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| 1 | Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system显示文摘允许的技术内长的基因的特定的规定为基因功能的学习是珍贵的并且在治疗学有大潜力。我们创造了在 CRISPR 上系统,由核酸酶死者 Cas9 (dCas9 ) 蛋白质组成的二部件的 transcriptional 使活跃之物与互补顺序与 transcriptional 激活域和单个指南 RNA (sgRNAs ) 熔化了到基因倡导者。我们证明在 CRISPR 上能高效地以一种悦耳的方式在人和老鼠房间激活外长的记者基因。另外,我们证明在 vivo 的柔韧的记者基因激活能被把系统部件注入老鼠接合子完成。而且,我们证明在 CRISPR 上能激活内长的 IL1RN, SOX2,和 OCT4 基因。最有效的基因激活被对近似倡导者有约束力的 3-4 sgRNAs 的簇完成,建议他们在基因正式就职的 synergistic 行动。显著地,当指向多重基因的 sgRNAs 同时被介绍进房间时,柔韧的多路的内长的基因激活被完成。染色体宽的表示介绍表明了系统的高特性。 | Albert W Cheng Haoyi Wang Hui Yang Linyu Shi Yarden Katz Thorold W Theunissen Sudharshan Rangarajan Chikdu S Shivalila Daniel B Dadon Rudolf Jaenisch | 2013 | Cell Research2013，23，10： | 65 |
| 2 | Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma显示文摘BACKGROUND:Hepatocellular carcinoma (HCC) is characterized by a multi-cause,multi-stage and multi-focus process of tumor progression.Its prognosis is poor and early diagnosis is of utmost importance.This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC.METHODS:A hepatoma model was induced in male Sprague-Dawley rats with 0.05% 2-fluorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) expression.Total RNA was purified and transcribed into cDNA by reverse transcription.Fragments of the GPC-3 gene were amplified by nested RT-PCR,and confirmed by sequencing.GPC-3 was analyzed by immunohistochemistry,Western blotting or ELISA.RESULTS:Positive GPC-3 expression showed as brown granule-like staining localized in the cytoplasm.Histological examination of hepatocytes revealed three morphological stages of granule-like degeneration,atypical hyperplasia (precancerous),and cancer formation,with a progressive increase of liver total RNA and GGT expression.The incidence of liver GPC-3 mRNA and GPC-3,and serum GPC-3 was 100%,100% and 77.8% in the HCC group,100%,100%,and 66.7% in the precancerous group,83.3%,83.3%,and 38.9% in the degeneration group,and no expression in the liver or blood of the control group,respectively.There was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475,P<0.05) or liver GPC-3 (r=1.0,P<0.001) or serum GPC-3 (r= 0.994,P<0.001).CONCLUSION:Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC. | Research Center of Clinical Medicine,Affiliated Hospital of Nantong University,Nantong 226001,China (Yao M,Yao DF,Qiu LW,Wu W,Sai WL,Yang JL and Zhang HJ) Department of Oncology,Yancheng First People’s Hospital,Yancheng 224001,China (Bian YZ) Department of Oncology,Second Affiliated Hospital,Nanjing Medical University,Nanjing 210011,China (Zhang CG) | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，3： | 51 |
| 3 | A randomized controlled clinical trial on the treatment of Thymosin-a1 versus interferon-α in patients with hepatitis B显示文摘INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organization estimates that HBV has infected mord than 350 million people worldwide ,and up to 20% of them will become chromic carricrs and will be at significant risk for cirrhosis and HCC .The ultimate goal of the therapy for chronic hepatitis B is to prevent progression to cirrhosis and to prevent development of HCC. | Jing You Lin Zhuang Bao Zhang Tang Wei Bo Yang Su Ying Ding Wu Li Rong Xue Wu Hong Li Zhang Yan Mei Zhang Shao Ming Yan Lu Zhang ~1Department of Infectious Diseases,The First Affiliated Hospital of Kunming Medical College,Kunming 650032,Yunnan Province,China ~2Departrnent of Hepatology,Kunming Third Municipal People’s Hospital,Kunming 650041,Yunnan Province,China | 2001 | World Journal of Gastroenterology2001，7，3： | 48 |
