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Internalization and distribution of three α1-adrenoceptor subtypes in HEK293A cells before and after agonist stimulation

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Acta Pharmacologica Sinica 2007年第3期28卷 359-366页

作者： Shu-yi WANG~2 Yao SONG~2 Ming XU~2 Qi-hua HE~3 Qi-de HAN~2 You-yi ZHANG~(2,4)2 Institute of Vascular Medicine,peking university Third Hospital and Key Laboratory of Molecular Cardiovascular sciences,Ministry of Education,beijing 100083.china 2 center of medical analysis,peking university,health science center,beijing 100083.china Institute of Vascular Medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing China center of medical analysis Peking University Health Science Center Beijing China

Aim:To examine the subcellular distribution of the 3 α1-adrenoceptor（α1-AR）subtypes and their internalization and trafficking upon agonist stimulation in hu-man embryonic kidney 293A ***:Confocal real-time imaging,enzymelinked immunosorbent assay（ELISA）and whole cell[3H]-prazosin binding assaywere applied to detect the distribution and localization of the 3 α1B-AR ***:α1A-AR was found both on the cell surface and in the cytoplasm;α1B-AR,however,was predominantly detected on the cell surface,while α1D-AR wasdetected mainly in the intracellular *** stimulation withphenylephrine,localization changes were detected by confocal microscopy forα1A-and α1B-AR, but the localization of α1D-AR were *** promoted a more rapid internalization of α1B-AR than α1A-AR.α1D-ARinternalization was detected only by *** cell[3H]-prazosin bindingassay showed that α1A-AR functional receptors were detected both on the cellsurface and in the cytoplasm;α1B-AR,however,were detected predominantly onthe cell surface,while α1D-AR were detected mainly in intracellular *** stimulation promoted internalization of α1A-and α***:Phenylephrine stimulation induced changes in the localization of the3α1-AR.

关键词： adrenoceptor agonist stimulation confocal image enzyme-linked immunosorbent assay [~3H]-prazosin binding assay internalization subcellular distribution subtype

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Effects of Ganoderma lucidum polysaccharides on proliferation and cytotoxicity of cytokine-induced killer cells

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Acta Pharmacologica Sinica 2005年第9期26卷 1130-1137页

作者： Xiao-ling ZHU Zhi-bin LIN Department of Pharmacology,School of Basic medical science,peking university health science center,beijing 100083.china Department of Pharmacology School of Basic Medical Science Peking University Health Science Center Beijing 100083 China

Aim:To study the effects(and the mechanisms thereof)of Ganoderma lucidumpolysaccharides(G/-PS)on the proliferation and the anti-tumor activity of cytokine-induced killer(CIK)cells,and to make use of CIK cells as a means to investigatethe interactions between Gl-PS and ***:CIK cells were preparedby using the standard protocol as a positive *** groups alsounderwent the standard protocol,except that Gl-PS(400 mg/L or 100 mg/L)wasadded and the dose of anti-CD3 and interleukin-2 they received was reduced by50% and 75%,*** negative controls,Gl-PS in the experimentalprotocol was replaced with soluble starch or methylcellulose(400 mg/L or 100 mg/L).CIK cell proliferation,cytotoxicity,and phenotype were determined by using theTrypan blue exclusion method,MTT assay,and flow ***:Bysynergizing cytokines,Gl-PS(400 mg/L or 100 mg/L)could decrease the amountof cytokine in lymphokine activated killer(LAK)cells and CIK cells culture,buthad no significant effect on the proliferation,cytotoxicity,or phenotype of LAKcells,or CIK cells induced by cytokines at higher doses alone,in which CIK cellsexpanded about 80-fold and the main effectors,CD3~+NK1.1~+ cells,expanded bymore than 15%.The cytotoxicity of CIK cells in experimental groups was 79.3%±4.7%,76.9%±6.8% versus the positive control 80.7%±6.8% against P815(P>0.05)and 88,9%±5.5%,84.7%±7.9% versus the positive control 89.8%±4.5% againstYAC-1(P>0.05).The activity of GI-PS could mostly be blocked by ***:GI-PS was shown to be a promising biological response modifier andimmune *** effect of GI-PS on CIK cells is possibly mediated prima-rily through complement receptor type 3.

关键词： Ganoderma lucidum polysaccharides cell proliferation cytotoxicity immunomodula-tion

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2023 Guideline for the management of hypertension in the elderly population in china

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Journal of Geriatric Cardiology 2024年第6期21卷 589-630页

作者： Hypertension Branch of Chinese Geriatrics Society,beijing Hypertension Association,National Clinical Research center of the Geriatric Diseases Qi HUA Li FAN Zeng-Wu WANG Jing LI 不详 Xuanwu Hospital Capital Medical UniversityBeijingChina Chinese PLA General Hospital BeijingChina Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Preamble Hypertension is one of the most common chronic diseases and the primary risk factor for stroke,myocardial infarction and even cardiovascular *** than half of the elderly population has high blood *** people are a unique group,and strategies for the prevention,diagnosis,evaluation,and treatment of hypertension in elderly individuals differ significantly from those in the general population.

