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Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX
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《医学前沿(英文)》 2016年 第10卷 第2期 页码 212-218 doi: 10.1007/s11684-016-0438-y
Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5×1011 and 1×1011 virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B.
关键词: hemophilia B AAV8 hFIX gene therapy
Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B
null
《医学前沿(英文)》 2015年 第9卷 第1期 页码 90-99 doi: 10.1007/s11684-015-0390-2
Gene therapy provides a potential cure for hemophilia B, and significant progress has been achieved in liver-directed gene transfer mediated by adeno-associated viral vectors. Recent clinical trials involving the use of a self-complementary adeno-associated virus serotype 8-human codon-optimized factor IX (AAV8-hFIXco) vector demonstrated encouraging efficacy with hFIX expression stabilized at 1% to 6% of normal level in patients, but safety concerns related to high vector doses are still present. Thus, further improvement of AAV vectors and hFIX expression cassette may positively contribute to the ultimate success of hemophilia B gene therapy. In this study, to obtain a higher expression level of hFIX that potentiates the coagulant capacity of recipients, human FIX expression vector was optimized by upgrading the codon adaption index and adjusting the GC content, inserting a Kozak sequence (GCCACC), and introducing a gain-of-function mutation, R338L (FIX Padua). The efficiency of the published and the presently constructed cassettes was compared through in vivo screening. In addition, the regulatory elements that control the FIX gene expression in these cassettes were screened for liver-specific effectiveness. Among all the constructed cassettes, scAAV-Pre-hFIXco-SIH-R338L, which was the construct under the control of the prothrombin enhancer and prealbumin promoter, resulted in the highest level of coagulant activity, and the expression levels of two constructed cassettes (scAAV-Chi-hFIXco-SIH-R338L and scAAV-Pre-hFIXco-SIH-R338L) were also higher than that of the published cassette (scAAV-LP1-hFIXco-SJ). In summary, our strategies led to a substantial increase in hFIX expression at the protein level or a remarkably elevated coagulant activity. Thus, these reconstructs of hFIX with AAV vector may potentially contribute to the creation of an efficacious gene therapy of hemophilia B.
关键词: factor IX hemophilia B liver-specific regulatory elements hydrodynamic gene transfer
《医学前沿(英文)》 2022年 第16卷 第4期 页码 584-595 doi: 10.1007/s11684-021-0844-7
关键词: hemophilia A adeno-associated virus (AAV) human/rat hybrid factor VIII gene therapy dual chain strategy
Current hepatitis B treatment guidelines and future research directions
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《医学前沿(英文)》 2014年 第8卷 第2期 页码 145-157 doi: 10.1007/s11684-014-0335-1
Hepatitis B virus (HBV) infection causes a tremendous clinical burden across the world with more than half a million people dying annually from HBV related disease. Significant advances have been made in HBV treatment in the past decade and several guidelines have been published by professional societies and expert panels. Although these recommendations have been valuable to help optimize HBV treatment, there is discordance in treatment criteria and many patients infected with HBV may fall outside of these recommendations. This paper systematically reviews the natural history of the disease and compares and contrasts the recommendations for initiation of treatment from the various societies. There is also discussion of special groups that require particular consideration and some of the open research questions and future research directions within the field.
关键词: chronic hepatitis B HBV treatment guidelines APASL guidelines EASL guidelines AASLD guidelines
《医学前沿(英文)》 2022年 第16卷 第1期 页码 111-125 doi: 10.1007/s11684-021-0854-5
关键词: COVID-19 chronic hepatitis B liver injury coagulation dysfunction
Vaccine therapies for chronic hepatitis B: can we go further?
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《医学前沿(英文)》 2014年 第8卷 第1期 页码 17-23 doi: 10.1007/s11684-014-0313-7
Chronic hepatitis B is a major health burden worldwide. In addition to the recent progress in antiviral treatment, therapeutic vaccination is a promising new strategy for the control of chronic hepatitis B. On the basis of the major specific and non-specific immune dysregulations and defects in chronic hepatitis B patients, this paper presents the peptide and protein-based, DNA-based, cell-based, and antigen-antibody-based therapeutic vaccines, which have undergone clinical trials. The advantages, disadvantages, and future perspectives for these therapeutic vaccines are discussed.
关键词: chronic hepatitis B therapeutic antigen-antibody complexes DNA vaccine
Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China
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《医学前沿(英文)》 2014年 第8卷 第2期 页码 135-144 doi: 10.1007/s11684-014-0331-5
Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.
李伟,李强,王平
《中国工程科学》 2011年 第13卷 第1期 页码 56-61
基于概率断裂力学对B级钢货车侧架的圆角细节进行了模拟耐久性试验研究,提出了一种新的通用当量初始缺陷尺寸分布的计算方法,建立了裂纹超越概率模型
Impact analysis of compressor rotor blades of an aircraft engine
Y B SUDHIR SASTRY, B G KIROS, F HAILU, P R BUDARAPU
《结构与土木工程前沿(英文)》 2019年 第13卷 第3期 页码 505-514 doi: 10.1007/s11709-018-0493-3
关键词: axial flow compressor rotor and stator blades aircraft engine stress and impact analysis aluminum alloys
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《医学前沿(英文)》 2014年 第8卷 第2期 页码 250-253 doi: 10.1007/s11684-014-0333-3
The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery.
关键词: acute-on-chronic liver failure submassive necrosis viral hepatitis B esophageal variceal bleeding liver transplantation
带约束条件的C-Bézier曲面最优降多阶逼近 Article
Lian ZHOU, Xin-hui LIN, Hong-yan ZHAO, Jun CHEN
《信息与电子工程前沿(英文)》 2017年 第18卷 第12期 页码 2009-2016 doi: 10.1631/FITEE.1700458
关键词: C-Bézier曲面;降阶;边界约束
MicroRNA-148b promotes proliferation of hair follicle cells by targeting
Wanbao YANG,Qinqun LI,Bo SU,Mei YU
《农业科学与工程前沿(英文)》 2016年 第3卷 第1期 页码 72-80 doi: 10.15302/J-FASE-2016089
Correlation between viral load and liver cirrhosis in chronic hepatitis B patients
Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,
《医学前沿(英文)》 2009年 第3卷 第3期 页码 271-276 doi: 10.1007/s11684-009-0054-1
Geqing XIA MD, Zehua WANG MD, Li ZOU MD, Chaoying WU MS, Yu HU MD,
《医学前沿(英文)》 2010年 第4卷 第2期 页码 235-240 doi: 10.1007/s11684-010-0002-0
标题 作者 时间 类型 操作
Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B
null
期刊论文
Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed
期刊论文
Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center
期刊论文
Impact analysis of compressor rotor blades of an aircraft engine
Y B SUDHIR SASTRY, B G KIROS, F HAILU, P R BUDARAPU
期刊论文
Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report
null
期刊论文
MicroRNA-148b promotes proliferation of hair follicle cells by targeting
Wanbao YANG,Qinqun LI,Bo SU,Mei YU
期刊论文
Correlation between viral load and liver cirrhosis in chronic hepatitis B patients
Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,
期刊论文