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| 1 | Cirrhotic portal hypertension: From pathophysiology to novel therapeutics显示文摘Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis. | Lakmie S Gunarathne Harinda Rajapaksha Nicholas Shackel Peter W Angus Chandana B Herath | 2020 | World Journal of Gastroenterology2020，26，40： | 24 |
| 2 | 亚太地区胃食管反流病的处理共识:更新版显示文摘背景与目的:自从2004年亚太地区胃食管反流病(GERD)共识发表以来,更多关于GERD流行病学和处理的文献资料相继出现。有必要对这些资料进行循证综述,对共识作出更新。方法:由多学科专家组应用德尔菲(Delphi)法制定共识条文,提呈相关资料,并对证据质量、推荐力度和共识水平进行分级。结果:亚洲GERD发生率日益增加。其危险因素包括老年、男性、种族、家族史、社会经济地位高、体重指数增加和吸烟。对于有典型症状而无报警症状的患者,对质子泵抑制剂(PPI)试验有症状应答具有诊断意义。如PPI试验失败,停止治疗后pH监测结果阴性可排除GERD。窄带成像、胶囊内镜检查和无线pH监测的作用尚未明确。亚洲诊断策略的制定须考虑到并存的胃癌和消化性溃疡。减轻体质量和抬高床头可改善反流症状。PPIs是最有效的内科治疗手段。对于非糜烂性反流病(NERD)患者,按需治疗较为适宜。有慢性咳嗽、喉炎和典型GERD症状的患者在排除非GERD病因后,应予PPI每天两次治疗。如有经验丰富的外科医师,GERD患者可行胃底折叠术。除临床试验外,GERD不应采用内镜治疗。结论:新的诊断方法和内镜治疗的作用有待进一步研究阐明。亚洲GERD诊断策略的制定须考虑到并存的胃癌和消化性溃疡。PPIs仍为治疗的基石。 | Kwong Ming Fock Nicholas J Talley Ronnie Fass Khean Lee Goh Peter Katelaris Richard Hunt Michio Hongo Tiing Leong Ang Gerald Holtmann Sanjay Nandurkar San Ren Lin Benjamin CY Wong Francis KL Chan Abdul Aziz Rani Young-Tae Bak Jose Sollano Khek Yu Ho Sathoporn Manatsathit 钱本余 | 2008 | 胃肠病学2008，13，7： | 21 |
| 3 | Homocysteine alters monocyte-endothelial interaction in vitro显示文摘Objective To determine whether homocysteine induced endothelial damage through monocyte-endothelial interaction and to characterize both cell types in vitro. Methods Radiomethods were performed on monocyte adhesion to/through endothelium and endothelial damage experiments. Results Homocysteine-treated endothelial cells increased monocyte adhesion and transmigration. Homocysteine-treated monocytes induced endothelial detachment, but this effect was blocked by catalase. These effects were increased with higher concentrations of homocysteine. Monocyte surface glycoprotein antibodies CD11b/CD18 and CD14 inhibited these processes.Conclusions Homocysteine alters monocyte-endothelial interaction in vitro, eventually bringing about endothelial damage through release of H 2O 2. These phenomena are mediated through monocyte surface glycoproteins CD11b/CD18 and CD14. Upregulation of these processes in vivo may contribute to acceleration of atherosclerosis in patients with elevated plasma homocysteine levels. | 郭雪微 Dudman Nicholas Peter | 2003 | Chinese Medical Journal2003，，1： | 17 |
| 4 | Characterization of Gibberellin Receptor Mutants of Barley (Hordeum vulgare L.)显示文摘Gid1 的顺序(为赤霉素(GA ) 的基因从米饭的受体) 被用来从大麦识别通常认为的 orthologue。这在 E 被表示。coli,并且生产了能与结构的特性和 saturability 在 vitro 绑 GA 的蛋白质。它在 GA 回答的潜在的角色与减少的 GA 敏感(gse1 异种) 用大麦异种被调查。十六不同 gse1 异种各在这个序列带了唯一的核苷酸替换。在里面几乎一个案例,这些变化导致了单个氨基酸替换,并且,为留下的异种,在 mRNA 的 5 untranslated 区域的替换被建议防碍翻译开始。在分离有完美的连接在新变异的等位基因和 gse1 显型之间的人口,导致在大麦的通常认为的 GID1 GA 受体顺序对应于 Gse1 地点的结论。在异种之一的内长的 GA 内容的决心揭示了 C20 GA 先锋的 bioactive GA1,和赤字的提高的累积。所有在通常正在浸透的集中 gse1 异种把敏感归结为外长的 GA3,并且到 AC94377 (GA 类似物) ,,但是,在高得多的集中,经常有可观的回答。在大麦和米饭异种之间的比较揭示这之间的有趣的差别在 GA 的二谷物种神经质的生理学。 | Peter M. Chandler Carol A. Harding Anthony R. Ashton Mark D. Mulcair Nicholas E. Dixonb Lewis N. Manderb | 2008 | Molecular Plant2008，1，2： | 10 |