| 4 | Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients显示文摘AIM: To investigate the effect of omega-3 fatty acid parenteral supplementation postoperatively on clinical outcomes and immunomodulation in colorectal cancer patients. METHODS: Forty-two patients undergoing radical colorectal cancer resection with an indication for total parenteral nutrition postoperatively were enrolled in this prospective, double-blind, randomized, controlled study. Patients received total parenteral nutrition supplemented with either soybean oil (LCT; Intralipid, Fresenius-Kabi, SO group, n = 21) or a combination of omega-3 fish oil and soybean oil (LCT:fish oil = 5:1, fish oil; Omegaven, Fresenius-Kabi, FO group, n = 21), up to a total of 1.2 g lipid/kg per day for 7 d postoperatively. A same volume calorie and nitrogen was administrated. Routine blood test, biochemistry, systemic levels of IL-6 and TNF-α, percentage of CD3+, CD4+, and CD8+ lymphocytes were evaluated preoperatively and on postoperative d 1 and 8. Patient outcome was evaluated considering mortality during the hospital stay, length of postoperative hospital stay, and occurrence of infectious complications. RESULTS: Both lipid regimens were well tolerated. No differences between the two groups were noticed in demographics, baseline blood test, biochemistry, serum levels of IL-6 and TNF-α, percentage of CD4+, CD8+ lymphocytes, and ratios of CD4+/CD8+. Compared with those on postoperative d 1, serum IL-6 levels onpostoperative d 8 were significantly depressed in the FO group than in the reference group (-44.43 ± 30.53 vs -8.39 ± 69.08, P = 0.039). Simultaneously, the ratios of CD4+/CD8+ were significantly increased in the FO group (0.92 ± 0.62 vs 0.25 ± 1.22, P = 0.035). In addition, depression of serum TNF-α levels (-0.82 ± 2.71 vs 0.27 ± 1.67, P = 0.125) and elevation of CD3+ and CD4+ lymphocyte percentage (12.85 ± 11.61 vs 3.84 ± 19.62, P = 0.081, 17.80 ± 10.86 vs 9.66 ± 17.55, P = 0.084, respectively) were higher in the FO group than in the reference group. Patients in the FO group trended to need a shorter postoperative hospital stay (17.45 ± 4.80 d vs 19.62 ± 5.59 d, P = 0.19). No statistically significant difference was found when stratified to mortality and occurrence of infectious complications. CONCLUSION: Postoperative supplementation of omega-3 fatty acids may have a favorable effect on the outcomes in colorectal cancer patients undergoing radical resection by lowering the magnitude of inflammatory responses and modulating the immune response. | Bin Liang, Shan Wang, Ying-Jiang Ye, Xiao-Dong Yang, You-Li Wang, Jun Qu, Qi-Wei Xie, Mu-Jun Yin, Division of Surgical Oncology and Division of Gastroenterological Surgery, Peking University People’s Hospital, Beijing 100044, China Author contributions: Liang B and Wang S contributed equally to this work Liang B and Wang S designed the research Liang B, Ye YJ, Yang XD, Wang YL, Qu J, Xie QW, Yin MJ performed the research and collected the data Wang S and Ye YJ supervised the research Liang B and Ye YJ analyzed the data Liang B wrote the paper and revised the manuscript. | 2008 | World Journal of Gastroenterology2008，14，15： | 31 |
| 5 | 番茄采摘机器人机械臂避障路径规划显示文摘以关节型机械臂避开垂直茎秆或撑杆采摘番茄为研究对象,提出了一种基于构形空间的关节型机械臂避障路径规划方法。利用空间映射原理,将关节型机械臂工作空间的三维避障问题转换为平面R-R机械臂避开障碍圆的问题,用临界碰撞关节角建立C-障碍空间的映射计算模型,将工作空间的位置避障转换为构形空间连杆关节角的计算。以能量最优函数优选避障规划的关节终点角度,利用A*算法计算平面R-R机械臂的避障关节角路径,获得一系列表示空间连杆位置的相交竖直面,并在竖直面内进行其余关节角的规划。避障采摘番茄的试验表明,机械臂带动夹持器能成功绕过直线状障碍物,引导夹持器到达果实目标位置,证明对平面R-R机械臂的空间映射建模是正确的,验证了提出的避障路径规划方法是可行的,可以应用于番茄的自动收获。 | 尹建军 武传宇 Yang Simon X Gauri S Mittal 毛罕平 | 2012 | 农业机械学报2012，43，12： | 33 |
