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| 1 | 煤型稀有金属矿床:成因类型、赋存状态和利用评价显示文摘煤和含煤岩系中稀有金属元素的研究,是当今煤地质学研究的热点问题之一。煤和含煤岩系中高度富集并可以开发利用的稀有金属元素包括锂、钪、钛、钒、镓、锗、硒、锆、铌、铪、钽、铀、稀土元素(包括镧系元素和钇)、贵金属元素等。以煤-锗、煤-镓、煤-铀、煤-铌、煤-稀土元素等煤型稀有金属矿床为例,论述了这些矿床的地质成因、赋存状态和利用评价方法。煤型稀有金属矿床的研究,不仅对研究煤层的地质成因、煤层对比、含煤盆地形成与后期改造、区域地质历史演化和突发地质事件可以提供重要的煤地球化学和煤矿物学证据,而且对煤炭经济循环发展、煤炭利用过程中环境保护,以及对国家稀有金属资源安全也具有重要的现实和社会意义。 | 代世峰 任徳贻 周义平 Vladimir VSeredin 李大华 张名泉 James C Hower Colin R Ward 王西勃 赵蕾 宋晓林 | 2014 | 煤炭学报2014，39，8： | 111 |
| 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 | Contribution of oxidative stress to pulmonary arterial hypertension显示文摘Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure. | Vincent G DeMarco Adam T Whaley-Connell James R Sowers Javad Habibi Kevin C Dellsperger | 2010 | World Journal of Cardiology2010，2，10： | 21 |
| 4 | Sleep,immunity and inflammation in gastrointestinal disorders显示文摘Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients. | Tauseef Ali James Choe Ahmed Awab Theodore L Wagener William C Orr | 2013 | World Journal of Gastroenterology2013，19，48： | 15 |
| 5 | miR-182参与调节胶质母细胞瘤的凋亡、生长和分化(英文)显示文摘Glioblastoma multiforme(GBM)is a lethal,therapy-resistant brain cancer consisting of numerous tumor cell subpopulations,including stem-like glioma-initiating cells(GICs),which contribute to tumor recurrence following initial response to therapy.Here,we identified miR-182 as a regulator of apoptosis,growth,and differentiation programs whose expression level is correlated with GBM patient survival.Repression of Bcl2-like12(Bcl2L12),c-Met,and hypoxia-inducible factor 2α(HIF2A)is of central importance to miR-182 anti-tumor activity,as it results in enhanced therapy susceptibility,decreased GIC sphere size,expansion,and stemness in vitro.To evaluate the tumor-suppressive function of miR-182 in vivo,we synthesized miR-182-based spherical nucleic acids(182-SNAs);i.e.,gold nanoparticles covalently functionalized with mature miR-182 duplexes.Intravenously administered 182-SNAs penetrated the bloodbrain/blood-tumor barriers(BBB/BTB)in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma,causing reduced tumor burden and increased animal survival.Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM. | Kouri FM Hurley LA Daniel WL Day ES Hua Y Hao L Peng CY Merkel TJ Queisser MA Ritner C Zhang H James CD Sznajder JI Chin L Giljohann DA Kessler JA Peter ME Mirkin CA Stegh AH | 2015 | 中华神经外科疾病研究杂志2015，14，2： | 14 |
| 6 | 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 |
| 7 | 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 |
| 8 | Progress in structural materials for aerospace systems 1 1 The Golden Jubilee Issue—Selected topics in Materials Science and Engineering: Past, Present and Future, edited by S. Suresh.显示文摘 | James C Williams Edgar A Starke | 2003 | Acta Materialia2003，，19： | 7 |
