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A Novel Missense Mutation(L296Q)in Cholesteryl Ester Transfer Protein Gene Related to Coronary Heart Disease

Acta Biochimica et Biophysica Sinica 2004年第1期36卷 33-36页

作者： Ke-Qin ZHENG, Si-Zhong ZHANG, Li ZHANG, De-Jia HUANG, Lin-Chuan LIAO, and Yi-Ping HOU ( department of Medical Genetics, west china hospital Division of Human Morbid Genomics, Key Laboratory ofBiotherapy of Human Diseases of Ministry of Education, sichuan university, chengdu 610041, china department of cardiology, west china hospital, sichuan university, chengdu 610041, china School of Basic and Forensic Medicine, sichuan university, chengdu 610041, china) department of Medical Genetics West China Hospita Division of Human Morbid Genomics Key Laboratory of Biotherapy of Human Diseases of Ministry of Education Sichuan University Chengdu 610041 Chin

Cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport of cholesterol from the peripheral tissues to the liver. To understand the role that CETP gene plays in the pathogenesis of coronary heart disease (CHD) , the promoter region, all 16 exons and adjacent intronic regions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and 209 controls by a combination of PCR, denaturing high performance liquid chromatography (DHPLC), molecular cloning, and DNA sequencing. A novel missense mutation in the CETP gene was identified. This mutation (L296Q) was a T-to-A conversion at codon 296 of exon 10 which replaced the codon for leucine (CTG) with the codon for glutamine (CAG). Association study revealed that L296Q mutation was associated with CHD with a significantly higher mutant allele frequency in the CHD patients than that in the controls (0. 160 vs. 0.091,x2= 9.014, P = 0.003), and that the odds ratio for the development of CHD was 1.83 for

关键词： cholesteryl ester transfer protein gene (CETP gene) coronary heart disease (CHD) missense mutation plasma lipids single nucleoti.de polymorphism (SNP)

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肝脂酶基因A+884→G多态性及其与冠心病的相关性（英文）

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生物化学与生物物理学报 2003年第7期35卷 606-610页

作者：苏智广张思仲张立童煜肖翠英侯一平廖林川四川大学华西医院医学遗传室四川大学华西医院心血管内科四川大学华西医学中心基础与法医学院四川大学华西医学中心基础与法医学院成都610041

肝脂酶 (hepaticlipase ,HL)对血浆脂蛋白的代谢起重要作用 ,它影响着血浆中高密度脂蛋白 (HDL)的水平以及低密度脂蛋白 (LDL)的种类 ,因此肝脂酶的活性与冠心病的发生具有相关性。肝脂酶基因的单核苷酸多态性 (SNP)与酶的活性相关 ,并... 详细信息

肝脂酶 (hepaticlipase ,HL)对血浆脂蛋白的代谢起重要作用 ,它影响着血浆中高密度脂蛋白 (HDL)的水平以及低密度脂蛋白 (LDL)的种类 ,因此肝脂酶的活性与冠心病的发生具有相关性。肝脂酶基因的单核苷酸多态性 (SNP)与酶的活性相关 ,并影响血浆脂蛋白水平以及冠心病的发生。目前对肝脂酶基因多态性的研究多集中于启动子区。对该基因编码区的单核苷酸多态性与中国汉族冠心病的相关性进行研究。采用聚合酶链反应、变性高效液相色谱及DNA测序等技术对 10 2例经冠状动脉造影确诊的冠心病患者和 84例正常对照的肝脂酶基因编码区 (包括所有外显子及其侧翼序列 )的SNP进行了研究 ,结果在肝脂酶基因第 6外显子发现了一未见报道的多态位点 ,即A+884 →G转换 ,该碱基变异导致肝脂酶第 2 76位Lys被Arg取代。经检验 ,对照组和病例组基因型频率的分布符合Hardy Weinberg平衡。冠心病患者组中G+884 等位基因的携带者 (基因型为AG或GG)显著高于对照组 ( 5 4 .9%vs.4 1.5 % ,χ2 =6 .16 4 ,df=2 ,P =0 .0 4 6 ) ,且冠心病组中G+884 等位基因的频率显著高于对照组 ( 31.4 %vs .2 1.3% ,χ2 =4 .6 5 2 ,df=1,P =0 .0 31)。在肝脂酶基因启动子区发现了一个新的多态位点T- 2 →C ,该多态位点与冠心病的发生以及血浆高密度脂?

关键词：肝脂酶基因单核苷酸多态性连锁不平衡冠心病

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Visfatin upregulates the expression of monocyte chemotactic protein-1 via lectin-like oxidized low-density lipoprotein receptor-1 in vascular endothelial cells

Visfatin upregulates the expression of monocyte chemotactic ...

