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| 1 | Future prospectives for the management of chronic hepatitis B显示文摘Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately one million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load (HBV-DNA) plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory (interferons) and antiviral suppressants (nucleoside and nucleotide analogues) all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross- resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion: chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine thebest treatment for those failing treatment. | WF Leemans HLA Janssen RA de Man | 2007 | World Journal of Gastroenterology2007，13，18： | 14 |
| 2 | m TOR signaling in liver regeneration: Rapamycin combined with growth factor treatment显示文摘AIM: To investigate the effects of mammalian target of rapamycin(mT OR) inhibition on liver regeneration and autophagy in a surgical resection model.METHODS: C57BL/6 mice were subjected to a 70% partial hepatectomy(PH) and treated intraperitoneally every 24 h with a combination of the m TOR inhibitor rapamycin(2.5 mg/kg per day) and the steroid dexamethasone(2.0 mg/kg per day) in phosphate bufferedsaline(PBS) or with PBS alone as vehicle control. In the immunosuppressant group, part of the group was treated subcutaneously 4 h prior to and 24 h after PH with a combination of human recombinant interleukin 6(IL-6; 500 μg/kg per day) and hepatocyte growth factor(HGF; 100 μg/kg per day) in PBS. Animals were sacrificed 2, 3 or 5 d after PH and liver tissue and blood were collected for further analysis. Immunohistochemical staining for 5-Bromo-2'-deoxyuridine(Brd U) was used to quantify hepatocyte proliferation. Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3(LC3)-Ⅱ protein expression as a marker for autophagy. Hepatic gene expression levels of proliferation-, inflammation- and angiogenesisrelated genes were examined by real-time reverse transcription-polymerase chain reaction and serum bilirubin and transaminase levels were analyzed at the clinical chemical core facility of the Erasmus MC-University Medical Center.RESULTS: m TOR inhibition significantly suppressed regeneration, shown by decreased hepatocyte proliferation(2% vs 12% Brd U positive hepatocyte nuclei at day 2, P < 0.01; 0.8% vs 1.4% at day 5, P = 0.02) and liver weight reconstitution(63% vs 76% of initial total liver weight at day 3, P = 0.04), and furthermore increased serum transaminase levels(aspartate aminotransferase 641 U/L vs 185 U/L at day 2, P = 0.02). Expression of the autophagy marker LC3-Ⅱ, which was reduced during normal liver regeneration, increased after mT OR inhibition(46% increase at day 2, P = 0.04). Hepatic gene expression showed an increased inflammation-related response [tumor necrosis factor(TNF)-α 3.2-fold upregulation at day 2, P = 0.03; IL-1Ra 6.0-fold upregulation at day 2 and 42.3-fold upregulation at day 5, P < 0.01] and a reduced expression of cell cycle progression and angiogenesis-related factors(HGF 40% reduction at day 2; vascular endothelial growth factor receptor 2 50% reduction at days 2 and 5; angiopoietin 1 60% reduction at day 2, all P ≤ 0.01). Treatmentwith the regeneration stimulating cytokine IL-6 and growth factor HGF could overcome the inhibitory effect on liver weight(75% of initial total liver weight at day 3, P = 0.02 vs immunosuppression alone and P = 0.90 vs controls) and partially reversed gene expression changes caused by rapamycin(TNF-α and IL-1Ra levels at day 2 were restored to control levels). However, no significant changes in hepatocyte proliferation, serum injury markers or autophagy were found.CONCLUSION: mT OR inhibition severely impairs liver regeneration and increases autophagy after PH. These effects are partly reversed by stimulation of the IL-6 and HGF pathways. | Suomi MG Fouraschen Petra E de Ruiter Jaap Kwekkeboom Ron WF de Bruin Geert Kazemier Herold J Metselaar Hugo W Tilanus Luc JW van der Laan Jeroen de Jonge | 2013 | World Journal of Transplantation2013，3，3： | 6 |
