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| 1 | The roles of MAPKs in disease显示文摘印射响应许多 ligands 和房间刺激涉及大量的细胞的小径和功能的家族 ases transduce 信号。MAPK 的异常或不恰当的功能现在在从癌症到煽动性的疾病到肥胖和糖尿病的疾病被识别了。在许多房间类型, MAPK ERK1/2 被连接到细胞增殖。因为在地岬和 B-Raf 的变化,能激活 ERK1/2 串联,在许多人的肿瘤被发现, ERK1/2 被认为在一些癌症起一个作用。发信号的反常 ERK1/2 也在 polycystic 肾疾病被发现了,并且象 cardio-facio-cutaneous 症候群那样的严肃的发展混乱在 ERK1/2 串联的部件从变化产生。ERK1/2 在区分得好的房间是必要的并且在神经原并且在上皮的极性的维护被连接了到长期的 potentiation。另外, ERK1/2 为在胰腺的贝它房间的胰岛素基因抄写是重要的,它响应传播葡萄糖的增加生产胰岛素在有机体允许有效葡萄糖利用和存储。导致或镇压的营养素和荷尔蒙胰岛素分泌物以在贝它房间上反映能分泌的需求的一种方式激活或禁止 ERK1/2。在这和另外的规章的小径的骚乱可以导致对某些人的混乱的病原学的 ERK1/2 的贡献。 | Michael C Lawrence Arif Jivan Chunli Shao Lingling Duan Daryl Goad Elma Zaganjor Jihan Osborne Kathleen McGlynn Steve Stippec Svetlana Earnest Wei Chen Melanie H Cobb | 2008 | Cell Research2008，18，4： | 64 |
| 2 | 卫生经济学评价报告标准共识2022(CHEERS 2022):卫生经济学评价报告指导意见更新版显示文摘卫生经济学评价是对备选行动方案的成本和结果的比较分析。2013年发表的《卫生经济学评价报告标准共识》(CHEERS)提出了卫生经济学评价的特点,确保结果正确阐释,以支持决策制订。2013版CHEERS旨在指导研究报告撰写者准确报告卫生干预和对照措施、背景、过程、结果等评价细节,使审稿人理解文章内容,帮助读者使用研究结果。本版共识将取代2013版共识,其更加适用于各类卫生经济学评价,结合学科发展和方法更新的需要,更注重患者、公众等相关利益方的参与。本共识适用多种个体或人群健康干预措施(简单或复杂)在不同政策场景的应用分析,包括医疗服务、公共卫生、教育、社会服务等。本文概要介绍了CHEERS 2022共识中包含的28个检查项及每一个检查项的相关建议。CHEERS 2022共识主要用于指导研究人员撰写拟投递同行评议学术期刊的卫生经济学评价文章,亦可用于期刊编辑和审稿专家对待发表文章的评价。熟悉了解本共识要求,还有助于研究人员规划评价研究。随着决策透明度要求提高,本共识可支持卫生技术评估机构建立评价报告标准。 | Don Husereau Michael Drummond Federico Augustovski Esther de Bekker-Grob Andrew H Briggs Chris Carswell Lisa Caulley Nathorn Chaiyakunapruk Dan Greenberg Elizabeth Loder Josephine Mauskopf C Daniel Mullins Stavros Petrou Raoh-Fang Pwu Sophie Staniszewska on behalf of CHEERSISPOR Good Research Practices Task Force 肖月(译) 邱英鹏(译) 史黎炜(译) 张治国(译) 张歆(译) 王海银(译) 翟铁民(译) | 2022 | 英国医学杂志中文版2022，25，8： | 31 |
| 3 | Vascular invasion in pancreatic cancer:Imaging modalities,preoperative diagnosis and surgical management显示文摘Pancreatic cancer is associated with a poor prognosis,and surgical resection remains the only chance for curative therapy.In the absence of metastatic disease,which would preclude resection,assessment of vascular invasion is an important parameter for determining resectability of pancreatic cancer.A frequent error is to misdiagnose an involved major vessel.Obviously,surgical exploration with pathological examination remains the'gold standard'in terms of evaluation of resectability,especially from the point of view of vascular involvement.However,current imaging modalities have improved and allow detection of vascular invasion with more accuracy.A venous resection in pancreatic cancer is a feasible technique and relatively reliable.Nevertheless,a survival benefit is not achieved by curative resection in patients with pancreatic cancer and vascular invasion.Although the discovery of an arterial invasion during the operation might require an aggressive management,discovery before the operation should be considered as a contraindication.Detection of vascular invasion remains one of the most important challenges in pancreatic surgery.The aim of this article is to provide a complete review of the different imaging modalities in the detection of vascular invasion in pancreatic cancer. | Nicolas C Buchs Michael Chilcott Pierre-Alexandre Poletti Leo H Buhler Philippe Morel | 2010 | World Journal of Gastroenterology2010，16，7： | 29 |
| 4 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 5 | Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: A systematic review and meta analysis显示文摘AIM: To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs.METHODS: Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS: Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95%CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95%CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95%CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95%CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95%CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendall's tau value of 0.31 (P = 0.16), indication no publication bias. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs. | Srinivas R Puli Nikhil Kalva Matthew L Bechtold Smitha R Pamulaparthy Micheal D Cashman Norman C Estes Richard H Pearl Fritz-Henry Volmar Sonu Dillon Michael F Shekleton David Forcione | 2013 | World Journal of Gastroenterology2013，19，23： | 14 |
