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病毒性肝炎:乙型肝炎和丁型肝炎-临床(治疗、新化合物、耐药性) 一项在HBeAg阴性、慢性乙型肝炎(CHB)患者中比较磷丙替诺福韦(TAF)与富马酸替诺福韦二吡呋酯(TDF)的3期研究:96周时疗效和安全性结果

第九届全国疑难及重症肝病大会

作者： Kosh Agarwal Scott Fung Wai Kay Seto Young Suk lim Ed Gane harry l.janssen Manoj Sharma Wan long Chuang Ho Bae Ki Tae Yoon John F.Flaherty Audrey lau Anuj Gaggar Vithika Suri Andrea Cathcart lanjia lin G Mani Subramanian Shalimar Norihiro Furusyo Maria Buti Henry l.Chan Kings College Hospital Department of Medicine University of Toronto Queen Mary Hospital Hong Kong Asan Medical Center Kaohsiung Medical University Hospital Pusan National University Yangsan Hospital All India Institute of Medical Sciences Kyushu Medical Center The Chinese University of Hong Kong

背景和目的:TAF是替诺福韦(TFV)的一种新型前体药,在血浆中比TDF更稳定,增强了TFV进入肝细胞的给药,且循环TFV水平降低。这项针对HBeAg阳性患者的随机双盲研究显示,之前在48周时,在HBV DNA小于29IU/ml的患者比例方面,TAF的疗效并不劣于T...

背景和目的:TAF是替诺福韦(TFV)的一种新型前体药,在血浆中比TDF更稳定,增强了TFV进入肝细胞的给药,且循环TFV水平降低。这项针对HBeAg阳性患者的随机双盲研究显示,之前在48周时,在HBV DNA小于29IU/ml的患者比例方面,TAF的疗效并不劣于TDF,且骨骼和肾脏影响改善。本文摘展示了96周治疗后的结果。

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病毒性肝炎:乙型肝炎和丁型肝炎-临床(治疗、新化合物、耐药性) ...

Telaprevir/boceprevir era: From bench to bed and back

第九届全国疑难及重症肝病大会

作者： Maurizia Brunetto Young Suk lim Ed Gane Wai Kay Seto Marina Osipenko Sang Hoon Ahn harry l.janssen Akash Shukla Wan long Chuang Huy Trinh Mustafa K.Celen John F.Flaherty Audrey H.lau Anuj Gaggar Vithika Suri Neeru Bhardwaj Kyungpil Kim G Mani Subramanian Calvin Pan Namiki Izumi Patrick Marcellin Henry Chan Maria Buti University Hospital of Pisa Asan Medical Centre Erasmus Medical Center

背景和目的:TAF是替诺福韦(TFV)的一种新型前体药,在血浆中比TDF更稳定,增强了TFV进入肝细胞的给药,且循环TFV水平降低。这项在HBeAg阴性患者中比较TAF与TDF的随机双盲研究显示,之前在48周时,在HBV DNA小于29IU/ml的患者比例方面,TAF的...

背景和目的:TAF是替诺福韦(TFV)的一种新型前体药,在血浆中比TDF更稳定,增强了TFV进入肝细胞的给药,且循环TFV水平降低。这项在HBeAg阴性患者中比较TAF与TDF的随机双盲研究显示,之前在48周时,在HBV DNA小于29IU/ml的患者比例方面,TAF的疗效并不劣于TDF,且骨骼和肾脏影响改善。本文摘展示了96周治疗后的结果。方法:425例患者被随机分配到接受TAF 25mg QD(n=285)或TDF 300mg QD(n=140),且治疗144

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World Journal of Gastroenterology 2012年第43期18卷 6183-6188页

作者： Maikel P Peppelenbosch harry lA janssen Robert J de Knegt Department of Gastroenterology and Hepatology Erasmus MC-University Medical Center 3015 CE Rotterdam The Netherlands

Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.