| 3 | Intraoperative stimulation of pedicle sctews:A new method for verification of screw placement显示文摘 | Young WF Morledge DE Martin W | 1995 | Surg Neurol1995，44，： | 1 |
| 4 | Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy显示文摘 | Cooper ME De Zeeuw D Keane WF Mitch WE Parving H-H | 2001 | N Engl J Med2001，345，12： | 1 |
| 5 | Management of chest injuries-a 5 year retrospective survey 显示文摘 | Kalyanaraman R De Mello WF Ravishankar M | 1998 | Injury1998，29，6： | 1 |
| 6 | Exacerbation of chronic hepatitis B infection after delivery显示文摘 | Ter Borg MJ Leemans WF De Man RA | 2008 | Journal of Viral Hepatitis2008，15，1： | 1 |
| 7 | The risk ofdeveloping end-stage renal disease in patients with type 2 dia-betes and nephropathy: the RENAAL study 显示文摘 | KEANE WF BRENNER BM DE ZEEUW D | 2003 | Kidney Int2003，63，4： | 1 |
| 8 | Long-term inhalable particles and other air pollutants related to mortality in nonsmokers 显示文摘 | Abbey DE Nishino N McDonnell WF Burchette RJ Knutsen SF Lawrence Beeson W Yang JX | 1999 | Am J Respir Crit Care1999，159，2： | 1 |
| 9 | Relationships of mortality with the fine and coarse fractions of long-term ambient PMI0 concentrations in nonsmokers 显示文摘 | McDonnell WF Nishino-Ishikawa N Petersen FF Chen LH Abbey DE | 2000 | J Expo Anal Environ Epidemiol2000，10，5： | 1 |
| 10 | Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation显示文摘 | Tonino PA Fearon WF De Bruyne B | 2010 | J Am Coil Cardiol2010，55，25： | 1 |
| 11 | The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy:the RENAAL study显示文摘 | Keane WF Brenner BM de Zeeuw D | | 0，，： | 1 |
| 12 | The major genetic determinants of HIV-1control affect HLA class I peptide presentation显示文摘 | International HIV Controllers Study Pereyra F Jia X McLaren P J Telenti A de Bakker P I Walker B D Ripke S Brumme C J Pulit S L Carrington M Kadie C M Carlson J M Heckerman D Graham R R Plenge R M Deeks S G Gianniny L Crawford G Sullivan J Gonzalez E Davies L Camargo A Moore JM Beattie N Gupta S Crenshaw A Burtt N P Guiducci C Gupta N Gao X Qi Y Yuki Y Piechocka-Trocha A Cutrell E Rosenberg R Moss K L Lemay P O'Leary J Schaefer T Verma P Toth I Block B Baker B Rothchild A Lian J Proudfoot J Alvino D M Vine S Addo M M Allen T M Altfeld M Henn M R Le Gall S Streeck H Haas D W Kuritzkes D R Robbins G K Shafer R W Gulick R M Shikuma C M Haubrich R Riddler S Sax P E Daar E S Ribaudo H J Agan B Agarwal S Ahern R L Allen B L Altidor S Altschuler E L Ambardar S Anastos K Anderson B Anderson V Andrady U Antoniskis D Bangsberg D Barbaro D Barrie W Bartczak J Barton S Basden P Basgoz N Bazner S Bellos N C Benson A M Berger J Bernard N F Bernard A M Birch C Bodner S J Bolan R K Boudreaux E T Bradley M Braun J F Brndjar J E Brown S J Brown K Brown S T Burack J Bush LM Cafaro V Campbell O Campbell J Carlson R H Carmichael J K Casey K K Cavacuiti C Celestin G Chambers S T Chez N Chirch L M Cimoch P J Cohen D Cohn LE Conway B Cooper D A Cornelson B Cox D T Cristofano M V Cuchural G Jr Czartoski J L Dahman J M Daly J S Davis B T Davis K Davod S M DeJesus E Dietz C A Dunham E Dunn M E Ellerin T B Eron J J Fangman J J Farel C E Ferlazzo H Fidler S Fleenor-Ford