| 6 | Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)显示文摘Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult tissues.At least 14 BMPs have been identified in mammals.Different BMPs exert distinct but overlapping biological functions.Through a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs.Nonetheless,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated.Here,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs.Hierarchical clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 cluster.We also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase pathway.Furthermore,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR pathways.While the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs. | Linghuan Zhang Qing Luo Yi Shu Zongyue Zeng Bo Huang Yixiao Feng Bo Zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*Lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang | 2019 | Genes & Diseases2019，6，3： | 11 |
| 7 | Significant association between ABO blood group and pancreatic cancer显示文摘AIM:To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the blood donor database from our local blood bank (Central Blood Bank),and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh,Pennsylvania,we identified 274 pancreatic cancer patients with previously determined serological ABO blood group information.The ABO blood group frequency was compared between these patients and 708842 individual,community-based blood donors who had made donations to Pittsburgh's Central Blood Bank between 1979 and 2009.RESULTS:The frequency of blood group A was statistically significantly higher amongst pancreatic cancer patients compared to its frequency amongst the regional blood donors [47.63% vs 39.10%,odds ratio (OR)=1.43,P=0.004].Conversely,the frequency of blood group O was significantly lower amongst pancreatic cancer patients relative to the community blood donors (32.12% vs 43.99%,OR=0.60,P=0.00007).There were limited blood group B (n=38) and AB (n=17) pancreatic cancer patients;the overall P trend value comparing patient to donor blood groups was 0.001.CONCLUSION:The ABO blood group is associated with pancreatic cancer risk.Future studies should examine the mechanism linking pancreatic cancer risk to ABO blood group. | Julia B Greer Mark H Yazer Jay S Raval M Michael Barmada Randall E Brand David C Whitcomb | 2010 | World Journal of Gastroenterology2010，16，44： | 10 |
| 8 | 钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。 | Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无 郭鹤鸣(译) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 9 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 10 | Microscopic colitis:A large retrospective analysis from a health maintenance organization experience显示文摘AIM:To examine the demographic data on a large multi-ethnic population of patients with microscopic colitis (MC) in Southern California and to determine the association of MC with inflammatory bowel disease (IBD) and colorectal cancer.METHODS: All patients diagnosed with MC by colonic biopsy from 1996-2005 were identified utilizing a pathology database. All biopsies were reviewed by experienced pathologists utilizing standard histologic criteria. Patients' medical records were reviewed and data regarding patient age, co-morbidities, sex, ethnicity, and medications were analyzed. An age-and sexmatched standard control group was also generated. Chi-square test was used to evaluate the