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中国生理学会心血管生理学术研讨会

作者： Xiaoyu Han~(1,2),Wenchao Wu~1,Qian Wang~1,Xiaoying Chen~(1,2),Xiaojing Liu~(1,2) 1.Laboratory of Cardiovascular Diseases,west china hospital,sichuan university 2.department of cardiology,west china hospital,sichuan university,chengdu 610041 china

＜正＞Background:Obesity is a major risk factor for the development of atherosclerosis,and atherosclerosis is recognized as a chronic inflammatory *** is identified as a novel visceral adipokine,which might be involved in obesity-related vascular diseases and ***-1,a receptor for ox-LDL（oxidized low-density lipoprotein）,has been implicated in ***,the potential link between Visfatin and LOX-1 has not been ***,whether visfatin could regulate LOX-1 expression in human umbilical vein endothelial cells（HUVECs） was investigated in this *** effect of blocking LOX-1 expression on the expression of monocyte chemotactic protein-1（MCP-1） was further ***:HUVECs were isolated from umbilical cords by collagenase digestion and cultured as previously ***-arrested HUVECs were treated with different concentrations of human recombinant Visfatin for different *** gene expression of LOX-1 and MCP-1 was analyzed by real-time RT-PCR,the protein expression of LOX-1 was assessed by western Blot and immnuocytochemistry,and the secretion of MCP-1 was measured by ***:Compare with untreated control groups,100ng/mL concentration of Visfatin could induce LOX-1 and MCP-1 mRNA and protein expression after 24 hours treatment in *** up-regulation of MCP-1 expression appears to be LOX-1-dependent since blockade of LOX-1 by its specific inhibitor polyinosinic acid inhibits the visfatin-induced MCP-1 gene and protein expression Conclusions:Our findings suggest for the first time that, visfatin could increase the gene expression and protein production of MCP-1 via LOX-1 in HUVECs,which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

关键词： Visfatin lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) monocyte chemotactic protein-1(MCP-1)

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氧化低密度脂蛋白对血管内皮细胞骨架的损伤及其机制

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心血管康复医学杂志 2004年第4期13卷 320-321,348页

作者：陈玉成梁玉佳刘瑞黄明慧曾智四川大学华西医院心内科四川成都610041 四川大学华西医院实验室四川成都610041

目的:观察氧化低密度脂蛋白(OxLDL)对血管内皮细胞(ECV-304)微丝肌动蛋白的影响及同细胞内钙离子变化间的关系,以探讨OxLDL的致动脉粥样硬化机制。方法:采用ECV 304内皮细胞株体外培养,分为空白对照组,OxLDL (200 μg/ml)组,采用激光扫... 详细信息

目的:观察氧化低密度脂蛋白(OxLDL)对血管内皮细胞(ECV-304)微丝肌动蛋白的影响及同细胞内钙离子变化间的关系,以探讨OxLDL的致动脉粥样硬化机制。方法:采用ECV 304内皮细胞株体外培养,分为空白对照组,OxLDL (200 μg/ml)组,采用激光扫描共聚显微镜分别观察OxLDL作用后12小时胞内钙离子的变化及OxLDL作用24小时后的细胞骨架微丝(F-actin)的改变。结果:OxLDL作用12小时后细胞内钙离子浓度明显升高(P<0.001),而F-actin也在24小后发生明显的破坏。结论:OxLDL可破坏内皮细胞的骨架结构从而导致血管内皮细胞的屏障功能的损害,这一作用可能与动脉粥样硬化形成有关。

关键词：氧化低密度脂蛋白血管内皮细胞损伤机制细胞骨架动脉粥样硬化

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Role of uterine natural killer cells in angiogenesis of human decidua of the first-trimester pregnancy

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Science china(Life Sciences) 2008年第2期51卷 111-119页

作者： LI GuoHua1, HUANG Wei1, XIA QingJie2, YANG KaiXuan3, LIU RaoFang1, ZHU HuiLi1 & JIANG Wei4 1 department of Reproductive Endocrinology, west china Second university hospital, sichuan university, chengdu 610041, china 2 west china Research Laboratory of Molecular Genetics, sichuan university, chengdu 610041, china 3 department of Pathology, west china Second university hospital, sichuan university, chengdu 610041, china 4 department of Pathology, west china hospital, sichuan university, chengdu 610041, china 1. department of Reproductive Endocrinology West China Second University Hospital Sichuan University Chengdu 610041 China 2. west china Research Laboratory of Molecular Genetics Sichuan University Chengdu 610041 China 3. department of Pathology West China Second University Hospital Sichuan University Chengdu 610041 China 4. department of Pathology West China Hospital Sichuan University Chengdu 610041 China

