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1自发性脑出血管理指南 美国心脏协会/美国卒中协会针对医疗专业人员的指南显示文摘目的本指南旨在为自发性脑出血的诊断和治疗提供最新的全面推荐意见。方法利用PubMed进行规范化文献检索,检索时间至2013年8月底。撰写委员会成员通过远程电信会议讨论指南内容及推荐意见,采用美国心脏协会/美国卒中协会的疗效确定性水平和证据分级方案对推荐意见进行分级。由6位同行评议专家以及卒中委员会科学声明监督委员会和卒中委员会领导委员会成员对指南草案进行发表前审阅。结果本文为急性脑出血患者的医疗诊治提供了循证指南,重点包括诊断、凝血功能障碍和血压管理、继发性脑损伤防治、颅内压控制、外科治疗的作用、转归预测、康复、二级预防以及将来需要考虑的问题。本指南已纳入最新的3期临床试验结果。结论脑出血是一种需要进行早期积极救治的危重疾病。本指南为脑出血患者的目标导向治疗提供了一个框架。J. Claude Hemphill Ⅲ Steven M. Greenberg Craig S. Anderson Kyra Beckelr Bernard R. Bendok Mary Cushman Gordon L. Fung Joshua N. Goldstein R. LochMacdonald Pamela H Mitchell, Phillip A Scott,Magdy H Selim, Daniel Woo 高圆圆 徐欣 2015国际脑血管病杂志2015,23,10:444
2Non-alcoholic fatty liver disease and the metabolic syndrome:An update显示文摘Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic in westernized countries, subsequently increasing the risk for developing the metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). NAFLD is estimated to affect approximate 30% of the general US population and is considered the hepatic manifestation of the metabolic syndrome. Recent findings linking the components of the metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis (NASH) will be reviewed; in particular, the role of visceral adipose tissue, insulin resistance, and adipocytokines in the exacerbation of these conditions. While no therapy has been proven effective for treating NAFLD/NASH, common recommendations will be discussed.R Scott Rector John P Thyfault Yongzhong Wei Jamal A Ibdah 2008World Journal of Gastroenterology2008,14,2:60
3Nonalcoholic fatty liver disease and mitochondrial dysfunction显示文摘Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as 'cellular power plants'. Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.Yongzhong Wei R Scott Rector John P Thyfault Jamal A Ibdah 2008World Journal of Gastroenterology2008,14,2:32
4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
5Endoscopy and polyps-diagnostic and therapeutic advances in management显示文摘Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options.Scott R Steele Eric K Johnson Bradley Champagne Brad Davis Sang Lee David Rivadeneira Howard Ross Dana A Hayden Justin A Maykel 2013World Journal of Gastroenterology2013,19,27:16
6The 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 2019Genes & Diseases2019,6,3:15
7Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine显示文摘AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination.Scott Bowden Stephen Locarnini Ting-Tsung Chang You-Chen Chao Kwang-Hyub Han Robert G Gish Robert A de Man Miao Yu Cyril Llamoso Hong Tang 2015World Journal of Gastroenterology2015,21,15:11
8Management of gastroesophageal reflux disease: Patient and physician communication challenges and shared decision making显示文摘Gastroesophageal reflux disease(GERD) is a common upper esophageal condition and typical symptoms can include heartburn and sensation of regurgitation while atypical symptoms include chronic cough, asthma, hoarseness, dyspepsia and nausea. Typically, diag-nosis is presumptive given the presence of typical and atypical symptoms and is an indication for empiric therapy. Treatment management can include lifestyle modifications and/or medication therapy with proton pump inhibitor(PPI) class being the preferred and most effective. Complete symptom resolution is not always achieved and long-term PPI therapy can put patients at risk for serious side effects and needless expense. The brain-gut connection and hypervigilance plays an important role in symptom resolution and treatment success, especially in the case of non-PPI responders. Hypervigilance is a combination of increased esophageal sensory sensitivity in combination with exaggerated threat perception surrounding esophageal symptoms. Hypervigilance requires a different approach to GERD managements, where continued PPI therapy and surgery are usually not recommended. Rather, helping physicians and patients understand the brain-gut connection can guide and improve care.Education and reassurance should be the main pillars or treatment. However, it is important not to suggest the symptoms are due to anxiety alone, this often leads to patient dissatisfaction. Patient dissatisfaction with treatment reveals the need for a more patient-centered approach to GERD management and better communication between patients and providers. Shared decision making(SDM) with the incorporation of patient-reported outcomes(PRO) promotes patient adherence and satisfaction. SDM is a joint discussion between clinician and patient in which a mutually shared solution is explored for GERD symptoms. For SDM to work the physician needs to capture patients' perceptions which may not be obtained in the standard interview. This can be done through the use of PROs which promote a dialogue with patients about their symptoms and treatment priorities in the context of the SDM patient encounter. SDM could potentially help in the management of patient expectations for GERD treatment, ultimately positively impacting their health-related quality of life.Scott Klenzak Igor Danelisen Grace D Brannan Melissa A Holland Miranda AL van Tilburg 2018World Journal of Clinical Cases2018,6,15:10
9Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases显示文摘Discoveries in the first few years of the 21st century have led to an understanding of important interactions between the nervous system and the inflammatory response at the molecular level, most notably the acetylcholine (ACh)- triggered, a7-nicotinic acetylcholine receptor (a7nAChR)- dependent nicotinic anti-inflammatory pathway. Studies using the a7nAChR agonist, nicotine, for the treatment of mucosal inflammation have been undertaken but the efficacy of nicotine as a treatment for inflammatory bowel diseases remains debatable. Further understanding of the nicotinic anti-inflammatory pathway and other endogenous anti-inflammatory mechanisms is required in order to develop refined and specific therapeutic strategies for the treatment of a number of inflammatory diseases and conditions, including periodontitis, psoriasis, sarcoidosis, and ulcerative colitis.David A Scott Michael Martin 2006World Journal of Gastroenterology2006,12,46:8
10Sphingosine-1-phosphate signaling in vasculogenesis and angiogenesis显示文摘Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive network of signaling cascades downstream from at least three of the nine known G-protein-coupled sphingosine-1-phosphate (S1P) receptors act as a prime effector of neovascularization that occurs in embryonic development and in association with various pathologies. This review focuses on the current knowledge of the roles of S1P signaling in vasculogenesis and angiogenesis, with particular emphasis on vascular cell adhesion and motility responses.Kelley M Argraves Brent A Wilkerson W Scott Argraves 2010World Journal of Biological Chemistry2010,1,10:6
11两件西汉时期鎏金与鎏银青铜器镀层中的金属化合物显示文摘采用金相显微分析、环境扫描电子显微镜、X射线衍射、X射线荧光对两件西汉时期的鎏金与鎏银青铜马镳进行了分析 ,揭示了西汉时期鎏金与鎏银青铜器的部分金相学特征和部分金属化合物 ,研究结果表明我国西汉时期已采用了金汞齐与银汞齐在铅锡铜合金表面火法鎏金和鎏银技术。马清林 Scott David A 2004文物保护与考古科学2004,16,2:6
12Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells显示文摘Saiyong Zhu Raiesh Ambasudhan Woong Sun Hyun Jung Kim Maria Talantova Xiaojing Wang Mingliang Zhang Yu Zhang Timothy Laurent James Parker Han-Seop Kim Jeffrey D Zaremba Sofiyan Saleem Sara Sanz-Blasco Eliezer Masliah Scott R McKercher Yee Sook Cho Stuart A Lipton Janghwan Kim Sheng Ding 2014Cell Research2014,24,1:6
13Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases.Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy 2015World Journal of Gastrointestinal Pharmacology and Therapeutics2015,6,4:5
14General review of magnetic resonance elastography显示文摘Magnetic resonance elastography(MRE) is an innovative imaging technique for the non-invasive quantification of the biomechanical properties of soft tissues via the direct visualization of propagating shear waves in vivo using a modified phase-contrast magnetic resonance imaging(MRI) sequence. Fundamentally,MRE employs the same physical property that physicians utilize when performing manual palpation- that healthy and diseased tissues can be differentiated on the basis of widely differing mechanical stiffness. By performing 'virtual palpation ',MRE is able to provide information that is beyond the capabilities of conventional morphologic imaging modalities. In an era of increasing adoption of multi-parametric imaging approaches for solving complex problems,MRE can be seamlessly incorporated into a standard MRI examination to provide a rapid,reliable and comprehensive imaging evaluation at a single patient appointment. Originally described by the Mayo Clinic in 1995,the technique represents the most accurate non-invasive method for the detection and staging of liver fibrosis and is currently performed in more than 100 centers worldwide. In this general review,the mechanical properties of soft tissues,principles of MRE,clinical applications of MRE in the liver and beyond,and limitations and future directions of this discipline-are discussed. Selected diagrams and images are provided for illustration.Gavin Low Scott A Kruse David J Lomas 2016World Journal of Radiology2016,8,1:5
