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《医学前沿（英文）》 页码 878-888 doi: 10.1007/s11684-023-0993-y
关键词： uveal melanoma liver-directed therapy immune checkpoint blockade SIRT anti-PD-1 anti-CTLA-4
Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B
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《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
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《医学前沿（英文）》 2015年 第9卷 第2期 页码 187-219 doi: 10.1007/s11684-015-0386-y
Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte-specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.
关键词： autoimmune hepatitis autoantibodies diagnosis immunological diseases drug-induced liver injury therapy immunosuppression outcomes hepatocellular carcinoma liver transplantation
蒋国梁
《中国工程科学》 2009年 第11卷 第10期 页码 129-136
报告三维适形（3-dimensional conformal radiation therapy, 3DCRT）和调强放疗（intensity-modulatedradiation therapy, IMRT）治疗原发性肝癌（HCC）的基础和临床研究,建立了3DCRT和IMRT放疗HCC的技术，进行3个临床试验，获得了令人鼓舞的3年总生存率：28 ％～33 ％
Advances in the study of directed evolution for cellulases
Hailong LIN, Weiguang LI, Changhong GUO, Sihang QU, Nanqi REN
《环境科学与工程前沿（英文）》 2011年 第5卷 第4期 页码 519-525 doi: 10.1007/s11783-011-0326-2
关键词： biohydrogen bioethanol cellulase cellulose directed evolution
Unnormalized and normalized forms of gefura measures in directed and undirected networks
Raf GUNS,Ronald ROUSSEAU
《信息与电子工程前沿（英文）》 2015年 第16卷 第4期 页码 311-320 doi: 10.1631/FITEE.1400425
关键词： Networks subdivided in groups Partitions Gefura measures Q-measures Brokerage role Directed and undirected networks Brandes’ algorithm
Controllability analysis of second-ordermulti-agent systemswith directed andweighted interconnection
Di GUO,Rong-hao ZHENG,Zhi-yun LIN,Gang-feng YAN
《信息与电子工程前沿（英文）》 2015年 第16卷 第10期 页码 838-847 doi: 10.1631/FITEE.1500069
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《医学前沿（英文）》 2011年 第5卷 第1期 页码 1-7 doi: 10.1007/s11684-010-0105-7
Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.
关键词： partial liver transplantation reduced-size liver transplantation split liver transplantation living donor liver transplantation
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《医学前沿（英文）》 2018年 第12卷 第3期 页码 262-268 doi: 10.1007/s11684-017-0584-x
γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.
关键词： γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration
《化学科学与工程前沿（英文）》 2022年 第16卷 第5期 页码 699-708 doi: 10.1007/s11705-021-2093-3
关键词： layer-by-layer self-assembly single bilayer nanofiltration membrane desalination
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《医学前沿（英文）》 2018年 第12卷 第3期 页码 249-261 doi: 10.1007/s11684-018-0622-3
Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.
关键词： natural killer T cells hepatitis B virus and hepatitis C virus infection autoimmune liver diseases alcoholic liver disease nonalcoholic fatty liver disease hepatocellular carcinoma
Natural killer cells in liver diseases
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《医学前沿（英文）》 2018年 第12卷 第3期 页码 269-279 doi: 10.1007/s11684-018-0621-4
The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.
关键词： natural killer cell phenotype immune activation immune tolerance liver diseases
Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu
《医学前沿（英文）》 2021年 第15卷 第3期 页码 495-505 doi: 10.1007/s11684-020-0790-9
关键词： hepatitis B virus-related liver failure traditional Chinese medicine liver regeneration liver regeneration microenvironment cytokines
Assessment of liver volume variation to evaluate liver function
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《医学前沿（英文）》 2012年 第6卷 第4期 页码 421-427 doi: 10.1007/s11684-012-0223-5
In order to assess the value of liver volumetry in cirrhosis and acute liver failure (ALF) patients, we explored the correlation between hepatic volume and severity of the hepatic diseases. The clinical data of 48 cirrhosis patients with 60 normal controls and 39 ALF patients were collected. Computed tomography-derived liver volume (CTLV) and body surface area (BSA) of normal controls were calculated to get a regression formula for standard liver volume (SLV) and BSA. Then CTLV and SLV of all patients were calculated and grouped by Child-Turcotte-Pugh classification for cirrhosis patients and assigned according to prognosis of ALF patients for further comparison. It turned out that the mean liver volume of the control group was 1 058±337 cm3. SLV was correlated with BSA according to the regression formula. The hepatic volume of cirrhosis patients in Child A, B level was not reduced, but in Child C level it was significantly reduced with the lowest liver volume index (CTLV/SLV). Likewise, in the death group of ALF patients, the volume index was significantly lower than that of the survival group. Based on volumetric study, we proposed an ROC (receiver operating characteristic) analysis to predict the prognosis of ALF patients that CTLV/SLV<83.9% indicates a poor prognosis. In conclusion, the CTLV/SLV ratio, which reflects liver volume variations, correlates well with the liver function and progression of cirrhosis and ALF. It is also a very useful marker for predicting the prognosis of ALF.
关键词： liver volume variation cirrhosis acute liver failure (ALF)
Gut microbial balance and liver transplantation: alteration, management, and prediction
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《医学前沿（英文）》 2018年 第12卷 第2期 页码 123-129 doi: 10.1007/s11684-017-0563-2
Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.
关键词： gut microbial balance liver transplantation ischemia–reperfusion acute rejection
标题 作者 时间 类型 操作
Liver-directed treatment is associated with improved survival and increased response to immune checkpoint
期刊论文
Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B
null
期刊论文
Advances in the study of directed evolution for cellulases
Hailong LIN, Weiguang LI, Changhong GUO, Sihang QU, Nanqi REN
期刊论文
Unnormalized and normalized forms of gefura measures in directed and undirected networks
Raf GUNS,Ronald ROUSSEAU
期刊论文
Controllability analysis of second-ordermulti-agent systemswith directed andweighted interconnection
Di GUO,Rong-hao ZHENG,Zhi-yun LIN,Gang-feng YAN
期刊论文
Ionic strength directed self-assembled polyelectrolyte single-bilayer membrane for low-pressure nanofiltration
期刊论文
The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortalityof patients with hepatitis B-related liver failure based on real-world clinical data
Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu
期刊论文
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