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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 | People and computers-some recent highlights显示文摘 | SHACKEL B | 2000 | Applied Ergonomics2000，31，： | 1 |
| 3 | The assessment of chair comfort显示文摘 | Shackel B Chidsey K D Shipley P | 1969 | Ergonomics1969，12，2： | 1 |
| 4 | 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 |
| 5 | Note on mobile eye viewpoint recording显示文摘 | Shackel B | 1960 | Journal of the Optical Society of America1960，50，8： | 1 |
| 6 | The assessment of chair comfort显示文摘 | SHACKEL B CHIDSEY K D SHIPLEY P | 1969 | Ergonomics1969，12，2： | 1 |
| 7 | The Assessment of chair Comfort 显示文摘 | SHACKEL B CHIDSEY K D SHIPLEY P | 1969 | Ergonomics1969，12，： | 1 |
| 8 | Usability- Context, Framework, Definition, Design and Evaluation显示文摘 | Shackel B | 2009 | Interacting with Computers2009，21，56： | 1 |
| 9 | Copper-salicylate gel for pain relief in osteoarthritis: a randomized controlled trial显示文摘 | Shackel NA Day RO Kellet B Books PM | 1997 | Med J Aust1997，167，3： | 1 |
| 10 | The design of interlocking concrete block pavements for road traffic显示文摘 | SHACKEL B | 1981 | Concrete Block Paving1981，，： | 1 |
| 11 | The assessment of chair comfort 显示文摘 | Shackel B hidsey K D Shipley P | 1969 | Ergonomics1969，12，2： | 1 |
| 12 | Usability-Context, framework, definition, design and evaluation 显示文摘 | Shackel B | 2009 | Interacting with Computers2009，，21： | 1 |
| 13 | The assessment of chair comfort显示文摘 | Shackel B Chidsey KD | 1969 | Ergonomics1969，12，： | 1 |
| 14 | Evaluating User computer In- teraction:A Framework显示文摘 | Sweeney M Maguire M Shackel B | 1993 | Intematicoial Journal of Man - Machine Studies1993，38，4： | 1 |
| 15 | EvaluatingUser - com- puter Interaction : A Framework 显示文摘 | Sweeney M Maguire M Shackel B | 1993 | International Journal of Man-MachineStudies1993，38，4： | 1 |
| 16 | Dispersal of early life stage haddock (Melanogrammus aeglefinus) as in- ferred from the spatial distribution and variability in length-at-age of juveniles 显示文摘 | Shackell N Frank K Petrie B | 1999 | Canadian Journal of Fish- eries and Aquatic Sciences1999，56，： | 1 |
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