15The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases显示文摘在他们描述脱氧核糖核酸双螺旋,沃森和克里克的结构写了什么可以是在科学文学的最大的保守的陈述之一的精液的出版,也就是那“这没疏忽特定的配对我们立即要求了为遗传物质建议可能的拷贝机制。“半个世纪以后,我们更充分欣赏它是与精确性复制 60 亿核苷酸的巨大的挑战需要稳定地在许多代上维持人的染色体的。这挑战也许比大 50 年以前被认识到,因为随后的研究表明了染色体能被在脱氧核糖核酸而且由现在质问到复制的正常脱氧核糖核酸的各种各样的顺序主题产生潜在地细胞毒素、诱变的损害的一个大数字和变化的环境压力使动摇不仅。向染色体稳定性的许多决定因素的更好的理解,这章考察 undamaged 和损坏脱氧核糖核酸与被拷贝的忠实,与真核细胞的 B 家庭和 Y 家庭 DNA 的一个焦点,并且考虑这忠实怎么被完成。Scott D McCulloch Thomas A Kunkel 2008Cell Research2008,18,1:5
16Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer显示文摘Douglas K Rex John H Bond Sidney Winawer Theodore R Levin Randall W Burt David A Johnson Lynne M Kirk Scott Litlin David A Lieberman Jerome D Waye James Church John B Marshall Robert H Riddell 2002The American Journal of Gastroenterology2002,,6:3
17Sacroiliac joint stability: Finite element analysis of implant number, orientation, and superior implant length显示文摘AIM To analyze how various implants placement variables affect sacroiliac(SI) joint range of motion. METHODS An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the SI joint using various placement configurations of triangular implants(iF use Implant System~?). Placement configurations were varied by changing implant orientation, superior implant length, and number of implants. The range of motion of the SI joint was calculated using a constant moment of 10 N-m with a follower load of 400 N. The changes in motion were compared between the treatment groups to assess how the different variables affected the overall motion of the SI joint. RESULTS Transarticular placement of 3 implants with superior implants that end in the middle of the sacrum resulted in the greatest reduction in range of motion(flexion/extension = 73%, lateral bending = 42%, axial rotation = 72%). The range of motions of the SI joints were reduced with use of transarticular orientation(9%-18%) when compared with an inline orientation. The use of a superior implant that ended mid-sacrum resulted in median reductions of(8%-14%) when compared with a superior implant that ended in the middle of the ala. Reducing the number of implants, resulted in increased SI joint range of motions for the 1 and 2 implant models of 29%-133% and 2%-39%, respectively,when compared with the 3 implant model.CONCLUSION Using a validated finite element model we demonstrated that placement of 3 implants across the SI joint using a transarticular orientation with superior implant reaching the sacral midline resulted in the most stable construct. Additional clinical studies may be required to confirm these results.Derek P Lindsey Ali Kiapour Scott A Yerby Vijay K Goel 2018World Journal of Orthopedics2018,9,3:3
18Cadmium, Environmental Exposure, and Health Outcomes显示文摘Satarug Soisungwan Garrett Scott H Sens Mary Ann Sens Donald A 2010Environmental Health Perspectives2010,,2:3
19宋代铁钱的中子衍射研究显示文摘利用飞行时间法中子衍射技术(time of flight neutron diffraction)对3枚陕西出土的宋代铁钱进行了无损的相分析,采用英国卢瑟福实验室的高分辨率中子衍射仪GEM(General Materials Diffractometer),定量地揭示了铁钱的相组成、合金成分与主要锈蚀产物的成分。分析结果表明铁钱的主要物相为铁素体、渗碳体(还含有Fe3P),主要锈蚀产物为棕黄色针铁矿(α-FeOOH),没有发现铁素体晶粒的织构化,表明铁钱系铸造而成。中子衍射这种完全无损且量化的物理实验技术在中国文化遗产的科学分析与保护研究中具有广阔的应用前景。黄维 Winfried Kockelmann Evelyn Gordfrey David A Scott 吴小红 2010北京大学学报(自然科学版)2010,46,2:3
20Guanylyl cyclase C signaling axis and colon cancer prevention显示文摘Colorectal cancer(CRC) is a major cause of cancerrelated mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C(GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms. These effects are mediated by the endogenous hormones guanylin(GUCA2A) and uroguanylin(GUCA2B), which bind and activate GUCY2 C to regulate proliferation, metabolism and barrier function in intestine. Recent studies have demonstrated a link between GUCY2 C silencing and intestinal dysfunction, including tumorigenesis. Indeed, GUCY2 C silencing by the near universal loss of its paracrine hormone ligands increases colon cancer susceptibility in animals and humans. GUCY2C's role as a tumor suppressor has opened the door to a new paradigm for CRC prevention by hormone replacement therapy using synthetic hormone analogs, such as the FDA-approved oral GUCY2 C ligand linaclotide(Linzess^(TM)). Here we review the known contributions of the GUCY2 C signaling axis to CRC, and relate them to a novel clinical strategy targeting tumor chemoprevention.Amanda M Pattison Dante J Merlino Erik S Blomain Scott A Waldman 2016World Journal of Gastroenterology2016,22,36:2
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