关键词： Telaprevir Boceprevir Mechanism-of-action Clinical efficacy liver transplantation patient Interferon Ribavirin

Propulsive matrix of a helical flagellum

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Chinese Physics B 2014年第11期23卷 51-56页

作者：张何朋刘斌 Bruce Rodenborn harry l.Swinney Department of Physics and Astronomy and Institute of Natural Sciences School of Natural Sciences University of California Department of Physics and Center for Nonlinear Dynamics University of Texas at Austin

We study the propulsion matrix of bacterial flagella numerically using slender body theory and the regularized Stokeslet method in a biologically relevant parameter regime. All three independent elements of the matrix are measured by computing propulsive force and torque generated by a rotating flagellum, and the drag force on a translating flagellum. Nu- merical results are compared with the predictions of resistive force theory, which is often used to interpret micro-organism propulsion. Neglecting hydrodynamic interactions between different parts of a flagellum in resistive force theory leads to both qualitative and quantitative discrepancies between the theoretical prediction of resistive force theory and the numerical results. We improve the original theory by empirically incorporating the effects of hydrodynamic interactions and propose new expressions for propulsive matrix elements that are accurate over the parameter regime explored.

关键词： low-Reynolds-number flows micro-organism dynamics bacterial swimming

New therapeutic opportunities for Hepatitis C based on small RNA

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World Journal of Gastroenterology 2007年第33期13卷 4431-4436页

作者： Qiu-wei Pan Scot D Henry Bob J Scholte Hugo W Tilanus harry lA janssen luc JW van der laan Departments of Gastroenterology & Hepatology and Surgery Erasmus MC-University Medical Centre Rotterdam The Netherlands Department of Surgery Erasmus MC-University Medical Centre Rotterdam The Netherlands Department of Cell Biology Erasmus MC- University Medical Centre Rotterdam The Netherlands Department of Gastroenterology & Hepatology Erasmus MC-University Medical Centre Rotterdam The Netherlands

Hepatitis C virus （HCV） infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, antisense oligonucleotides （ASO）, or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA （miR-222） in viral replication and discuss its potential for HCV molecular therapy.

关键词： Hepatitis C virus therapy miR-122 RNAi Antisense oligonucleotides Viral vectors

The omnivorous predator Macrolophus pygmaeus,a good candidate for the control of both greenhouse whitefly and poinsettia thrips on gerbera plants

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Insect Science 2020年第3期27卷 510-518页

作者： Ada leman Barbara l.Ingegno luciana Tavella Arne janssen Gerben J.Messelink Wageningen University&Research Business Unit Greenhouse HorticultureBleiswijkthe Netherlands Dipartimento di Scienze Agrarie Forestall e Alimentari(DISAFA)ULF Entomologia Generate e ApplicataUniversity of TorinoGrugliasco(TO)Italy IBED Department of Evolutionary and Population BiologyUniversity of AmsterdamAmsterdamthe Netherlands

The poinsettia thrips Echinothrips americanus Morgan is a relatively new pest that has spread rapidly worldwide and causes serious damage in both vegetable and ornamental *** this study,we investigated if and how effective this pest can be controlled in gerbera by the omnivorous predator Macrolophus pygmaeus(Rambur).Because herbivores on plants can interact through a shared predator,we also investigated how poinsettia thrips control is affected by the presence of the greenhouse whitefly Trialeurodes vaporariorum(Westwood),a pest that commonly coexists with *** in *** laboratory studies,we found that the predator *** fed on both pests when offered *** tests showed a clear preference of the predators for plants infested by whiteflies but not by *** a greenhouse experiment,densities of both pests on single gerbera plants were reduced to very low levels by the predator,either with both pests present together or ***,predator‐mediated effects between whiteflies and thrips played only a minor *** plant feeding of the shared predator probably reduced the dependence of predator survival and reproduction on the densities of the two pests,thereby weakening potential predator‐mediated ***,*** is a good candidate for biological control of both pests in ***,further research is needed to investigate pest control at larger scales,when the pests can occur on different plants.

关键词： apparent competition biological control Echinothrips americanus pest interactions prey preference Trialeurodes vaporariorum

Hydroxycitric acid does not promote inflammation or liver toxicity

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World Journal of Gastroenterology 2013年第44期19卷 8160-8162页

作者： Dallas l Clouatre harry G Preuss Glykon Technologies Group LLC SeattleWA 98109 United States Department of Physiology Georgetown University Medical Center Washington DC 20057 United States

