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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 | Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer显示文摘Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer (HCC). Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors ('small molecule inhibitors') and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin (mTOR) upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation. mTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account. | Michael Hpfner Detlef Schuppan Hans Scherübl | 2008 | World Journal of Gastroenterology2008，14，1： | 33 |
| 3 | 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 |
| 4 | 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 |
| 5 | 2018加拿大心境障碍与焦虑障碍治疗协作组/国际双相障碍学会指南:双相障碍的管理显示文摘加拿大心境障碍与焦虑障碍治疗协作组(Canadian Network for Mood and Anxiety Treatments,CANMAT)曾于2005年发布了第1版双相障碍管理指南,并分别于2007、2009和2013年对该指南进行了更新,其中最近的2次更新是与国际双相障碍学会(International Society for Bipolar Disorders,ISBD)合作完成。2018版CANMAT/ISBD双相障碍治疗指南(以下简称指南)反映了自2005年首版指南发表以来本领域取得的重大进展,包括疾病诊断与疾病管理的更新以及药物治疗与心理治疗的近期研究进展。这些前沿进展中综合考虑了循证证据的级别,并基于治疗疗效、临床实践经验、安全性、耐受性和药物导致的转相风险等,对一线、二线及三线治疗方案进行了简明而清晰的推荐。本指南中新增内容涵盖了双相Ⅰ型障碍(BD-Ⅰ)的躁狂发作急性期、抑郁发作急性期和双相障碍维持期的一线及二线治疗推荐等级划分。这种对治疗推荐等级的划分综合考虑了治疗方法对双相障碍不同时相的影响,将进一步帮助临床医生做出基于循证证据的治疗决策。锂盐、喹硫平、双丙戊酸盐、阿塞那平、阿立哌唑、帕利哌酮、利培酮和卡利拉嗪单药或联合使用被推荐为躁狂发作急性期的一线治疗选择。BD-Ⅰ抑郁期的一线治疗选择包括喹硫平、鲁拉西酮、锂盐、拉莫三嗪单药,鲁拉西酮联合锂盐或双丙戊酸盐或拉莫三嗪辅助治疗。尽管急性期治疗有效的药物通常应继续用于BD-Ⅰ的维持期治疗,但也存在一些特殊情况(例如抗抑郁药)。现有数据表明,锂盐、喹硫平、双丙戊酸盐、拉莫三嗪、阿塞那平和阿立哌唑单药或联合治疗应被视为维持治疗的初始或更换治疗方案时的一线选择。除了探讨BD-Ⅰ的相关问题外,本指南中还对双相Ⅱ型障碍(BD-Ⅱ)的临床管理进行了系统回顾并给予治疗推荐,同时针对特殊人群也有相关推荐,如处于各个生殖周期的女性、儿童、青少年和老年人。此外,本指南中还讨论了特定精神疾病及共病(如物质滥用、焦虑障碍和代谢性疾病)的影响。最后,本指南中概述了安全性和药物监测的相关问题。CANMAT/ISBD工作组希望本指南能够成为全球临床医生的实用工具。 | Lakshmi N Yatham Sidney H Kennedy Sagar V Parikh Ayal Sehaffer David J Bond Benicio N Frey Verinder Sharma Benjamin I Goldstein Soham Rej Serge Beaulieu Martin Alda Glenda MaeQueen Roumen V Milev Arun Ravindran Claire O'Donovan Diane Mclntosh Raymond W Lam Gustavo Vazquez Flavio Kapczinski Roger S Melntyre Jan Kozicky Shigenobu Kanba Beny Lafer Trisha Suppes Joseph R Calabrese Eduard Vieta Gin Malhi Robert M Post Michael Berk 胡晨(译) 王刚(译) | 2019 | 中华精神科杂志2019，52，1： | 25 |
| 6 | On the combined effect of soil fertility and topography on tree growth in subtropical forest ecosystems—a study from SE China显示文摘Aims The aim of our research was to understand small-scale effects of topography and soil fertility on tree growth in a forest biodiversity and ecosystem functioning(BEF)experiment in subtropical SE China.Methods Geomorphometric terrain analyses were carried out at a spatial resolution of 5×5 m.Soil samples of different depth increments and data on tree height were collected from a total of 566 plots(667 m2 each).The soils were analyzed for carbon(soil organic carbon[SOC]),nitrogen,acidity,cation exchange capacity(CEC),exchangeable cations and base saturation as soil fertility attributes.All plots were classified into geomorphological units.Analyses of variance and linear regressions were applied to all terrain,soil fertility and tree growth attributes.Important Findings In general,young and shallow soils and relatively small differences in stable soil properties suggest that soil erosion has truncated the soils to a large extent over the whole area of the experiment.This explains the concurrently increasing CEC and SOC stocks downslope,in hollows and in valleys.However,colluvial,carbon-rich sediments are missing widely due to the convexity of the footslopes caused by uplift and removal of eroded sediments by adjacent waterways.The results showed that soil fertility is mainly influenced by topography.Monte-Carlo flow accumulation(MCCA),curvature,slope and aspect significantly affected soil fertility.Furthermore,soil fertility was affected by the different geomorphological positions on the experimental sites with ridge and spur positions showing lower exchangeable base cation contents,especially potassium(K),due to leaching.This geomorphological effect of soil fertility is most pronounced in the topsoil and decreases when considering the subsoil down to 50 cm depth.Few soil fertility attributes affect tree height after 1-2 years of growth,among which C stocks proved to be most important while pH_(KCl)and CEC only played minor roles.Nevertheless,soil acidity and a high proportion of Al on the exchange complex affected tree height even after only 1-2 years growth.Hence,our study showed that forest nutrition is coupled to a recycling of litter nutrients,and does not only depend on subsequent supply of nutrients from the mineral soil.Besides soil fertility,topography affected tree height.We