与获得的 tamoxifen 抵抗在乳癌房间的生长起一个关键作用,建议那 ERα为治疗仍然是一个有效目标 tamoxifen 抵抗(Tam-R ) 乳癌。以识别 ERα 的新奇管理者;发信号,通过对 histone 甲基修饰词的一幅小规模的 siRNA 屏幕,我们发现了 WHSC1, histone H3K36 methyltransferase, ERα 的一个积极管理者;在乳癌房间发信号。我们证明 WHSC1 被招募到 ERα由 BET 蛋白质 BRD3/4 的基因,并且便于 ERα基因表示。小分子的赌注蛋白质禁止者 JQ1 potently 压制了经典 ERα发信号的小径和在文化的 Tam-R 乳癌房间的生长。用一个 Tam-R 乳癌异种皮移植老鼠模型,我们与 JQ1 和 ER degrader fulvestrant 由 JQ1 和联合治疗的强壮的长持续的效果在 vivo 反胸癌症活动示威了。一起拿,我们提供 epigenomic 蛋白质 BRD3/4 和 WHSC1 是雌激素受体发信号的必要管理者并且是为 Tam-R 乳癌的治疗的新奇治疗学的目标的证据。 | Qin Feng Zheng Zhang Martin J Shea Chad J Creighton Cristian Coarfa Susan G Hilsenbeck Rainer Lanz Bin He Lei Wang Xiaoyong Fu Agostina Nardone Yongcheng Song James Bradner Nicholas Mitsiades Constantine S Mitsiades C Kent Osborne Rachel Schiff Bert W O'Malley | 2014 | Cell Research2014，24，7： | 10 |
| 10 | Relationship between the exocrine and endocrine pancreas after acute pancreatitis显示文摘AIM:To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.METHODS:Relevant literature cited in three major biomedical journal databases(EMBASE,MEDLINE,and Scopus)was reviewed independently by two authors.There were no language constraints but the search was limited to human studies.Studies included were cohort studies of adult patients who were discharged after an attack of acute pancreatitis.Patients were excluded if they were under 18 years of age or had a previous diagnosis of prediabetes or diabetes mellitus,pancreatic exocrine insufficiency,or chronic pancreatitis.The main outcome measure was the prevalence of concomitant pancreatic exocrine insufficiency in patients who were diagnosed with prediabetes and diabetes mellitus after an attack of acute pancreatitis.Subgroup analysis was conducted for patients who were diagnosed with prediabetes only and those who were diagnosed withdiabetes mellitus only.Subgroup analysis looking at the time course of concomitant pancreatic exocrine and endocrine insufficiency was also conducted.Pooled prevalence and corresponding 95%confidence intervals were calculated for all outcome measures and P-values<0.05 were deemed statistically significant.RESULTS:Eight clinical studies comprising of 234patients met all eligibility criteria.The pooled prevalence of newly diagnosed prediabetes or diabetes in individuals after acute pancreatitis was 43%(95%CI:30%-56%).The pooled prevalence of pancreatic exocrine insufficiency in individuals after acute pancreatitis was 29%(95%CI:19%-39%).The prevalence of concomitant pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes was 40%(95%CI:25%-55%).The prevalence of concomitant pancreatic exocrine insufficiency among individuals with prediabetes alone and diabetes mellitus alone was 41%(95%CI:12%-75%)and 39%(95%CI:28%-51%),respectively.Further analysis showed that the prevalence of concomitant pancreatic exocrine insufficiency in individuals with prediabetes or diabetes decreases over time after an attack of acute pancreatitis.CONCLUSION:Pancreatic exocrine insufficiency occurs in 40%of individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.Further studies are needed to investigate the pathogenesis of diabetes in this setting. | Stephanie L M Das James I C Kennedy Rinki Murphy Anthony R J Phillips John A Windsor Maxim S Petrov | 2014 | World Journal of Gastroenterology2014，20，45： | 9 |
| 11 | 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 |
| 12 | Degenerative meniscus: Pathogenesis, diagnosis, and treatment options显示文摘The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than onethird of the adult meniscus, healing potential in the setting of chronic degeneration remains low. Continued hoop and shear stresses upon the degenerative meniscus results in gross failure, often in the form of complex tears in the posterior horn and midbody. Patient history and physical examination are critical to determine the true source of pain, particularly with the significant incidence of simultaneous articular pathology. Joint line tenderness, a positive Mc Murray test, and mechanical catching or locking can be highly suggestive of a meniscal source of knee pain and dysfunction. Radiographs and magnetic resonance imaging are frequently utilized to examine for osteoarthritis and to verify the presence of meniscal tears, in addition to ruling out other sources of pain. Non-operative therapy focused on nonsteroidal anti-inflammatory drugs and physical therapy may be able to provide pain relief as well as improve mechanical function of the knee joint. For patients re-fractory to conservative therapy, arthroscopic partial meniscectomy can provide short-term gains regarding pain relief, especially when combined with an effective, regular physiotherapy program. Patients with clear mechanical symptoms and meniscal pathology may benefit from arthroscopic partial meniscectomy, but surgery is not a guaranteed success, especially with concomitant articular pathology. Ultimately, the long-term outcomes of either treatment arm provide similar results for most patients. Further study is needed regarding the short and long-term outcomes regarding conservative and surgical therapy, with a particular focus on the economic impact of treatment as well. | Richard Howell Neil S Kumar Nimit Patel James Tom | 2014 | World Journal of Orthopedics2014，5，5： | 8 |