| 6 | Clinicopathological features of gastric glomus tumor显示文摘AIM:To study the clinicopathological features of gastric glomus tumor and review the related Chinese literature published in 1990-2010.METHODS:A case of gastric glomus tumor was re-ported.Clinicopathological findings in 56 cases of gastric glomus tumor were analyzed.RESULTS:Gastric glomus tumor was far more common in women than in men with a female to male ratio of 1.6:1.The median age of the patients was 45 years(range 28-79 years).The patients often complained of epigastric pain and bloody stool.The tumor was located in antrum of the stomach.The greatest diameter of the tumor was 0.8-11cm.Histologically,the tumor was comprised of nests of glomus cells surrounding the capillaries.Glomus cells were small,uniform and round.Vimentin,smooth muscle actin and actin were expressed in the tumor.Other markers,including S-100 protein,CD34,CD117,desmin,CD56,synaptophysin,chromo-granin A,neuron specific enolase and cytokeratin were all negative.CONCLUSION:Gastric glomus tumor is a rare benign mesenchymal neoplasm.Its diagnosis depends on pathologic examination.Differential diagnosis includes gastrointestinal stromal tumor,paraganglioma and carcinoid tumor. | Hui-Qiong Fang,Jing Yang,Fen-Fen Zhang,An-Jia Han,Department of Pathology,First Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510080,Guangdong Province,China Hui-Qiong Fang,Department of Pathology,Foshan Hospital of Traditional Chinese Medicine,Foshan 528000,Guangdong Province,China Jing Yang,Department of Pathology,People’s Hospital of Zhu-hai City,Zhuhai 519000,Guangdong Province,China Yi Cui,Department of Gastroenterology,First Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510080,Guangdong Province,China | 2010 | World Journal of Gastroenterology2010，16，36： | 28 |
| 7 | Structure and function of aggrecan显示文摘Aggrecan is the major proteoglycan in the articular cartilage. This molecule is important in the proper functioning of articular cartilage because it provides a hydrated gel structure (via its interaction with hyaluronan and link protein) that endows the cartilage with load-bearing properties. It is also crucial in chondroskeletal morphogenesis during development. Aggrecan is a multimodular molecule expressed by chondrocytes. Its core protein is composed of three globular domains (G1, G2, and G3) and a large extended region (CS) between G2 and G3 for glycosaminoglycan chain attachment. G1 comprises the amino terminus of the core protein. This domain has the same structural motif as link protein. Functionally, the G1 domain interacts with hyaluronan acid and link protein, forming stable ternary complexes in the extracellular matrix. G2 is homologous to the tandem repeats of G1 and of link protein and is involved in product processing. G3 makes up the carboxyl terminus of the core protein. It enhances glycosaminoglycan modification and product secretion. Aggrecan plays an important role in mediating chondrocyte-chondrocyte and chondrocyte-matrix interactions through its ability to bind hyaluronan. | CHRIS KIANI, LIWEN CHEN, YAO JIONG WU, ALBERT J YEE, BURTON B YANG, Sunnybrook and Women’s College Health Sciences Centre and Department of Laboratory Medicine and Patobiology, 2 Department of Surgeny, Faculty of Medicine, University of Toronto, Canada | 2002 | Cell Research2002，12，1： | 27 |
| 8 | 茶黄素双没食子酸酯的抗癌活性及其作用机理研究显示文摘以SephadexLH-20柱色谱分离得到茶黄素双没食子酸酯(TFDG)成分,以H1299和HCT-116细胞分析了该成分的抗癌活性及其作用机理。结果表明,TFDG具有良好的抑制H1299细胞生长的活性,IC50为25μmol/L;有调节细胞周期的活性,可增加HCT-116细胞G1期细胞的比例;有促进HCT-116细胞凋亡的作用,浓度为50μmol/L时效果显著,48h凋亡率达到40%以上;Western杂交技术分析结果表明,它可降低HCT-116细胞中促癌蛋白质因子Bcl-xL的表达量,可增加抑癌蛋白质因子Bax的表达量。 | 江和源 Hang Xiao 袁新跃 王川丕 Chung S Yang | 2007 | 茶叶科学2007，27，1： | 25 |
| 9 | Vasculogenic mimicry is a prognostic factor for postoperative survival in patients with glioblastoma显示文摘A previous report has confirmed the existence and clinical significance of vasculogenic mimicry(VM)in glioma.However,its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and,thus,might be unconvincing.The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma.Patients were classified as VM-positive or | Wang SY Ke YQ Lu GH Song ZH Yu L Xiao S Sun XL Jiang XD Yang ZL Hu CC | 2013 | 中国神经肿瘤杂志2013，11，3： | 22 |