| 5 | User-Level Device Drivers: Achieved Performance显示文摘Running device drivers as unprivileged user-level code, encapsulated into their own process, has often been proposed as a technique for increasing system robustness. However, in the past, systems based on user-level drivers have generally exhibited poor I/O performance. Consequently, user-level device drivers have never caught on to any significant degree. In this paper we demonstrate that it is possible to build systems which employ user-level device drivers, without significant performance degradation, even for high-bandwidth devices such as Gigabit Ethernet. | Ben Leslie Peter Chubb Nicholas Fitzroy-Dale Stefan Gotz Charles Gray Luke Macpherson Daniel Potts Yue-Ting Shen Kevin Elphinstone Gernot Heiser | 2005 | Journal of Computer Science & Technology2005，20，5： | 7 |
| 6 | A history of high-power laser research and development in the United Kingdom显示文摘The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years. | Colin N.Danson Malcolm White John R.M.Barr Thomas Bett Peter Blyth David Bowley Ceri Brenner Robert J.Collins Neal Croxford A.E.Bucker Dangor Laurence Devereux Peter E.Dyer Anthony Dymoke-Bradshaw Christopher B.Edwards Paul Ewart Allister I.Ferguson John M.Girkin Denis R.Hall David C.Hanna Wayne Harris David I.Hillier Christopher J.Hooker Simon M.Hooker Nicholas Hopps Janet Hull David Hunt Dino A.Jaroszynski Mark Kempenaars Helmut Kessler Sir Peter L.Knight Steve Knight Adrian Knowles Ciaran L.S.Lewis Ken S.Lipton Abby Littlechild John Littlechild Peter Maggs Graeme P.A.Malcolm OBE Stuart P.D.Mangles William Martin Paul McKenna Richard O.Moore Clive Morrison Zulfikar Najmudin David Neely Geoff H.C.New Michael J.Norman Ted Paine Anthony W.Parker Rory R.Penman Geoff J.Pert Chris Pietraszewski Andrew Randewich Nadeem H.Rizvi Nigel Seddon MBE Zheng-Ming Sheng David Slater Roland A.Smith Christopher Spindloe Roy Taylor Gary Thomas John W.G.Tisch Justin S.Wark Colin Webb S.Mark Wiggins Dave Willford Trevor Winstone | 2021 | High Power Laser Science and Engineering2021，9，2： | 5 |
| 7 | Ionotropic receptors and ion channels in ischemic neuronal death and dysfunction显示文摘到神经原的精力供应的损失在击期间导致被称为缺氧的去极的膜潜力的快速的损失。因为离子的流动的 dysregulation 和 ATP 的损失,缺氧的去极在神经原上导致巨大的生理的应力驾驶维持电气化学的坡度的离子泵。在这评论,我们在场一些被认为贡献神经原并且随后的缺氧的去极的 ionotropic 受体和离子隧道的概述,到房间死亡。为作为门 ligand 的阳离子隧道工作的 glutamate 和 ATP 的 ionotropic 受体在神经原的死亡和机能障碍是批评的。有趣地,二这些受体(P2X7 和 NMDAR ) 被显示了联合离子隧道到 pannexin-1 (Panx1 ) 。我们也讨论短暂受体潜力(TRP ) 的重要角色响应局部缺血的隧道和酸察觉到的离子隧道(ASIC ) 。从我们缺氧的去极的当前的理解出现的中央挑战是需要阐明这些离子隧道到的机械学、时间的相互关系充分在击期间在神经原上欣赏他们的影响。 | Nicholas L WEILINGER Valentyna MASLIEIEVA Jennifer BIALECKI Sarup S SRIDHARAN Peter L TANG Roger J THOMPSON | 2013 | Acta Pharmacologica Sinica2013，34，1： | 5 |
| 8 | Perturbation of Wood Cellulose Synthesis Causes Pleiotropic Effects in Transgenic Aspen显示文摘在树上的纤维素生合成的基因操作可以提供新奇卓见进树的生长和发展。探索这可能性,一棵白杨的 overexpression 第二等的联系墙的纤维素 synthase (PtdCesA8 ) 基因在转基因的白杨(Populus tremuloides L.) 被尝试并且出人意料地象它的内长的对应物一样导致了 transgene 的 silencing。转基因的白杨植物的主要的轴快速停止成长,并且弱树枝采用了一个哭泣的生长习惯。而且,转基因的植物开始开发了更小的叶子和一个不太广泛的根系统。几乎没象 10% 纤维素一样包含的转基因的白杨植物的第二等的木部(木头) 使正常化与典型地在正常白杨木头发现的 41% 纤维素相比弄干重量。在纤维素的这巨大的减小被木质素(35%) 和非有纤维质的多糖(55%) 的比例的增加在控制植物与 22% 木质素和 36% 非有纤维质的多糖相比伴随。生产的转基因的茎典型崩溃或改变了第二等的墙形态学并且极大地包含了的不规则的木部容器减少了水晶的纤维素的数量。这些结果在维持要求在树上建立垂直生长习惯的力量和结构的正直在第二等的木部以内表明第二等的墙纤维素的基本角色。 | Chandrashekhar R Joshi Shivegowda Thammannagowda Takeshi Fujino Ji-Qing Gou Utku Avci Candace H. Haigler Lisa M. McDonnell Shawn D. Mansfield Bemnet Mengesha Nicholas C. Carpita Darby Harris Seth DeBolt Gary F. Peter | 2011 | Molecular Plant2011，4，2： | 4 |
| 9 | U. S. Householder survey of functional gastrointestinal disorders显示文摘 | Douglas A. Drossman Zhiming Li Eileen Andruzzi Robert D. Temple Nicholas J. Talley W. Grant Thompson William E. Whitehead Josef Janssens Peter Funch-Jensen Enrico Corazziari Joel E. Richter Gary G. Koch | 1993 | Digestive Diseases and Sciences1993，，9： | 4 |
