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CHARISMA试验:阿司匹林与氯吡格雷联合阿司匹林预防动脉粥样硬化事件的对照研究

中国现代神经疾病杂志 2009年第1期9卷 102-102页

作者： Bhatt DL fox ka Hacke W 王蔚不详南京医科大学第一附属医院神经内科 210029

CHARISMA（Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events）试验旨在比较阿司匹林单药治疗与阿司匹林和氯吡格雷联合治疗预防动脉粥样硬化事件的疗效。有26个国家参与了该项研究，共纳... 详细信息

CHARISMA（Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events）试验旨在比较阿司匹林单药治疗与阿司匹林和氯吡格雷联合治疗预防动脉粥样硬化事件的疗效。有26个国家参与了该项研究，共纳入15603例≥45岁受试者，均符合下列条件：具有动脉粥样硬化多种危险因素，或具有明确的冠心病、脑血管疾病及症状性外周动脉疾病。

关键词：动脉粥样硬化阿司匹林氯吡格雷预防试验 Prevention Aspirin 外周动脉疾病

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Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver

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Cellular & Molecular Immunology 2022年第7期19卷 834-847页

作者： Wenshu Tang Jingying Zhou Weiqin Yang Yu Feng Haoran Wu Myth T.S.Mok Lingyun Zhang Zhixian Liang Xiaoyu Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li Hanyong Sun Xiaoyu Tian Philip Chun Yeung Yong Hou Heung Man Lee Candice C.H.Lam Howard H.W.Leung Anthony W.H.Chan ka Fai To John Wong Paul B.S.Lai Kelvin K.C.Ng Simon K.H.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.Y.Sung Alfred S.L.Cheng school of Biomedical Sciences The Chinese University of Hong KongHong Kong SAR 999077China Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SAR 999077China Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Surgery The Chinese University of Hong KongHong Kong SAR 999077China Department of Medicine and Therapeutics The Chinese University of Hong Kong.Hong Kong SAR 999077China State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SAR 999077China Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 639798Singapore Institute of Precision Medicine The First Affliated HospitalSun Yat-sen UniversityGuangzhou 510080China

Obesity is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty liver disease(NAFLD).Hypercholesterolemia is a common comorbidity of *** cholesterol biosynthesis mainly occurs in the liver,its role in HCC development of obese people remains *** high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor *** analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD ***,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC ***,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not CD8^(+)T cell ***,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and *** study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.

关键词： Cancer microenvironment Cancer models Tumour immunology

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陕西汉中洋县金水河口旧石器遗址出土石制品研究（英文）

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人类学学报 2019年第3期38卷 344-361页

作者：别婧婧王社江夏楠鹿化煜王先彦弋双文夏文婷张改课 Mathew L.fox 张红艳卓海昕张文超中国科学院古脊椎动物与古人类研究所中国科学院脊椎动物演化与人类起源重点实验室北京100044 中国科学院大学北京100049 中国科学院生物演化与环境卓越创新中心北京100044 陕西省考古研究院西安710054 南京大学地理与海洋科学学院南京210023 亚利桑那大学人类学系图森85710

位于汉水左岸一级支流金水河第四级阶地的金水河口遗址是汉水流域发现较早的一处旧石器遗址。2014年6月~2015年2月,为了配合国家重点建设工程——南水北调西线“引汉济渭”项目的实施,我们对金水流域金水镇附近的3个旧石器遗址进行了正... 详细信息

位于汉水左岸一级支流金水河第四级阶地的金水河口遗址是汉水流域发现较早的一处旧石器遗址。2014年6月~2015年2月,为了配合国家重点建设工程——南水北调西线“引汉济渭”项目的实施,我们对金水流域金水镇附近的3个旧石器遗址进行了正式发掘,金水河口遗址即为其中之一。该遗址发掘面积370m^2,出土不同类型石制品1210件。研究显示在金水河口遗址生活的古人类主要选取附近河滩砾石为原料进行剥片及工具加工。石制品的岩性以石英和石英岩为主,硅质灰岩次之,并少量使用了石英砂岩和花岗岩原料。古人类主要使用锤击法剥片。遗址中石核的利用效率较低,近半数石片有直接使用的痕迹。加工工具的毛坯以石片为主。工具类型除了刮削器、凹缺器、石锥等小型工具之外,还有砍砸器、手镐、重型刮削器等重型工具。遗址中碎屑数量很少。石制品组合以刮削器等小型工具为主,也包含少量重型工具。相较于汉中盆地已发现的遗址,金水河口遗址的文化面貌与洛南盆地中更新世的龙牙洞遗址更相似,但是重型工具的比例更高。由于遗址堆积物已超出了钾长石红外后释光测年法(post-IRIRSL)的测年范畴,目前只能给出遗址的埋藏时间下限,即埋藏石制品地层的年代不晚于150ka。作为汉中盆地有明确测年的中更新世晚期遗址,金水河口遗址为我们系统了解汉江支流金水河流域和秦岭地区的石器工业特点、遗址地层堆积及年代等提供了新的、丰富的材料。

关键词：汉中盆地金水河金水河口遗址石制品第四级阶地中更新世晚期

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive *** an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)*** of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,***,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic ***,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer T cell

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