| 13 | European evidence based consensus for endoscopy in inflammatory bowel disease显示文摘 | Vito Annese Marco Daperno Matthew D. Rutter Aurelien Amiot Peter Bossuyt James East Marc Ferrante Martin G?tz Konstantinos H. Katsanos Ralf Kie?lich Ingrid Ordás Alessandro Repici Bruno Rosa Shaji Sebastian Torsten Kucharzik Rami Eliakim | 2013 | Journal of Crohn’s and Colitis2013，，12： | 7 |
| 14 | 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 |
| 15 | Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice显示文摘BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments. AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD. METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD)(14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice. CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients. | Kandy T Velázquez Reilly T Enos Jackie E Bader Alexander T Sougiannis Meredith S Carson Ioulia Chatzistamou James A Carson Prakash S Nagarkatti Mitzi Nagarkatti E Angela Murphy | 2019 | World Journal of Hepatology2019，11，8： | 6 |
| 16 | 土壤中的生物多样性与生态系统功能显示文摘我们回顾了目前关于土壤生物多样性及其在生态系统过程中的作用、对于人类目标的重要性及对胁迫和扰动的恢复能力等的研究进展。现存物种的数量远远大于人们已经描述的数量,即使是对于肉眼可见的分类群也是如此。而且也普遍缺乏在生物地理学上的综合描述。迫切需要在分类学和对新一代系统科学家培训上做更大努力。尤其是应当集中致力于就我们所知。对生态系统功能起关键作用的土壤生物类群方面。为了确定这种类群,需要对土壤生物区系的影响圈(sphere of Influence,SOI),如根的生物区系、有机物质破碎者(shredder)和土壤生物扰动者(bioturbator)加以识别,这些影响圈比如可能通过与植物的相互作用而控制着生态系统的过程。在这些SOI中,我们分析出了土壤有机体的功能类群。最迫切需要研究的问题是将物种按功能类群进行区分,并确定功能类群中的物种冗余。这种迫切性是根据为阐述与集约化农业、森林扰动、环境污染和全球环境变化有关的土壤功能丧失程度的需要而确定的。目前认为最处于危险的土壤生物区系是那些大型动物群的有机物破碎者、土壤生物扰动者、某些专门的细菌(如硝化细菌和固氮菌)以及形成真菌的菌根中贫乏物种的功能类群。在开展这些优先性研究时,需要使用长期的和大尺度的田间试验,以及地理统计学和地理信息系统等现代方法进行试验研究。 | Lijbert Brussaard Val M.Behan-Pelletier David E.Bignell Valerie K.Brown Wim Didden Patrica Folgarait Carlos Fragoso Diana Wall Freckman Vadakattu V.S.R.Gupta Tsutomu Hattori's David L.Hawkworth Carole Klopatek Patric Lavelle David W.Malloch Josef Rusek Bengt Sderstrom James M.Tiedje Ross A.Virginia 闵庆文 | 1997 | 人类环境杂志1997，26，8： | 6 |
| 17 | 血压变异性预测自发性脑出血患者的院内不良预后显示文摘越来越多的证据表明,较高的收缩压变异性(systolicblood pressure variability ,SBPV)可能与脑出血患者的不良预后相关。该研究探讨了 SB PV 与院内脑出血预后之间的关系。研究者在2个医疗系统中收集了10年的自发性脑出血患者的连续数据。记录人口统计学、病史、实验室测试、计算机断层扫描数据、院内治疗情况以及神经和功能评估。在入院后24h内获取血压记录。 | 刘青 叶鹏 Divani AA Liu X Di Napoli M Lattanzi S Ziai W James ML Jafarli A Jafari M Saver JL Hemphill JC Vespa PM Mayer SA Petersen A | 2019 | 中华高血压杂志2019，27，8： | 6 |
| 18 | Reduced Exposure to Calcineurin Inhibitors Early After Liver Transplantation Prevents Recurrence of Hepatocellular Carcinoma显示文摘 | Manuel Rodríguez-Perálvarez Emmanuel Tsochatzis María Carmen Naveas Giulia Pieri Carmen García-Caparrós James O’Beirne Antonio Poyato-González Gustavo Ferrín-Sánchez Jose Luis Montero-álvarez David Patch Douglas Thorburn Javier Brice?o Manuel De la Mata A | 2013 | Journal of Hepatology2013，，： | 5 |
| 19 | Tumor Antigen Specific Activation of Primary Human T-Cells Expressing a Virally Encoded Chimeric T-Cell Receptor Specific for p185HER2显示文摘We have developed and tested chimeric T-cell receptors (TCR) specific for p185HER2. In these experiments, retroviral vectors expressing the N29γ or N29ζ receptors were constructed in pRET6. Amphotropic viral producer cells were established in the GALV-based PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes (PBL) were virally transduced using an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies, followed by viral infection in the presence of fibronectin fragment CH296. Transduced cells were co-cultured with human tumor cell lines that overexpress (SK-OV-3) or underexpress (MCF7) p185HER2 to assay for antigen specific im- mune responses. Both CM+ and CD8+ T-cells transduced with the N29γ or N29ζ chTCR demonstrated HER2-specific anti- gen responses, as determined by release of Th1 like cytokines, and cellular cytotoxicity assays. Our results support the fea- sibility of adoptive immunotherapy with genetically modified T-cells expressing a chTCR specific for p185HER2. | 杨建民 Michael S FRIEDMAN Christopher M REYNOLDS Marianne T HUBEN Lee WILKE Jennifer FULLER 李桥 Zelig ESHHAR James J MULE Kevin T MCDONAGH | 2004 | Journal of Microbiology and Immunology2004，2，4： | 5 |
| 20 | 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 |
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