Decidualization is accompanied by extensive angiogenesis, which is an essential step in the maturation of new blood vessels in mammalian pregnancy. The purpose of this study was to determine a distribution of uNK cells (CD56+ uNK or CD56bright cells) in human decidua of the first-trimester pregnancy, and investigate whether uNK cells in human decidua could express vascular endothelial growth factor (VEGF-A) and/or angiopoietin2 (Ang2). Our immunohistochemical staining results demonstrated that a great amount of uNK (CD56+) cells scattered throughout the decidual stroma and near endometrial gland and spiral vessels in human decidua. The protein expression of VEGF-A and Ang2 was detected in decidual stroma cells, capillary endothelial cells and glandular cells in tissue specimens. There was a positive correlation between microvessel density (MVD) and the number of the CD56-positive uNK cells in decidual stroma, and also between the number of the CD56-positive uNK cells and VEGF-A protein expression in the tissue. In addition, we found that uNK cells in human decidua could express VEGF-A mRNA, but not Ang2 mRNA, in isolated uNK cells in human decidua of the first-trimester gestation by combination of LCM and Nested-PCR. Our study indicated that uNK cells, through expressing VEGF-A, may play an important role in the angiogenic response at the time of human decidualization and early placenta development.

关键词： uterine natural killer cells decidua angiogenesis VEGF Ang2

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Direct in vivo injection of ^(131)I-GMS and its distribution and excretion in rabbit

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World Journal of Gastroenterology 2010年第17期16卷 2120-2128页

作者： Yu Ma,Yi Wan,Li-Geng Duan,Xiao-Li Chen,The Research Unit of Hepato-Bilio-Pancreatology and department of Hepatic Surgery,west china hospital of sichuan university,chengdu 610041,sichuan Province,china Dong-Hui Luo,Chuan-Qin Xia,College of Chemistry,sichuan university,chengdu 610041,sichuan Province,china Lin Li,department of Nuclear Medicine and The National Key Discipline of Medical Imaging and Nuclear Medicine,west china hospital of sichuan university,chengdu 610041,sichuan Province,china The Research Unit of Hepato-Bilio-Pancreatology and department of Hepatic Surgery West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China. zean_z@***

AIM: To explore the distribution and metabolism of 131 I-gelatin microspheres ( 131 I-GMSs) in rabbits after direct injection into rabbits’ ***: Twenty-eight healthy New Zealand rabbits were divided into seven groups,with four rabbits per *** rabbit’s hepatic lobes were directly injected with 41.336 ± 5.106 MBq 131 *** day after 131 I-GMSs administration,4 rabbits were randomly selected,and 250 μL of serum was collected for γ *** and thyroid functions were tested on days 1,4,8,16,24,32,48 and 64 after 131 I-GMSs ***-photon emission computed tomography (SPECT) was taken for each group on days 0,1,4,8,16,24,32,48,64 after 131 I-GMSs administration.A group of rabbits were sacrificed respectively on days 1,4,16,24,32,48,64 after 131 I-GMSs *** livers were taken out for histological ***: After 131 I-GMSs administration,the nuclide was collected in the hepatic area with *** radiation could be detected on day 48 after 131 IGMSs administration,and radiography could be seen in thyroid areas in SPECT on days 4,8,16 and *** day after 131 I-GMSs administration,the liver function was damaged but recovered 4 d *** days after 131 I-GMSs administration,the levels of free triiodothyronine and free thyroxin were reduced,which restored to normal levels on day *** examination showed that the microspheres were degraded to different degrees at 24,32 and 48 d after 131 I-GMSs *** surrounding parts of injection points were in fibrous *** microspheres were detected in histological examination on day 64 after 131 I-GMSs ***: Direct in vivo injection of 131 I-GMSs is safe in *** may be a promising method for treatment of malignant tumors.

关键词： 131 I Label Gelatin microspheres Animal Rabbit Hepatic Direct injection

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Organ fibrosis inhibited by blocking transforming growth factor-β signaling via peroxisome proliferator-activated receptor γ agonists

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Hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 467-478页

作者： Yi-Lei Deng, Xian-Ze Xiong, Nan-Sheng Cheng department of General Surgery, west china hospital,sichuan university, chengdu 610041, china department of General Surgery West China Hospital Sichuan University Chengdu 610041 Chengdu China