Garcinia cambogia extract(GC)with its active component consisting of hydroxycitric acid(HCA)is widely utilized for weight *** HCA salts are available,including calcium,magnesium,potassium and mixtures of ***,these salts exhibit different properties with some,but not all,improving glucose tolerance and blood ***,obesity-prone C57Bl/6J mice were fed a high-fat diet(HFD,45 kcal%fat)with or without GC(1%,w/w)for 16 *** active arm reduced visceral fat,adipocyte size and serum glucose,yet purportedly also exhibited hepatic collagen accumulation,lipid peroxidation and increased mRNA levels of genes related to oxidative *** latter findings are at odds with a large body of animal and human studies that have been conducted on the safety and efficacy of *** literature shows HCA to be protective against the liver toxicity associated with ethanol and dexamethasone administration,and to maintain serum aspartate aminotransferase,alanine aminotransferase and alkaline phosphatase at near normal *** both animal and clinical literature,elevated intakes of HCA per se have not led to signs of inflammation or *** compound has been found to reduce markers of inflammation in brain,intestines,kidney and serum.

关键词： Garcinia cambogia Hepatic collagen Hepatic inflammation Hepatic oxidative stress Hydroxycitric acid Metabolic syndrome Tumor necrosis factor-α Weight loss

Critical flow-storm approach to total maximum daily load (TMDl) development:an analytical conceptual model

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Frontiers of Environmental Science & Engineering 2008年第3期2卷 267-273页

作者： harry X.ZHANG Shaw l.YU CH2M HIll 15010 Conference Center DriveChantillyVA 20151–3801USA Department of Civil and Environmental Engineering Thornton HallUniversity of VirginiaCharlottesvilleVA 22904–4742USA

One of the key challenges in the total maximum daily load(TMDl)development process is how to define the critical condition for a receiving *** main concern in using a continuous simulation approach is the absence of any guarantee that the most critical condition will be captured during the selected representative hydrologic period,given the scarcity of long-term continuous *** objectives of this paper are to clearly address the critical condition in the TMDl development process and to compare continuous and event-based approaches in defining critical condition during TMDl development for a waterbody impacted by both point and nonpoint source pollution.A practical,event-based critical flow-storm(CFS)approach was developed to explicitly addresses the critical condition as a combination of a low stream flow and a storm event of a selected magnitude,both having certain frequencies of *** paper illustrated the CFS concept and provided its theoretical basis using a derived analytical conceptual *** CFS approach clearly defined a critical condition,obtained reasonable results and could be considered as an alternative method in TMDl development.

关键词： critical condition critical flow-storm(CFS)approach total maximum daily load(TMDl) conceptual model derived analytical model nonpoint source pollution

Bean yellow disorder virus： Parameters of transmission by Bemisia tabaci and host plant range

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Insect Science 2011年第1期18卷 50-56页

作者： German Martin Isabel Maria Cuadrado Dirk janssen Instituto Andaluz de Investigacion y Formacion Agraria y Pesquera Centro La Mojonera Almeria Spain

Bean yellow disorder virus （BnYDV） was recently identified as the first crinivirus （family Closteroviridae） that infects members of the family leguminosae. It was first observed during the autumn of 2003, causing heavy losses in French bean （Phaseolus vulgaris l.） grown commercially in Spain. The virus is transmitted by the sweetpotato whitefly, Bemisia tabaci （Hemiptera： Aleyrodidae） Q-biotype, and disease symptoms resemble nutritional disorders consisting of interveinal mottling and yellowing in leaves, combined with stiffness or brittleness, and are typically produced on the middle to lower parts of the plant. Transmission experiments showed that 50% and 100% of B. tabaci adults acquired the virus after a feeding period of 3 and 7 h, respectively. Viruliferous whiteflies infected 66% and 100% ofP. vulgaris plants after a feeding period of 12 and 24 h, respectively. The transmission efficiency of single whiteflies was 37% and persistence of BnYDV in the vector lasted up to 2 weeks with a half-life of 9 days. BnYDV was transmitted to P. vulgaris, Pisum sativum l., lens culinaris Medik., and Vicia faba l., but not to Vigna unguiculata l., Glycine max （l.） Merr., Cicer arietum l., and to crop species belonging to families of the Solanaceae and Cucurbitaceae. No virus was detected in field samples collected from 30 different species from Boraginaceae, Asteraceae, Geraniaceae, lamiaceae, leguminosae, Malvaceae, Scrophulariaceae, Thymelaeaceae and Verbenaceae. The restricted host range and efficient management of crops regarding whitefly infestation may be key elements in the control of BnYDV.

关键词： bean Closteroviridae Crinivirus disease vector whiteflies