| 10 | Changed clinical aspects of primary liver cancer in China during the past 30 years显示文摘BACKGROUND: Primary liver cancer (PLC) is one of the most frequently seen tumors in China. Thirty years ago, patients with PLC were often detected at relatively late stage, with a palpable mass or marked clinical symptoms and poor prognosis. In the past 30 years, the diagnosis and treatment of PLC have been greatly improved with better prognosis. METHODS: In order to study the changes of PLC during the 30 years, the clinical data of 3250 patients with PLC from 10 medical institutions of China were collected, ana- lyzed , and compared with those of 3254 PLC patients be- fore the 30 years. RESULTS: In the 3250 patients aged 1-80 years, with an average age of 49.1 years, the male to female ratio (2.3:1) was lower than that before the 30 years. 73.5% of the 3250 patients sought medical advice within 3 months after the onset of the disease in contrast to 63.8% before the 30 years. Compared with those patients before the 30 years the symptoms and signs were alleviated generally. The HBsAg positive rate was 81.0%, but the HCV-Ab positive rate was 13.2%. The AFP level in 75% of patients was elevated, but in the remaining 25% was normal. 1912 patients (58.8%) were confirmed pathologically. Among them 1755 patients (91.8%) had hepatocellular carcinoma. The overall resec- tion rate was 46.3%. Those who had early, middle, late stage carcinoma accounted for 29.9%, 51.5%, and 18.6%respectively in contrast to 0.4%, 47.0%, and 52.6% repor- ted before the 30 years. The 1-, 3-, 5-year survival rates of the patients were 66.1%, 39.7%, and 32.5% respectively, whereas 93.5%, 70.1%, and 59.1% for the early stage pa- tients, and 65.3%, 30.5%, and 23.5% for the middle stage patients. The half and 1-year survival rates of the late stage patients were 52.5%, and 14.7%, respectively. CONCLUSION: Comparison with the clinical data before and after the 30 years show that PLC can be diagnosed ear- ly. More PLC patients tend to undergo resection while re- ceiving a better conservative treatment, which ensures a prognosis. | Bing-Hui Yang, Jing-Lin Xia, Li-Wen Huang, Zhao-You Tang, Ming-Shan Chen, Jin-Qing Li, An-Min Liang, Qin-Guo Mo, Hui-Shan Lu, Chao-Liu Dai, Lu-Nan Yan, Zhi-Jian Yu, Rong-Sheng Rao, Le-Qun Li, Zhi-Xiong Su, Zhuang-Wei Fang Shanghai, China Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai 200032, China Tumor Hospital, Zhongshan University, Guangzhou 510000, China Tumor Hospital, Guangxi Medical Universi- ty, Nanning 530000, China Xiehe Hospital, Fujian Medical University, Fuzhou 350000, China Second Hos- pital, Chinese Medical University, Shenyang 110000, China Huaxi Hospital, Sichuan University, Chengdu 610041, China Hospital Affiliated to Nantong Medical University, Nantong 226000 , China Second Hospital, Jiangxi Medical University, Nanchang 330000 , China First Hospital Affiliated to Guangxi Medical University, Nanning 530000 , China People’s Hospital of Hainan Province, Haikou 570000, China | 2004 | Hepatobiliary & Pancreatic Diseases International2004，3，2： | 20 |
| 11 | Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment显示文摘AIM: To investigate the long-term survival and prognostic factors in hepatocellular carcinoma(HCC) patients undergoing radiofrequency ablation(RFA) as a first-line treatment.METHODS: From 2000 to 2013, 316 consecutivepatients with 404 HCC(1.0-5.0 cm; mean: 3.2 ± 1.1 cm) underwent ultrasonography-guided percutaneous RFA as a first-line treatment. There were 250 males and 66 females with an average age of 60.1 ± 10.8 years(24-87 years). Patients were followed for 1 year to > 10 years after RFA(234, 181, 136, and 71 for 3, 5, 7, and 10 years, respectively). Overall local response rates and long-term survival rates were assessed. Survival results were generated using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression model. RESULTS: In total, 548 RFA sessions were performed and major complications occurred in 10 sessions(1.8%). Local tumor progression and/or new tumor development were observed in 43.3%(132/305) of the patients during the follow-up period. Overall 5-and 10-year survival rates were 49.7% and 28.4%, respectively. Based on multivariate analysis, three factors were identified as independent prognostic factors for overall survival: Child-Pugh classification(HR = 4.054, P < 0.001), portal vein hypertension(HR = 2.743, P = 0.002), and tumor number(HR = 2.693, P = 0.003). The local progression-free 5- and 10-year survival rates were 42.7% and 19.5%. In addition to the Child-Pugh classification and the number of tumors, the number of RFA sessions(HR = 1.550, P = 0.002) was associated with local progression-free survival.CONCLUSION: RFA can achieve acceptable outcomes for HCC patients as a first-line treatment, especially for patients with Child-Pugh class A, patients with a single tumor and patients without portal vein hypertension. | Wei Yang Kun Yan S Nahum Goldberg Muneeb Ahmed Jung-Chieh Lee Wei Wu Zhong-Yi Zhang Song Wang Min-Hua Chen | 2016 | World Journal of Gastroenterology2016，22，10： | 20 |
| 12 | Effect of PA-MSHA vaccine on plasma phospholipids metabolic profiling and the ratio of Th2/Thl cells within immune organ of mouse IgA nephropathy显示文摘 | Jia, LW Wang, C Kong, HW Yang, J Li, FL Lv, S Xu, GW | 2007 | 中国生物学文摘2007，21，11： | 19 |
| 13 | Extraction and purification of TGFβ and its effect on the induction of apoptosis of hepatocytes显示文摘AIM To extract and purify the transforming growth factor β (TGF β), and to demonstrate its biological activity in vivo and induction of apoptosis of hepatocytes in vitro.METHODS TGF β was isolated from fresh bovine platelets by acid/ethanol extraction method and purified with ion exchange and gel chromatography. The extracted TGF β was injected subcutaneously to mice, and its biological activity in vivo was observed 72 hfs post-injection by HE staining. The morphological changes were observed by HE staining and the occurrence of apoptosis was detected by TUNEL method after the human normal hepatic cell line QZG was treated with 8 μg@L 1 TGFβ for 12 hrs in vitro.RESULTS The molecular mass 25 ku TGF β protein was successfully extracted. It was able to induce localized granulation tissue formation in vivo. TGF β-treated hepatocytes showed obvious apoptotic morphological changes, including the pyknosis and dense-stained nuclei and cytoplasm, the fragmentary, annular or crescent nuclei, and the 'bubbling' cytoplasm. Moreover, its apoptotic rate was significantly higher than that of the control group (P<0.05).CONCLUSION Biological active TGF β protein is extracted and purified successfully from bovine platelets, and it is able to induce the apoptosis of hepatocytes. | Xiao-Hui Si Lian-Jun Yang Research Institute of Stomatology,the Ninth People’s Hospital,Shanghai Second Medical University,Shanghai 200011,ChinaDepartment of Pathology,Fourth Military Medical University,Xi’an 710033,Shaanxi Province,China | 2001 | World Journal of Gastroenterology2001，7，4： | 15 |
| 14 | Mineral inclusions of zircon and UHP metamorphic evidence from paragneiss and orthogneiss of pre-pilot drill-hole CCSD-PP2 in north Jiangsu Province,China显示文摘Coesite inclusions, together with omphacite, jadeite, garnet and phengite inclusions, were identified in zircons separates from almost all gneissic core samples of pre-pilot drillhole CCSD-PP2 by the Laser Raman spectros-copy and the cathodoluminescence method. These data indicate that gneissic rocks consisting of paragneisses and or-thogneisses ubiquitously experienced UHP metamorphism. This research may be of great significance for an in-depth study of the subduction-exhumation mechanism of the Sulu UHP metamorphic belt and selecting the drilling site for the Chinese Continental Scientific Drilling Project. | LIU Fulai XU Zhiqin YANG Jingsui S Maruyama J.G.Liou I.Katayama H.Masago | 2001 | Chinese Science Bulletin2001，46，12： | 12 |