| 10 | 1H nuclear magnetic resonance spectroscopy-basedmetabonomic study in patients with cirrhosis and hepaticencephalopathy显示文摘AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics.METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H- nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients(FID's) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups.RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate(0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate(0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine(0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine(0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine(0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate(1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate(1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01), pyruvate(0.11 ± 0.02 vs 0.03 ± 0.00, P < 0.01) threonine(0.39 ± 0.02 vs 0.08 ± 0.01, P < 0.01) and aspartate(0.37 ± 0.03 vs 0.03 ± 0.01). A five metabolite signature by stepwise discriminant analysis could separate between controls and cirrhotic patients with an accuracy of 98%. In patients with encephalopathy we observed further derangement of ketone body metabolism, impaired production of glycerol and myoinositol, reversal of Fischer's ratio and impaired glutamine production as demonstrated by lower b-hydroxybutyrate(0.58 ± 0.14 vs 0.16 ± 0.02, P < 0.0002), higher acetoacetate(0.23 ± 0.02 vs 0.41 ± 0.16, P < 0.05), leucine(0.33 ± 0.02 vs 0.49 ± 0.05, P < 0.005) and isoleucine(0.12 ± 0.02 vs 0.27 ± 0.02, P < 0.0004) and lower glutamine(0.44 ± 0.08 vs 0.36 ± 0.04, P < 0.013), glycerol(0.53 ± 0.03 vs 0.19 ± 0.02, P < 0.000) and myoinositol(0.36 ± 0.04 vs 0.18 ± 0.02, P < 0.010) concentrations. A four metabolite signature by stepwise discriminant analysis could separate between encephalopathic and cirrhotic patients with an accuracy of 87%.CONCLUSION: Patients with cirrhosis and patients with hepatic encephalopathy exhibit distinct metabolic abnormalities and the use of metabonomics can select biomarkers for these diseases. | Konstantinos John Dabos John Andrew Parkinson Ian Howard Sadler John Nicholas Plevris Peter Clive Hayes | 2015 | World Journal of Hepatology2015，7，12： | 3 |
| 11 | A software-defined networking approach for handover management with real-time video in WLANs显示文摘To achieve high performance and reliability in video streaming over wireless local area networks (WLANs), one must jointly consider both optimized association to access points (APs) and handover management based on dynamic scanning of alternate APs. In this article, we propose a new architecture within the software-defined networking (SDN) framework, which allows stations to be connected to several APs simultaneously and to switch fast between them. We evaluate our system in a real-time testbed and demonstrate that our SDN-based handover mechanism significantly reduces the number and duration of video freeze events and allows for smaller playout buffers. | Peter Dely Andreas Kassler Lawrence Chow Nicholas Bambos Nico Bayer Hans Einsiedler Christoph Peylo Daniel Mellado Miguel Sanchez | 2013 | Journal of Modern Transportation2013，21，1： | 3 |