found that especially MCCA as indicator of water availability affected tree growth at small-scale,as well as aspect.Overall,our synthesis on the interrelation between fertility,topography and tree growth in a subtropical forest ecosystem in SE China showed that topographic heterogeneity lead to ecological gradients across geomorphological positions.In this respect,small-scale soil-plant interactions in a young forest can serve as a driver for the future development of vegetation and biodiversity control on soil fertility.In addition,it shows that terrain attributes should be accounted for in ecological research. | Thomas Scholten Philipp Goebes Peter Kühn Steffen Seitz Thorsten Assmann Jürgen Bauhus Helge Bruelheide Francois Buscot Alexandra Erfmeier Markus Fischer Werner Härdtle Jin-Sheng He Keping Ma Pascal A.Niklaus Michael Scherer-Lorenzen Bernhard Schmid Xuezheng Shi Zhengshan Song Goddert von Oheimb Christian Wirth Tesfaye Wubet Karsten Schmidt | 2017 | Journal of Plant Ecology2017，10，1： | 22 |
| 7 | 细菌生物膜与抗生素耐药显示文摘抗生素耐药已成为一个全球关注的严重问题,也是科学界研究的热点问题.近年来的研究成果揭示,抗生素的耐药问题除了与耐药菌株的大量产生有关外,还与致病菌在人体内以生物膜(biofilms)的方式生长密切相关.生物膜是细菌粘附在物体表面上形成的一种具有高度结构性的膜状复合物,其主要成分为细菌分泌的胞外基质和细菌菌体.生物膜的形成显著增强了生物膜内细菌对抗生素、化学杀菌剂以及机体免疫系统的抵抗能力.结合国外近年来的研究成果,介绍了生物膜的发生发展,阐述了对人类健康的危害,重点讨论了细菌生物膜类感染难以根除的原因和对抗生素耐药的可能机制,并根据其特性对细菌生物膜类感染的防治提出一些看法. | 宋志军 吴红 Michael Givskov Niels Hφiby | 2003 | 自然科学进展2003，13，10： | 22 |
| 8 | Pancreatic regenerating protein (regⅠ) and regⅠreceptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis显示文摘AIM: Pancreatic regenerating protein (regⅠ) stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal andβ-cells. This suggests that regⅠand its receptor may play a role in recovery after pancreatic injury. We hypothesized that regⅠand its receptor are induced in acute pancreatitis. METHODS: Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls (4 rats/group). RegⅠreceptor mRNA, serum regⅠprotein, and tissue regⅠprotein levels were determined by Northern analysis, enzyme-linked immunosorbent assay (ELISA), and Western analysis, respectively. Immunohistochemistry was used to localize changes in regⅠand its receptor. RESULTS: Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum regⅠconcentrations from controls. However, Western blot demonstrated increased tissue levels of regⅠat 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in regⅠreceptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells. CONCLUSION: Acute pancreatitis results in increased tissue regⅠprotein levels localized to the acinar and ductal cells, and a parallel threefold induction of regⅠreceptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg I and its receptor may be important for recovery from acute pancreatitis. | Martin H Bluth Sameer A Patel Brian K Dieckgraefe Hiroshi Okamoto Michael E Zenilman | 2006 | World Journal of Gastroenterology2006，12，28： | 19 |
| 9 | 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 |
| 10 | 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 |
| 11 | Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma显示文摘瞄准:与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法:骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80, CD83, CD86 和 HLA 医生表示被分析。骨髓的的树枝状的房间从外部血被孤立,他们的功能被测试。吞噬作用用 FITC 葡聚糖祷告被分析,肽特殊刺激,在多形核白细胞 dI:dC 之上刺激 allogeneic T 房间和 cytokines 的分泌物的能力被测试。结果:骨髓的的树枝状的房间与 HCC 在病人被减少。在 CD80, CD83, CD86 和 HLA 医生表示的差别都没从 HCC 病人和健康控制在天真、刺激的骨髓的的树枝状的房间上被发现。肽 specific T 房间的正常吞噬作用或刺激与一个损害 allo-stimulatory 能力和减少的 IL-12 分泌物相对照被观察。结论:在病人的 mDCs 的损害 IL-12 生产能导致建议指导治疗可以提高的那 IL-12 的天真的 T 房间的一个损害 stimulatory 能力在 HCC 病人的肿瘤 specific 免疫者回答。 | Lars A Ormandy Anatol Frber Tobias Cantz Susanne Petrykowska Heiner Wedemeyer Monique Hrning Frank Lehner Michael P Manns Firouzeh Korangy Tim F Greten | 2006 | World Journal of Gastroenterology2006，12，20： | 12 |
| 12 | Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner显示文摘AIM:To investigate the role of osteopontin(OPN) and its splice variants in the proliferation of hepatocellular carcinoma(HCC).METHODS:The expression of OPN variants in HCC cell lines as well as HCC tissue samples and nontumour tissue was studied using polymerase chain reaction.OPN variant cDNAs were cloned into a mammalian expression vector allowing both transient expression and the production of stable OPN expressing cell lines.OPN expression was studied in these cells using Western blotting,immunofluoresnce and enzyme linked immunosorbent assay.A CD44 blocking antibody and siRNA targeting of CD44 were used to examine the role of this receptor in the OPN stimulated cell growth observed in culture.Huh-7 cells stably expressing either OPN-A,-B or-C were injected subcutaneously