| 15 | Ecological Economic Problems and Development Patterns of the Arid Inland River Basin in Northwest China显示文摘中国西北部干旱区的内陆河流域位于欧亚大陆的中心(35°N,106°E),占全国陆地总面积的24.5%,是世界上最干旱的地区之一。该区具有较为湿润的山地和干旱的平原地带性交替特征。发源于山区的几条河流,如黑河、石羊河.疏勒河和塔里木河,在流经中游地区,孕育了一些生机盎然的绿洲后,注入一些小的湖泊或者消失在广袤的干旱荒漠盆地。山地.绿洲和沙漠相间分布的景观特征是中国西北干旱区内陆河流域典型的景观格局。尽管该区相对于其他的干旱地区来说有较多的农牧业生产活动,水资源问题仍然是限制该区经济发展的重要影响因素。我们以黑河流域作为一个案例, | Lihua Zhou Key Laboratory of Desert and Desertification,Cold and Arid Regions Environmental and Engineering Research Institute,Chinese Academy of Sciences,320 Dong Gang West Road,Lanzhou 730000,People’s Republic of China lhzhou@lzb.ac.cnGuojing Yang Laboratory of Watershed Hydrology and Ecology,Cold and Arid Regions Environmental and Engineering Research Institute,Chinese Academy of Sciences,320 Dong Gang West Road,Lanzhou 730000,People’s Republic of China ygj7518@163.com | 2006 | AMBIO-人类环境杂志2006，35，6： | 11 |
| 16 | The enhanced X-ray Timing and Polarimetry mission—eXTP显示文摘In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources.The paper provides a detailed description of:(1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload;(2) the elements and functions of the mission, from the spacecraft to the ground segment. | ShuangNan Zhang Andrea Santangelo Marco Feroci YuPeng Xu FangJun Lu Yong Chen Hua Feng Shu Zhang Sφren Brandt Margarita Hernanz Luca Baldini Enrico Bozzo Riccardo Campana Alessandra De Rosa YongWei Dong Yuri Evangelista Vladimir Karas Norbert Meidinger Aline Meuris Kirpal Nandra Teng Pan Giovanni Pareschi Piotr Orleanski QiuShi Huang Stephane Schanne Giorgia Sironi Daniele Spiga Jiri Svoboda Gianpiero Tagliaferri Christoph Tenzer Andrea Vacchi Silvia Zane Dave Walton ZhanShan Wang Berend Winter Xin Wu Jean J.M.in't Zand Mahdi Ahangarianabhari Giovanni Ambrosi Filippo Ambrosino Marco Barbera Stefano Basso Jörg Bayer Ronaldo Bellazzini Pierluigi Bellutti Bruna Bertucci Giuseppe Bertuccio Giacomo Borghi XueLei Cao Franck Cadoux Francesco Ceraudo TianXiang Chen Yu Peng Chen Jerome Chevenez Marta Civitani Wei Cui WeiWei Cui Thomas Dauser Ettore Del Monte Sergio Di Cosimo Sebastian Diebold Victor Doroshenko Michal Dovciak YuanYuan Du Lorenzo Ducci QingMei Fan Yannick Favre Fabio Fuschino JoséLuis Ga'lvez Min Gao MingYu Ge Olivier Gevin Marco Grassi QuanYing Gu YuDong Gu DaWei Han Bin Hong Wei Hu Long Ji ShuMei Jia WeiChun Jiang Thomas Kennedy Ingo Kreykenbohm Irfan Kuvvetli Claudio Labanti Luca Latronico Gang Li MaoShun Li Xian Li Wei Li ZhengWei Li Olivier Limousin HongWei Liu XiaoJing Liu Bo Lu Tao Luo Daniele Macera Piero Malcovati Adrian Martindale Malgorzata Michalska Bin Meng Massimo Minuti Alfredo Morbidini Fabio Muleri Stephane Paltani Emanuele Perinati Antonino Picciotto Claudio Piemonte JinLu Qu Alexandre Rachevski Irina Rashevskaya Jerome Rodriguez Thomas Schanz ZhengXiang Shen LiZhi Sheng JiangBo Song LiMing Song Carmelo Sgro Liang Sun Ying Tan Phil Uttley Bo Wang DianLong Wang GuoFeng Wang Juan Wang LangPing Wang YuSa Wang Anna L.Watts XiangYang Wen Jörn Wilms ShaoLin Xiong JiaWei Yang Sheng Yang YanJi Yang Nian Yu WenDa Zhang Gianluigi Zampa Nicola Zampa Andrzej A.Zdziarski AiMei Zhang ChengMo Zhang Fan Zhang Long Zhang Tong Zhang Yi Zhang XiaoLi Zhang ZiLiang Zhang BaoSheng Zhao ShiJie Zheng Yu Peng Zhou Nicola Zorzi J.Frans Zwart | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，2： | 11 |