A Frankel R Freedberg K A French N K Fuchs JD Fuller J D Gaberman J Gallant J E Gandhi R T Garcia E Garmon D Gathe J C Jr Gaultier C R Gebre W Gilman F D Gilson I Goepfert P A Gottlieb M S Goulston C Groger R K Gurley T D Haber S Hardwicke R Hardy W D Harrigan P R Hawkins T N Heath S Hecht F M Henry W K Hladek M Hoffman R P Horton J M Hsu R K Huhn G D Hunt P Hupert M J Illeman M L Jaeger H Jellinger R M John M Johnson J A Johnson K L Johnson H Johnson K Joly J Jordan W C Kauffman C A Khanlou H Killian R K Kim A Y Kim D D Kinder C A Kirchner J T Kogelman L Kojic E M Korthuis P T Kurisu W Kwon D S LaMar M Lampiris H Lanzafame M Lederman M M Lee D M Lee J M Lee M J Lee E T Lemoine J Levy J A Llibre J M Liguori M A Little S J Liu A Y Lopez A J Loutfy M R Loy D Mohammed D Y Man A Mansour M K Marconi V C Markowitz M Marques R Martin J N Martin H L Jr Mayer K H McElrath M J McGhee T A McGovern B H McGowan K McIntyre D Mcleod GX Menezes P Mesa G Metroka CE Meyer-Olson D Miller A O Montgomery K Mounzer K C Nagami E H Nagin I Nahass R G Nelson M O Nielsen C Norene D L O'Connor D H Ojikutu B O Okulicz J Oladehin O O Oldfield E C Olender S A Ostrowski M Owen WF Jr Pae E Parsonnet J Pavlatos A M Perlmutter A M Pierce M N Pincus J M Pisani L Price L J Proia L Prokesch R C Pujet H C Ramgopal M Rathod A Rausch M Ravishankar J Rhame F S Richards C S Richman D D Rodes B Rodriguez M Rose R C 3rd Rosenberg E S Rosenthal D Ross P E Rubin D S Rumbaugh E Saenz L Salvaggio M R Sanchez WC Sanjana V M Santiago S Schmidt W Schuitemaker H Sestak P M Shalit P Shay W Shirvani V N Silebi V I Sizemore J M Jr Skolnik P R Sokol-Anderson M Sosman J M Stabile P Stapleton J T Starrett S Stein F Stellbrink H J Sterman FL Stone V E Stone D R Tambussi G Taplitz R A Tedaldi E M Telenti A Theisen W Torres R Tosiello L Tremblay C Tribble M A Trinh P D Tsao A Ueda P Vaccaro A Valadas E Vanig T J Vecino I Vega V M Veikley W Wade B H Walworth C Wanidworanun C Ward D J Warner D A Weber R D Webster D Weis S Wheeler D A White D J Wilkins E Winston A Wlodaver C G van't Wout A Wright D P Yang O O Yurdin D L Zabukovic B W Zachary K C Zeeman B Zhao M | 2010 | Science2010，330，6010： | 1 |
| 13 | Angiographic versus functional serversity of coronary artery stenosis in the FAME study fractional flow reserve versus angiography in multivessel cvlauation 显示文摘 | Tonino PA Fearon WF De Bruyne B | 2010 | J Am Coll Cariol2010，55，25： | 1 |
| 14 | Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography inmultivessel evaluation显示文摘 | Tonino PA Fearon WF De Bruyne B | 2010 | J Am Coil Cardiol2010，55，25： | 1 |
| 15 | Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol显示文摘 | de Azevedo WF Jr Canduri F da Silveira NJ | 2002 | Biochem Biophys Res Commun2002，293，： | 1 |
| 16 | The pathophysiology and clinical course of the normal coronary angina syndrome (car- diac syndrome X) 显示文摘 | Melikian N De Bruyne B Fearon WF | 2008 | Prog Cardiovasc Dis2008，50，4： | 1 |
| 17 | Intraoperative stimulation ofpedicle screws: A new method /'or verification of screw place- ment显示文摘 | Young WF Morledge DE | 1995 | Surgical Neurology1995，44，6： | 1 |
| 18 | Fractional flowreserve-guided PCI for stable coronary artery disease 显示文摘 | De Bruyne B Fearon WF Pijls NH | 2014 | N EnglJ Med2014，371，： | 1 |
| 19 | The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study显示文摘 | Keane WF Brenner BM de Zeeuw D | 2003 | Kid- ney 1nt2003，63，4： | 1 |
| 20 | Cardiac troponin and outcome in acute heart failure 显示文摘 | Peacock WF 4th De Marco T Fonarow GC | 2008 | N Engl J Med2008，358，20： | 1 |
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