| 9 | 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 |
| 10 | Murine lung eosinophil activation and chemokine production in allergic airway inflammation显示文摘Eosinophils play important roles in asthma and lung infections.Murine models are widely used for assessing the functional significance and mechanistic basis for eosinophil involvements in these diseases.However,little is known about tissue eosinophils in homeostasis.In addition,little data on eosinophil chemokine production during allergic airway inflammation are available.In this study,the properties and functions of homeostatic and activated eosinophils were compared.Eosinophils from normal tissues expressed costimulation and adhesion molecules B7-1,B7-2 and ICAM-1 for Ag presentation but little major histocompatibility complex(MHC)class II,and were found to be poor stimulators of T-cell proliferation.However,these eosinophils expressed high levels of chemokine mRNA including C10,macrophage inflammatory protein(MIP)-1a,MIP-1c,MIP-2,eotaxin and monocyte chemoattractant protein-5(MCP-5),and produced chemokine proteins.Eosinophil intracellular chemokines decreased rapidly with concomitant surface marker downregulation upon in vitro culturing consistent with piecemeal degranulation.Lung eosinophils from mice with induced allergic airway inflammation exhibited increased chemokines mRNA expression and chemokines protein production and upregulated MHC class II and CD11c expression.They were also found to be the predominant producers of the CCR1 ligands CCL6/C10 and CCL9/MIP-1c in inflamed lungs.Eosinophil production of C10 and MIP-1c correlated with the marked influx of CD11bhigh lung dendritic cells during allergic airway inflammation and the high expression of CCR1 on these dendritic cells(DCs).The study provided baseline information on tissue eosinophils,documented the upregulation of activation markers and chemokine production in activated eosinophils,and indicated that eosinophils were a key chemokine-producing cell type in allergic lung inflammation. | C Edward Rose Jr Joanne A Lannigan Paul Kim James J Lee Shu Man Fu Sun-sang J Sung | 2010 | Cellular & Molecular Immunology2010，7，5： | 6 |
| 11 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 12 | 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 |
| 13 | 睾酮缺乏症的诊断和治疗显示文摘近些年来,随着睾酮缺乏症(TD)发病率的上升、新药的不断开发、以及商业推广的深入,睾酮替代疗法(TST)的临床应用显著增多。然而,关于睾酮缺乏症的诊断标准以及TST的应用和监测,仍然不是很明确。此种现象主要源于睾酮的多重作用靶点。在人体内,睾酮参与了很多生理过程的调节,同时睾酮的表达水平也受很多疾病及药物的影响。因此,睾酮缺乏症的临床症状和体征具有多样性和非特异性,也就增加了睾酮缺乏症的诊断难度,尤其在老年人群中。临床上,关于血清睾酮水平的检测也存在争议,不同实验室之间存在一定的差异,因此也很难界定睾酮水平的诊断标准。很多医学专业组织试图制定睾酮缺乏症的诊断指南,但彼此间很难达成统一。另外,临床使用的睾酮制剂也层出不穷,相应的TST治疗方案也像TD的诊断标准一样不断更新和变化。临床上,随着TST的不断推进,专科医师必须不断更新对于TD和HTST的了解和治疗及应用。本文旨在阐述TD的最新概念及其诊断和治疗的新进展。 | James A McBride Culley C Carson Robert M Coward | 2015 | Asian Journal of Andrology2015，17，2： | 5 |