BACKGROUND:Organ fibrosis has been viewed as one of the major medical problems, which can lead to progressive dysfunction of the liver, lung, kidney, skin, heart, and eventually death of patients. Fibrosis is initiated by a variety of pathological, physiological, biochemical, and physical factors. Regardless of their different etiologies, they all share a common pathogenetic process: excessive activation of the key profibrotic cytokine, transforming growth factor-β (TGF-β). Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor of the nuclear receptor superfamily, has received particular attention in recent years, because the activation of PPARγ by both natural and synthetic agonists could effectively inhibit TGF-β-induced profibrotic effects in many organs. DATA SOURCES: The English-language medical databases, PubMed, Elsevier and SpringerLink were searched for articles on PPARγ, TGF-β, and fibrosis, and related topics. RESULTS: TGF-β is recognized as a key profibrotic cytokine. Excessive activation of TGF-β increases synthesis of extracellular matrix proteins and decreases their degradation, associated with a gradual destruction of normal tissue architecture and function, whereas PPARγ agonists inhibit TGF-β signal transduction and are effective antifibrogenic agents in many organs including the liver, lung, kidney, skin and heart. CONCLUSIONS: The main antifibrotic activity of PPARγ agonists is to suppress the TGF-β signaling pathway by so-called PPARγ-dependent effect. In addition, PPARγ agonists, especially 15d-PGJ2, also exert potentially antifibrotic activity independent of PPARγ activation. TGF-β1/Smads signaling not only plays many essential roles in multiple developmental processes, butalso forms cross-talk networks with other signal pathways, and their inhibition by PPARγ agonists certainly affects the cytokine networks and causes non-suspected side-effects. Anti-TGF-β therapies with PPARγ agonists may have to be car

关键词： PPAR gamma transforming growth factor-β fibrosis

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Hepatobiliary & Pancreatic Diseases International 2011年第4期10卷 356-361页

作者： Pei-Xian Chen and Lu-Nan Yan Division of Liver Transplantation,west china hospital,sichuan university,chengdu 610041,china Division of Liver Transplantation West China Hospital Sichuan University Chengdu 610041 China

BACKGROUND:Living donor liver transplantation (LDLT) has recently emerged as an effective therapeutic alternative for patients with end-stage liver *** the meantime,the health-related quality of life (HRQoL) of the donors is becoming better *** we aimed to review the current literature and summarize the effects of liver donation on the long-term HRQoL of living *** SOURCES:A literature search of PubMed using 'donors','living donor liver transplantation','health-related quality of life',and 'donation' was performed,and all the information was ***:The varied postoperative outcomes of liver donors are attributive to the different evaluation instruments *** the whole,donors experienced good long-term physical and mental well-being with a few complaining of compromised quality of life due to mild symptoms or psychiatric *** psychosocial dimension has received increasing attention with the vocational,interpersonal and financial impact of liver donation on donors mostly ***:Generally,donors have a good HRQoL after ***,to achieve an ideal donor outcome,further work is necessary to minimize the negative effects as well as to incorporate recent progress in regenerative medicine.

关键词： living donor liver transplantation donation health-related quality of life

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Interventional treatments for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2006年第4期5卷 495-500页

作者： Yong-Song Guan and Yuan Liu department of Radiology, west china hospital, sichuan university, chengdu 610041, china department of Radiology West China Hospital Sichuan University Chengdu 610041 China. YongsongGuan@***

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However, only 20% of HCCs can be surgically treated. And most of surgically-noneligible patients have to receive interventional managements including local ablation and transarterial chemoembolization (TACE). In this paper, we review the interventional treatments of HCC. DATA SOURCES: A literature search of PubMed database was conducted and research articles were reviewed. RESULTS: Percutaneous ethanol injection (PEI) is usually applied to small HCC for a complete necrosis. Radiofrequency ablation, an alternative to PEI, also causes tumor necrosis and needs fewer times of ablation. Other methods such as acetic acid injection, laser, microwave, etc have enriched local ablation for HCC. High intensity focus ultrasound (HIFU) is thought to be promising. TACE, another common modality, can improve the survival rate of patients with HCC. The newly developed embolic agents and adjuvant rAd-p53 gene therapy are well reported. CONCLUSIONS: Surgically-noneligible HCC can be treated with interventional procedures. Each method has its advantages and disadvantages. However, it is still pressing to develop ablative methods as well as new embolic agents for a better prognosis of HCC.

关键词： carcinoma, hepatocellular local ablative therapy transarterial chemoembolization

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The Synthesis of an Optically Active Intermediate of A-Ring for 1α,25-Dihydroxy Vitamin D_3 Analogs

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Chinese Chemical Letters 1998年第5期9卷 431-432页

作者： Yong WU and (School of Pharmacy, west china university of Medical Sciences, chengdu 610041)Mei GUAN (The First hospital, west china university of Medical Sciences, chengdu 610041) W china Univ Med Sci Sch Pharm Chengdu 610041 Peoples R China W china Univ Med Sci Hosp 1 Chengdu 610041 Peoples R China

Synthesis of an optically active intermediate 4b for the A-ring of 1a,25-dihydroxyvitamin D3 analogs has been achieved in eight steps, starting from readily available, inexpensive D-(+)-xylose.

关键词： 1α 25-dihydroxyvitamin D_3 D(+)-xylose synthesis

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