associations of co-morbidities between lymphocytic colitis (LC), collagenous colitis (CC) and the control group.RESULTS: A total of 547 cases of MC were identif ied,376 patients with LC and 171 patients with CC. The female/male ratio was 3:1 in CC and 2.7:1 in LC patients. Celiac disease (P<0.001), irritable bowel syndrome (IBS) (P<0.001), and thyroid diseases (P<0.001) were found to have a higher occurrence in MC compared to the control group. No statistical differences in the occurrence of colorectal cancer, diabetes and IBD were found between the MC group and the control group.CONCLUSION: This is the largest group of patients with MC known to the authors that has been studied to date. Conditions such as celiac disease, IBS, and thyroid diseases were found to be related to MC. Furthermore, neither an increased risk of colorectal cancer nor IBD was associated with MC in this study. | Kevin T Kao Benito A Pedraza Amy C McClune David A Rios Yi-Qiong Mao Robert H Zuch Michael H Kanter Sony Wirio Chris N Conteas | 2009 | World Journal of Gastroenterology2009，15，25： | 5 |
| 11 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 12 | Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies显示文摘在地岬基因的 Oncogenic 变化在人的癌症是很普通的,导致有描绘得好的选择优点,而且不太听说得好的危险的房间。我们执行了一幅大规模 loss-of-function 屏幕识别被转变 KRAS 的结肠癌房间,然而并非由缺乏这 oncogene 的衍生物要求的基因。最高得分的基因然后在 KRAS 变异、野类型的癌症房间的一块更大的面板被测试。表示 oncogenic KRAS 的癌症房间被发现高度依赖于抄写因素 GATA2 和 DNA 复制开始管理者 CDC6。与已知的目标用许多药扩大这分析,我们发现有变异的 KRAS 的癌症房间与 topoisomerase 抑制显示出选择嗜好到 proteasome 功能,以及合成致命性。联合指向引起的这些功能改善了相对野类型的房间 KRAS 变异的房间杀死。这些观察建议新奇目标和在地岬变异的癌症为最佳的效果联合存在治疗的新方法,它传统地被看作对治疗高度倔强。 | Michael Steckel Miriam Molina-Arcas Britta Weigelt Michaela Marani Patricia H Warne Hanna Kuznetsov Gavin Kelly Becky Saunders Michael Howell Julian Downward David C Hancock | 2012 | Cell Research2012，22，8： | 5 |
| 13 | Status review of mercury control options for coal-fired power plants显示文摘 | John H Pavlish Everett A Sondreal Michael D Mann Edwin S Olson Kevin C Galbreath Dennis L Laudal Steven A Benson | 2003 | Fuel Processing Technology2003，，2： | 4 |
| 14 | 染料敏化分解水制氢技术进展显示文摘介绍了染料敏化分解水制氢的基本原理。综述了染料分子的选取,使用氧化还原调节剂的机理和研究进展。指出染料分子对光谱的吸收特性,激发态染料分子能级与半导体导带的相对位置,染料分子与半导体的吸附情况,表面键合强度直接影响对光子的吸收,电子的注入,从而影响产氢量。此外,I-/I3-作为氧化还原调节剂可有效还原染料分子,实现持续产氢。最后提出了染料敏化分解水制氢的间歇式反应器结构,以及通过选择用于敏化的半导体来提高产氢率的思路。 | 倪萌 LEUNG MICHAEL K H LEUNG DENNIS Y C | 2006 | 电源技术2006，30，10： | 3 |
| 15 | p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival显示文摘响应 DNA 损坏的房间命运的中央仲裁人是 p53,它调整涉及房间周期拘捕,幸存和 apoptosis 的基因的表示。尽管 DNA 损坏开始的许多回答被描绘了,肌动朊细胞骨架管理者的角色大部分是未知的。我们现在显示出那 RhoC 和秘鲁利玛机场之代号 kinase (LIMK2 ) 2 是 genotoxic 代理人导致的直接 p53 目标基因。尽管 RhoC 和 LIMK2 在肌动朊细胞骨架规定有生长得很好的角色,我们的结果显示 LIMK2 的激活也有支持幸存的功能追随者 DNA 损坏。由调停 siRNA 的击倒或选择的药理学封锁的 LIMK 抑制敏化房间到无线电 -- 或化疗,以便当与 LIMK 抑制结合了时,当单身地管理了时,是尚不致命的治疗导致了房间死亡。我们的调查结果建议把 LIMK 禁止者与 genotoxic 治疗相结合能比单个代理人的管理更有效,并且加亮在肌动朊细胞骨架管理者和 DNA 之间的一个新奇连接导致损坏的房间幸存机制。 | Daniel R Croft Diane Crighton Michael S Samuel Filipe C Lourenco June Munro Jenifer Wood Karim Bensaad Karen H Vousden Owen J Sansom Kevin M Ryan Michael F Olson | 2011 | Cell Research2011，21，4： | 3 |
| 16 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 17 | Degradation Mechanisms of Vertical Cavity Surface Emitting Lasers, Quantum Electronics显示文摘 | Michael C Y Robert W H Pierre M P | 1996 | IEEE Journal1996，32，： | 2 |
| 18 | Varied Line-space Gratings: Past, Present and Future显示文摘 | MICHAEL C H | 1985 | SPIE1985，560，： | 2 |
| 19 | Employee performance cues in a hotel service environment: influence on perceived service quality, value, and word-of-mouth intentions显示文摘 | Michael D H Keith C J | 1996 | Journal of Business Research1996，35，6： | 1 |
| 20 | Stonecutters Bridge-Durability,Maintenance and Safety Considerations显示文摘 | Michael C H Hui Chris K P Wong | 2009 | Structure and Infrastructure Engineering2009，5，3： | 1 |
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