| 17 | Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor a and carnitine palmitoyl acyl-CoA transferase 1A显示文摘AIM: To elucidate the role of the peroxisome proliferator-activated receptor α (PPARα) and its target gene carnitine palmitoyl acyl-CoA transferase 1A (CPT1A)in the pathogenesis of hepatitis C virus (HCV) infection.METHODS: Liver samples were collected from the patients with chronic HCV infection and controls. HepG2cells were transfected with vector pEF352neo carrying.Two independent clones (clone N3 and N4) stably expressing HCV core protein were analyzed. Total RNA was extracted from cells and liver tissues. PPARα and CPT1A mRNAs were quantified by real-time polymerase chain reaction (PCR) using SYBR Green Master. Total extracted proteins were separated by polyacrylamide gel electrophoresis, and electroblotted. Membranes were incubated with the anti-PPARα antibody, then with a swine anti-rabbit IgG conjugated to horseradish peroxidase for PPARα. Protein bands were revealed by an enhanced chemiluminescence reaction for PPARα. For immunohistochemical staining of PPARα, sections were incubated with the primary goat polyclonal antibody directed against PPARα at room temperature.RESULTS: Real-time PCR indicated that the PPARα level and expression level of CPT1A gene in hepatitis C patients lowered significantly as compared with the controls (1.8±2.8 vs 13±3.4, P = 0.0002; 1.1±1.5 vs 7.4+1, ,P = 0.004). Western blot results showed that the level of PPARα protein in the livers of hepatitis C patients was lower than that in controls (2.3±0.3 vs 3.6±0.2,P = 0.009). The immunohistochemical staining results in chronic hepatitis C patients indicated a decrease in PPARα staining in hepatocytes compared with those in the control livers. The in vitro studies found that in the N3 and N4 colon stably expressing HCV core protein, the PPARα mRNA levels were significantly lower than that in the controls.CONCLUSION: The impaired intrahepatic PPARα expression is associated with the pathogenic mechanism in hepatic injury during chronic HCV infection. HCV infection reduced the expression of PPARα and CPT1A at the level of not only mRNAs but also proteins. PPARα plays an important role in the pathogenesis of chronic HCV infection, but the impaired function of this nuclear receptor in HCV infection needs further studies. | Yang Cheng Sébastien Dharancy Mathilde Malapel Pierre Desreumaux | 2005 | World Journal of Gastroenterology2005，11，48： | 11 |
| 18 | Metformin does not improve survival in patients with hepatocellular carcinoma显示文摘AIM:To assess whether metformin,which has a chemopreventive effect in chronic liver disease,has any chemotherapeutic effect in hepatocellular carcinoma.METHODS:This was a retrospective study of 701 patients with newly diagnosed hepatocellular carcinoma(HCC)seen between January 2005 and June 2011 at Mayo Clinic,Rochester,Minnesota.This patient cohort was a part of the global HCC BRIDGE study,which is a large longitudinal study of HCC determining the realworld experience of HCC characteristics,management and patient outcomes.We defined significant metformin exposure as continuation of this agent at least 90d beyond diagnosis of HCC,and compared survival of diabetic patients on metformin to diabetic patients not on metformin and non-diabetics.RESULTS:Our cohort was 72.9%male,with a mean±SD age of 62.6±12.3 years.The most common etiologies of liver disease were hepatitis C(34%),alcoholic liver disease(29%),fatty liver disease(15%)and hepatitis B(9%).By univariate analysis,using diabetics not on metformin as the reference group,diabetic patients with HCC on metformin had no survival advantage,with a HR(95%CI)of 1.0(0.8-1.3).Non-diabetic HCC patients also did not appear to have a survival advantage as compared to diabetic HCC patients not on metformin,as demonstrated by a HR(95%CI)of1.1(0.7-1.7).Diabetics on metformin beyond 90 d after HCC diagnosis had a longer median survival at 34.2 mo,as compared to 25.5 mo among diabetic patients who were not on metformin or had discontinued metformin within 90 d after HCC diagnosis.This finding was likely due to potential survival bias among those who lived long enough to receive metformin.CONCLUSION:Although the literature suggests a chemotherapeutic effect in other malignancies,our study demonstrates no survival benefit to the use of metformin in diabetic patients with HCC. | Mamatha Bhat Roongruedee Chaiteerakij William S Harmsen Cathy D Schleck Ju Dong Yang Nasra H Giama Terry M Therneau Gregory J Gores Lewis R Roberts | 2014 | World Journal of Gastroenterology2014，20，42： | 11 |