into the flanks of nude mice to observe in vivo tumour growth.Expression of OPN mRNA and protein in these tumours was examined using reverse transcriptionpolymerase chain reaction and immunohistochemistry.RESULTS:OPN is expressed in HCC in 3 forms,the full length OPN-A and 2 splice variants OPN-B and-C.OPN variant expression was noted in HCC tissue as well as cognate surrounding cirrhotic liver tissue.Expression of these OPN variants in the HCC derived cell line Huh-7 resulted in secretion of OPN into the culture medium.Transfer of OPN conditioned media to na ve Huh-7 and HepG2 cells resulted in significant cell growth suggesting that all OPN variants can modulate cell proliferation in a paracrine manner.Furthermore the OPN mediated increase in cellular proliferation was dependent on CD44 as only CD44 positive cell lines responded to OPN conditioned media while siRNA knockdown of CD44 blocked the proliferative effect.OPN expression also increased the proliferation of Huh-7 cells in a subcutaneous nude mouse tumour model,with Huh-7 cells expressing OPN-A showing the greatest proliferative effect.CONCLUSION:This study demonstrates that OPN plays a significant role in the proliferation of HCC through interaction with the cell surface receptor CD44.Modulation of this interaction could represent a novel strategy for the control of HCC. | Renee J Phillips Karla J Helbig Kylie H Van der Hoek Devanshi Seth Michael R Beard | 2012 | World Journal of Gastroenterology2012，18，26： | 12 |
| 13 | Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells显示文摘Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate(CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review:nanostructured calcium phosphate cement(CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen:(i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements;(ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals;(iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials;(iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and(v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments. | Ping Wang Liang Zhao Jason Liu Michael D Weir Xuedong Zhou Hockin H K Xu | 2014 | Bone Research2014，2，3： | 11 |
| 14 | 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 |
| 15 | Tyrosine kinase of insulin-like growth factor receptor as target for novel treatment and prevention strategies of colorectal cancer显示文摘AIM: To investigate the antineoplastic potency of the novel insulin-like growth factor 1 receptor (IGF-1R) tyro- sine kinase inhibitor (TKI) NVP-AEW541 in cell lines and primary cell cultures of human colorectal cancer (CRC). METHODS: Cells of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal violet stain- ing were used for analysis of growth factor receptor pro- tein expression and detection of cell number changes, respectively. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydro- genase (LDH). The proportion of apoptotic cells was determined by quantifying the percentage of sub-G1 (hypodiploid) cells. Cell cycle status reflected by the DNA content of the nuclei was detected by flow cytometry. RESULTS: NVP-AEW541 dose-dependently inhibited the proliferation of colorectal carcinoma cell lines and primary cell cultures by inducing apoptosis and cell cycle arrest. Apoptosis was characterized by caspase-3 activa- tion and nuclear degradation. Cell cycle was arrested at the G1/S checkpoint. The NVP-AEW541-mediated cell cycle-related signaling involved the inactivation of Akt and extracellular signal-regulated kinase (ERK) 1/2, the upregulation of the cyclin-dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. Moreover, BAX was upregu- lated during NVP-AEW541-induced apoptosis, whereas Bcl-2 was downregulated. Measurement of LDH release showed that the antineoplastic effect of NVP-AEW541 was not due to general cytotoxicity of the compound. However, augmented antineoplastic effects were ob-served in combination treatments of NVP-AEW541 with either 5-FU, or the EGFR-antibody cetuximab, or the HMG-CoA-reductase inhibitor fluvastatin. CONCLUSION: IGF-1R-TK inhibition is a promising novel approach for either mono- or combination treatment strategies of colorectal carcinoma and even for CRC che- moprevention. | Michael Hpfner Andreas P Sutter Alexander Huether Viola Baradari Hans Scherübl | 2006 | World Journal of Gastroenterology2006，12，35： | 10 |