| 14 | Sensitivity and inter-observer variability for capsule endoscopy image analysis in a cohort of novice readers显示文摘瞄准:为检测囊内视镜检查法调查结果决定新手阅读器(第 4 个年医学院的学生) 的性能。方法:小肠损害的十个囊内视镜检查法盒子予读者被以。标准答案调查结果被胃的肠学预先规定。十个标准答案“目标”在 10 个盒子之中被识别。读者们被给快速的读者软件的 30-min 概述并且指示标记畸形的任何潜在的区域。一个软件程序用 SAS 被开发分析缩小的调查结果。结果:为检测标准答案调查结果的全面敏感是 80% 。作为一个组,至少 5 从 10 个读者检测了每记录发现的每个标准答案。当读者的结果被联合时,所有标准答案目标被识别。偶然的 finding/false 积极的率每读者在 8.2-59.8 之间变化了。结论:有最小的内视镜的经验的医学院的学生的一块面板能在在囊内视镜检查法上检测损害完成高敏感。一组新手读者能预先屏蔽为进一步的评论缩小小肠损害的潜在的区域的记录。这些指图必须被考察决定临床的关联。进一步的研究是进行中的估计另外的队。 | Gary C Chen Pedram Enayati Tam Tran Mary Lee-Henderson Clifford Quan Gareth Dulai Ian Arnott James Sul Rome Jutabha | 2006 | World Journal of Gastroenterology2006，12，8： | 5 |
| 15 | 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 |
| 16 | 与青年医师谈科研工作的起步显示文摘 | James C Thompson 张俊 林言箴 | 2000 | 外科理论与实践2000，5，2： | 4 |
| 17 | Nat Med:靶向两分子或有助于彻底治愈白血病显示文摘科学家在癌细胞内发现两个信号蛋白能够让癌细胞抵抗化疗。研究表明阻断这两种蛋白能够增强化疗对人类白血病小鼠模型的治疗效果。相关研究结果发表在国际学术期刊NatureMedicine上。研究人员发现在治疗中阻断c-Fos和Dusp1这两个蛋白能够治愈一些受激酶驱动且抵抗治疗的白血病和实体瘤。 | Meenu Kesarwani, Zachary Kincaid, Ahmed Gomaa, Erika Huber, Sara Rohrabaugh, Zain Siddiqui, Muhammad F Bouso, Kakajan Komurov, James C Mulloy, Jose A Cancelas, H Leighton Grimes Mohammad Azam Tahir Latif Ming Xu H Leighton Grimes Mohammad Azam | 2017 | 现代生物医学进展2017，17，17： | 4 |
| 18 | Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice显示文摘Epigenetic 基因规定畸形包括精神分裂症和消沉在各种各样的 neuropsychiatric 混乱,以及在心情和焦虑的规定被含有。另外, epigenetic 机制涉及精神病学的药的行动。当前的 anxiolytic 药有新药的重要缺点,和开发被保证。二蛋白质, G9a (也作为 EHMT2 或 KMT1C 知道) 并且 GLP (象 G9a 一样蛋白质,也作为 EHMT1 或 KMT1D 知道) ,它甲醇化物离氨酸 9 histone H3 (H3K9 ) ,能正在答应 anxiolytic 目标。G9a 的出生后的基因大美人减少焦虑相关的行为,与由过去常对待焦虑(amitriptyline, imipramine 和 paroxetine ) 的一些药的 G9a 层次的减小一致。相反地,在有 GLP haplodeficiency 的老鼠有增加的像焦虑的行为。我们寻求了决定是否 G9a/GLP, UNC0642 和 A-366 的二个药理学禁止者,将有类似的效果到基因 G9a/GLP 不足。当予成年老鼠以时,我们发现有任何一个化合物的 G9a/GLP 抑制减少了像焦虑的行为,与在大脑的减少的 H3K9 methylation 一起。相反,到这些的暴露从胚胎的白天加重(E9.5 ) 9.5 增加了像焦虑的行为直到出生并且减少在成人生活的社会相互作用,当 H3K9 methylation 在在成年老鼠的大脑的正常层次时。这些调查结果增强 G9a/GLP 在大脑开发的不同阶段在像焦虑的行为上有不同效果的基因证据,并且建议指向这条 histone methyltransferase 小径能为开发新 anxiolytic 药是有用的。这些数据也建议在 utero 的抗抑郁剂暴露能在成人生活有否定效果,并且这些效果的进一步的调查被保证。 | Dong-yao WANG Joel KOSOWAN James SAMSOM Laura LEUNG Kai-lai ZHANG Ying-xiang LI Yan XIONG Jian JIN Arturas PETRONIS Gabriel OH Albert H C WONG | 2018 | Acta Pharmacologica Sinica2018，39，5： | 4 |