| 19 | Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell lines显示文摘This study aimed to investigate the effects of arsenic trioxide(As2O3) on the mitochondrial DNA(mtDNA) of acute promyelocytic leukemia(APL) cells.The NB4 cell line was treated with 2.0 μmol/L As2O3 in vitro,and the primary APL cells were treated with 2.0 μmol/L As2O3 in vitro and 0.16 mg kg-1 d-1 As2O3 in vivo.The mitochondrial DNA of all the cells above was amplified by PCR,directly sequenced and analyzed by Sequence Navigatore and Factura software.The apoptosis rates were assayed by flow cytometry.Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use,but the mutation spots were remarkably increased after As2O3 treatment,which was positively correlated to the rates of cellular apoptosis,the correlation coefficient:rNB4-As2O3=0.973818,and rAPL-As2O3=0.934703.The mutation types include transition,transversion,codon insertion or deletion,and the mutation spots in all samples were not constant and regular.It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo.Mitochondrial DNA might be one of the targets of As2O3 in APL treatment. | MENG Ran1,ZHOU Jin2,SUI Meng3,LI ZhiYong4,FENG GuoSheng1 & YANG BaoFeng2 1 Division of Neurology,the Ninth Clinical Medical College of Beijing University(Shijitan Hospital),Beijing 100038,China 2 The First Hospital of Harbin Medical University,Harbin 150001,China 3 Management Information System,University of International Business and Economics,Beijing 100029,China 4 Department of Radiology,Cambridge University Hospitals NHS Foundation Trust Box 219 Level 5,Addenbrooke’s Hospital Cambridge CB2 0QQ,UK | 2010 | Science China(Life Sciences)2010，53，1： | 10 |
| 20 | Current status of intravenous tissue plasminogen activator dosage for acute ischaemic stroke:an updated systematic review显示文摘The optimal dose of recombinant tissue plasminogen activator(rtPA)for acute ischaemic stroke(AIS)remains controversial,especially in Asian countries.We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA.We performed a systematic literature search across MEDLINE,Embase,Cochrane Central Register of Controlled Trials(CENTRAL),PsycINFO and Cumulative Index to Nursing and Allied Health Literature(CINAHL)from inception to 22 August 2016 to identify all related studies.The outcomes were death or disability(defined by modified Rankin Scale 2-6),death,and symptomatic intracerebral haemorrhage(sICH).Where possible,data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis.We included 26 observational studies and 1 randomised controlled trial with a total of 23210 patients.Variable doses of rtPA were used for thrombolysis of AIS in Asia.Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability(OR 1.13,95% CI 0.95 to 1.33),or death(OR 0.86,95% CI 0.74 to 1.01),or decreased risk of sICH(OR 1.06,95% CI 0.65 to 1.72).The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies.Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS.Low-dose rtPA was not associated with lower risk of death or disability,death alone,or sICH. | Xia Wang Shoujiang You Shoichiro Sato Jie Yang Cheryl Carcel Danni Zheng Sohei Yoshimura Craig S Anderson Else Charlotte Sandset Thompson Robinson John Chalmers Vijay K Sharma | 2018 | Stroke & Vascular Neurology2018，3，1： | 10 |
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