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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 | Diabetes and Nonalcoholic Fatty Liver Disease: A Pathogenic Duo显示文摘 | K. H. Williams N. A. Shackel M. D. Gorrell S. V. McLennan S. M. Twigg | 2013 | Endocrine Reviews2013，，1： | 4 |
| 3 | East meets West: acute liver failure in the global village显示文摘 | Bowen DG Shackel NA Mccaughan GW | 2000 | J Gastroenterol Hepatol2000，15，5： | 1 |
| 4 | Insights into the pathobiology of hepatitis C virus-associated cirrhosis:analysis of intrahepatic differential gene expression显示文摘 | Shackel NA McGuinness PH Abbott CA | | 0，，02： | 1 |
| 5 | People and computers-some recent highlights显示文摘 | SHACKEL B | 2000 | Applied Ergonomics2000，31，： | 1 |
| 6 | Real-time reverse transcriptase- polymerase chain reaction (RT-PCR) for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBR Green Ⅰ显示文摘 | Yin JL Shackel NA Zekry A | 2001 | Immunol Cell Biol2001，79，3： | 1 |
| 7 | Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro显示文摘 | Wine J Jung C K Shackel I | 1999 | Anal Biochem1999，270，1： | 1 |
| 8 | Local identity, national memory, and heritage tourism: Creating a sense of place with archaeology显示文摘 | Shackel P A | 2005 | Illinois Antiquity2005，40，3： | 1 |
| 9 | The assessment of chair comfort显示文摘 | Shackel B Chidsey K D Shipley P | 1969 | Ergonomics1969，12，2： | 1 |
| 10 | 建立精益生产环境显示文摘将精益生产与简化的战略会计、价值流成本核算和可视化报告相结合,是精益实践取得成功的关键。Rosemary R.Fullerton、Frances A.Kennedy和Saly K.Widener三人所做的研究表明,精益生产和精益会计需要同时实施,才能确保企业进一步减少浪费、提高生产效率和财务控制水平,并最终为客户提供更好的服务。精益生产可以从精益管理会计环境的三方面受益。 | Phebian Davis Lydia Schleifer Margaret Shackell Sally K.Widener | 2020 | 新理财(公司理财)2020，0，6： | 1 |
| 11 | Boards, CEOs, and Surviving a Financial Crisis: Evidence from the Internet Shakeout 显示文摘 | DOWELL G W S SHACKELL M B STUART N V | 2011 | Strategic Management Journal2011，32，10： | 1 |
| 12 | Systematic review: the treatment of muscle cramps in patients with cirrhosis显示文摘 | H. Vidot S. Carey M. Allman‐Farinelli N. Shackel | 2014 | Aliment Pharmacol Ther2014，，3： | 1 |
| 13 | Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro 显示文摘 | Winer J Jung CK Shackel I | 1999 | Anal Biochem1999，270，1： | 1 |
| 14 | Artifical insemination of farmed red deer 显示文摘 | Fennessy P F Mackintosh C G Shackell G H | 1990 | Anita Production1990，51，： | 1 |
| 15 | Note on mobile eye viewpoint recording显示文摘 | Shackel B | 1960 | Journal of the Optical Society of America1960，50，8： | 1 |
| 16 | Development and Validation of Real-time Quantitative Reverse Transcriptase-polymerase Chain Reaction for Monitoring Gene Expression in Cardiac Myocytes in vitro显示文摘 | WINER J JUNG C SHACKEL K | 1999 | Anal Bioehem1999，270，1： | 1 |
| 17 | Real-time reverse transcriptasepolymerase chain reaction (RT-PCR) for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBR Green Ⅰ 显示文摘 | Yin J L Shackel N A Zekry A | 2001 | Immunol Cell Biol2001，79，3： | 1 |
| 18 | Real-time reverse transcriptase polymerase chain reaction(RT-PCT)for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBR Green I显示文摘 | Yin JL Shackel NA Zekry A | 2001 | Immunol Cell Biol2001，79，3： | 1 |
| 19 | Development and validation of real-time quantitative reverse transcriptase- polymerase chain reaction for monitoring gene expression in cardiac myoeytes in vitro显示文摘 | Winer J Jung C K Shackel I | 1999 | Anal Biochem1999，270，1： | 1 |
| 20 | Video push enteroscopy in the investigation of small bowel diseases:defining clinical indications and outcomes显示文摘 | Shackel NA Bowen DG Selby WS | 1998 | Aust N Z JMed1998，28，2： | 1 |
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