| 19 | Cervical inlet patch-optical coherence tomography imaging and clinical significance显示文摘AIM:To demonstrate the feasibility of optical coherence tomography(OCT)imaging in differentiating cervical inlet patch(CIP)from normal esophagus,Barrett'sesophagus(BE),normal stomach and duodenum. METHODS:This study was conducted at the Veterans Affairs Boston Healthcare System(VABHS).Patients undergoing standard esophagogastroduodenoscopy at VABHS,including one patient with CIP,one representative patient with BE and three representative normal subjects were included.White light video endoscopy was performed and endoscopic 3D-OCT images were obtained in each patient using a prototype OCT system.The OCT imaging probe passes through the working channel of the endoscope to enable simultaneous video endoscopy and 3D-OCT examination of the human gastrointestinal(GI)tract.Standard hematoxylin and eosin(H and E)histology was performed on biopsy or endoscopic mucosal resection specimens in order to compare and validate the 3D-OCT data. RESULTS:CIP was observed from a 68-year old male with gastroesophageal reflux disease.The CIP region appeared as a pink circular lesion in the upper esophagus under white light endoscopy.OCT imaging over the CIP region showed columnar epithelium structure,which clearly contrasted the squamous epithelium structure from adjacent normal esophagus.3D-OCT images obtained from other representative patients demonstrated distinctive patterns of the normal esophagus,BE,normal stomach,and normal duodenum bulb.Microstructures,such as squamous epithelium,lamina propria, muscularis mucosa,muscularis propria,esophageal glands,Barrett's glands,gastric mucosa,gastric glands, and intestinal mucosal villi were clearly observed with OCT and matched with H and E histology.These results demonstrated the feasibility of using OCT to evaluate GI tissue morphology in situ and in real-time. CONCLUSION:We demonstrate in situ evaluation of CIP microstructures using 3D-OCT,which may be a useful tool for future diagnosis and follow-up of patients with CIP. | Chao Zhou Tejas Kirtane Tsung-Han Tsai Hsiang-Chieh Lee Desmond C Adler Joseph M Schmitt Qin Huang James G Fujimoto Hiroshi Mashimo | 2012 | World Journal of Gastroenterology2012，18，20： | 3 |
| 20 | A/E大肠杆菌疫苗动物模型的建立显示文摘致病性和出血性大肠杆菌 (代表株 EPEC E2 34 8和 EHEC O15 7)是婴幼儿腹泻、出血性结肠炎和尿路感染综合征 (尿毒症 )的主要病原菌 ,它们同属于粘附脱落 (Attaching/ Effacing,A/ E)大肠杆菌群 ,具有许多共同的毒力基因 ,定位于致病岛 L EE(the locus of enterocyte effacement)上。本试验主要就 A/ E大肠杆菌致病岛 L EE的 2个主要调节基因 lux和 ler基因对细菌致病性和免疫原性的影响进行了研究。所使用的始发菌株为兔致病性大肠杆菌 RDEC- 1,根据同源重组的原理 ,利用自杀性载体 p CVD44 2技术 ,敲除了位于染色体上的 lux和 ler基因 ,构建了 lux和 ler基因缺失突变株 ,研究了这 2个基因对细菌生长、毒力因子表达的调控作用以及基因缺失突变株的致病性和免疫保护作用。家兔实验研究表明 ,lux基因缺失突变株仍然残存着部分致病作用 ,不足以成为理想的致弱疫苗 ;而 ler基因缺失突变株安全性好 ,具有良好的免疫保护作用 ,是理想的家兔致弱疫苗候选株。这些研究资料为人 A/ E大肠杆菌疫苗 ,尤其是 EHEC O15 7疫苗的研制指明了方向 ,并提供了技术路线。 | 冯书章 Edgar C Boedeker Chengru Zhu Timothy Thate James Kaper 朱平 邓定华 | 2002 | 中国兽医学报2002，22，6： | 3 |
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