| 16 | Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells显示文摘AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin) or the novel anticancer agents sorafenib or bortezomib. METHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry.RESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275-induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G1/S checkpoint, which was associated with induction of the cyclin-dependent kinase inhibitor p21Waf/CIP1. Furthermore, additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multi-kinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects.CONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new, targeted anticancer agents. | Viola Baradari Michael Hpfner Alexander Huether Detlef Schuppan Hans Scherübl | 2007 | World Journal of Gastroenterology2007，13，33： | 10 |
| 17 | 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 |
| 18 | Implications of preoperative hypoalbuminemia in colorectal surgery显示文摘Serum albumin has traditionally been used as a quantitative measure of a patient's nutritional status because of its availability and low cost. While malnutrition has a clear definition within both the American and European Societies for Parenteral and Enteral Nutrition clinical guidelines, individual surgeons often determine nutritional status anecdotally. Preoperative albumin level has been shown to be the best predictor of mortality after colorectal cancer surgery. Specifically in colorectal surgical patients, hypoalbuminemia significantly increases the length of hospital stay, rates of surgical site infections, enterocutaneous fistula risk, and deep vein thrombosis formation. The delay of surgical procedures to allow for preoperative correction of albumin levels in hypoalbuminemic patients has been shown to improve the morbidity and mortality in patients with severe nutritional risk. The importance of preoperative albumin levels and the patient's chronic inflammatory state on the postoperative morbidity and mortality has led to the development of a variety of surgical scoring systems to predict outcomes efficiently. This review attempts to provide a systematic overview of albumin and its role and implications in colorectal surgery. | Adam Truong Mark H Hanna Zhobin Moghadamyeghaneh Michael J Stamos | 2016 | World Journal of Gastrointestinal Surgery2016，8，5： | 9 |
| 19 | Risk factors for colonoscopic perforation: A population-based study of 80118 cases显示文摘AIM: To assess the incidence and risk factors associated with colonic perforation due to colonoscopy. METHODS: This was a retrospective cross-sectional study. Patients were retrospectively eligible for inclusion if they were 18 years and older and had an inpatient or outpatient colonoscopy procedure code in any facility within the Geisinger Health System during the period from January 1, 2002 to August 25, 2010. Data are presented as median and inter-quartile range, for continuous variables, and as frequency and percentage for categorical variables. Baseline comparisons across those with and without a perforation were made using the two-sample t -test and Pearson's χ2 test, as appropriate.RESULTS: A total of 50 perforations were diagnosed out of 80118 colonoscopies, which corresponded to an incidence of 0.06% (95%CI: 0.05-0.08) or a rate of 6.2 per 10000 colonoscopies. All possible risk factors associated with colonic perforation with a P -value < 0.1 were checked for inclusion in a multivariable logbinomial regression model predicting 7-d colonic perforation. The final model resulted in the following risk factors which were significantly associated with risk of colonic perforation: age, gender, body mass index, albumin level, intensive care unit (ICU) patients, inpatient setting, and abdominal pain and Crohn's disease as indications for colonoscopy. CONCLUSION: The cumulative 7 d incidence of colonic perforation in this cohort was 0.06%. Advanced age and female gender were significantly more likely to have perforation. Increasing albumin and BMI resulted in decreased risk of colonic perforation. Having a colonoscopy indication of abdominal pain or Crohn's disease resulted in a higher risk of colonic perforation. Colonoscopies performed in inpatients and particularly the ICU setting had substantially greater odds of perforation. Biopsy and polypectomy did not increase the risk of perforation and only three perforations occurred with screening colonoscopy. | Uzair Hamdani Raza Naeem Fyeza Haider Pardeep Bansal Michael Komar David L Diehl H Lester Kirchner | 2013 | World Journal of Gastroenterology2013，19，23： | 9 |
| 20 | STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation显示文摘 | Wanqiang Sheng Fan Yang Yi Zhou Henry Yang Pey Yng Low David Michael Kemeny Patrick Tan Akira Moh Mark H Kaplan Yongliang Zhang Xin-Yuan Fu | 2014 | Cell Research2014，24，12： | 7 |
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