| 12 | Characterization of colonic dendritic cells in normal and colitic mice显示文摘AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC.METHODS: Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2-/-) mice that develop colitis.RESULTS: In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c+, CD11b+,B220-, CD8α-) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40,and had high endocytic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN).The majority (>85%) of DC in the colon and MLN of IL2-/-mice were type 1 myeloid, and expressed high levels of MHC class Ⅱ, CD80, CD86, CD 40, DEC 205, and CCR5molecules and were of low endocytic activity consistent with mature DC.CONCLUSION: These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon. | Sheena M Cruickshank Nicholas R English Peter J Felsburg Simon R Carding | 2005 | World Journal of Gastroenterology2005，11，40： | 3 |
| 13 | 抗生素耐药性环境中产生和转移的人类健康风险评估(HHRA)显示文摘[背景]直到最近,人们才明确环境能影响抗生素耐药性风险对临床结果的影响,但迄今为止,很少有文献记录正式评估这些风险的方法。[目标]我们研究可能的方法,并试图确定人类健康风险评估(HHRA)的研究需求,这项评估注重环境在抗生素耐药性病原体所致的抗生素治疗失败中所起的作用。[方法]作者参加了2012年3月4—8日在加拿大魁北克省举行的研讨会,定义抗生素耐药性风险与人类健康环境评估的范围和目标。我们专注于环境中耐药性产生'热点区域'的关键要素,(与食品无关的)暴露评估以及剂量反应,以描述风险特征,从而改善抗生素耐药性管理的方案。[讨论]识别传统风险评估中有助于评估环境中抗生素耐药性的各个新方面。包括:a)解释附加的选择压力对环境耐药基因组的作用,即随着时间的推移,促使抗生素耐药性细菌(ARB)产生;b)在相关的环境组成部分的'热点区域'中识别和描述水平基因转移(HGT)率;c)针对不同健康结局和途径的ARB剂量修改传统的剂量反应方法。[结论]我们建议将抗生素耐药性产生造成的环境影响纳入所有涉及ARB的HHRA过程之中。由于可用的数据有限,一种多标准决策分析方法将有助于进行环境中抗生素耐药性的HHRA,并使风险管理者了解环境抗生素耐药性。 | Nicholas J.Ashbolt Alejandro Amézquita Thomas Backhaus Peter Borriello Kristian K.Brandt Peter Collignon Anja Coors Rita Finley William H.Gaze Thomas Heberer John R.Lawrence D.G.Joakim Larsson Scott A.McEwen James J.Ryan Jens Schnfeld Peter Silley Jason R.Snape Christel Van den Eede Edward Topp 王晓宇 张伊人 操仪 | 2014 | 环境与职业医学2014，31，2： | 3 |
| 14 | Short-Term Outcomes of the Australasian Randomized Clinical Study Comparing Laparoscopic and Conventional Open Surgical Treatments for Colon Cancer: The ALCCaS Trial显示文摘 | Peter J. Hewett Randall A. Allardyce Philip F. Bagshaw Christopher M. Frampton Francis A. Frizelle Nicholas A. Rieger J Shona Smith Michael J. Solomon Jacqueline H. Stephens Andrew R. L. Stevenson | 2008 | Annals of Surgery2008，，5： | 3 |
| 15 | Bayesian analysis of stochastic volatility models with fat-tails and correlated errors显示文摘 | Eric Jacquier Nicholas G. Polson Peter E. Rossi | 2003 | Journal of Econometrics2003，，1： | 2 |
| 16 | Bayesian Analysis of Stochastic Volatility Models显示文摘 | Eric Jacquier Nicholas G Polson Peter E Rossi | 2002 | Journal of Business & Economic Statistics2002，，1： | 2 |
| 17 | GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications显示文摘 | Peter Bytzer Nicholas J Talley Johann Hammer Lisa J Young Michael P Jones Michael Horowitz | 2002 | The American Journal of Gastroenterology2002，，3： | 2 |
| 18 | American Gastroenterological Association Medical Position Statement on the Management of Gastroesophageal Reflux Disease显示文摘 | Peter J. Kahrilas Nicholas J. Shaheen Michael F. Vaezi | 2008 | Gastroenterology2008，，4： | 2 |
| 19 | The Relative Antioxidant Activities of Plant-Derived Polyphenolic Flavonoids显示文摘 | Catherine A. Rice-evans Nicholas J. Miller Paul G. Bolwell Peter M. Bramley John B. Pridham | 1995 | Free Radical Research1995，，4： | 2 |
| 20 | Post-harvest food losses in a maize-based farming system of semi-arid savannah area of Tanzania显示文摘 | Adebayo B. Abass Gabriel Ndunguru Peter Mamiro Bamidele Alenkhe Nicholas Mlingi Mateete Bekunda | 2013 | Journal of Stored Products Research2013，，： | 2 |
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