关键词： hypertension prevention diagnosis

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Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide

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Acta Pharmacologica Sinica 2004年第6期25卷 131-136页

作者： Qi-zhen CAO, Zhi-bin LIN1 Department of Pharmacology, health science center, peking university, beijing 100083, china Department of Pharmacology Health Science Center Peking University 100083

AIM: To investigate the antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide (GLPP). METHODS: Antitumor effect of GLPP was observed in tumor-bearing mice in vivo. At the same time, the effects of GLPP on proliferation of tumor cells and human umbilical cord vascular endothelial cell (HUVEC) were detected by MTTassay in vitro. Subsequently, spleen lymphocytes proliferation of nude mice was stimulated by LPS or ConA. To investigate the anti-angiogenic effect of GLPP, GLPP 80 μg per disc and GLPP-treated serum 10 μL per disc were added to the chick chorioallantoic membrane (CAM) respectively in vivo. RESULTS: GLPP 50, 100, and 200 mg/kg inhibited growth of Sarcoma 180 in BALB/c mice markedly by 35.2 %, 45.2 %, and 61.9 %, respectively. GLPP which was directly added to the cultured medium did not inhibit PG cell proliferation in vitro; but GLPP-treated serum 50, 100, 200 mg/kg potently inhibited PG cell proliferation by 22.5 %, 26.8 %, and 30.3 %, respectively; and reduced the xenograft (human lung carcinoma cell PG) in BALB/c nude mice greatly in vivo by 55.5 %, 46.0 %, and 46.8 %, respectively. Lymphocytes proliferation of nude mice could be stimulated by LPS 5 mg/Lbut not by ConA 2.5 mg/L, indicating that GLPP could not promote the T lymphocyte proliferation and neutral red phagocytosis of peritoneal macrophages of nude mice. The CAM assay showed that GLPP and GLPP-treated serum had anti-angiogenic effect. GLPP (1, 10, and 100 mg/L) inhibited HUVEC proliferation in vitro with the inhibitory rate of 9.4 %, 15.6 %, and 40.4 %, respectively. CONCLUSION: GLPP has antitumor and anti- angiogenic activity. The anti-angiogenesis of GLPP may be a new mechanism underlying its anti-tumor effects.

关键词： Ganoderma lucidum polysaccharides sarcoma 180 adenocarcinoma lung neoplasms lympho- cyte proliferation peritoneal macrophages angiogenesis nude mice

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中国政治经济学年度发展报告（2023）（下）

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政治经济学评论 2024年第3期 90+207-208页

作者： center for Studies of Contemporary Political Economy,Research Institute for 21st-Century Marxism,Nankai university·university of Chinese Academy of Social science center for Teaching and Research on Capital,Renmin university of china National Institute of Socialist Political Economy with Chinese Characteristics,Renmin university of china 南开大学·中国社会科学院大学21世纪马克思主义研究院当代政治经济学研究中心中国人民大学《资本论》教学与研究中心中国人民大学全国中国特色社会主义政治经济学研究中心

编者按2023年，高质量发展扎实推进，新质生产力加快形成，我国经济总体回升向好，圆满实现发展主要预期目标。为针对性地破解经济恢复发展中的难题，聚焦推进中国式现代化进程中的重点、难点问题，中国政治经济学界开展系统深入研究，...

编者按2023年，高质量发展扎实推进，新质生产力加快形成，我国经济总体回升向好，圆满实现发展主要预期目标。为针对性地破解经济恢复发展中的难题，聚焦推进中国式现代化进程中的重点、难点问题，中国政治经济学界开展系统深入研究，取得系列代表性成果。为准确刻画学界研究进展和轨迹，推动中国经济学理论体系的构建和完善，本刊精选议题如期奉上《中国政治经济学年度发展报告（2023）》。自2010年起，本刊连续十四年发布《中国政治经济学年度发展报告》，“年度发展报告”专栏已成为本刊标志性特色栏目。2023年报告聚焦12个专题，分为（上）（下）两篇，其中专题1—6于报告（上）篇刊登，专题7—12由报告（下）篇刊登。2023年报告（下）选题如下：

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Chinese expert consensus on refined diagnosis,treatment,and management of advanced primary liver cancer(2023 edition)

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肝脏研究（英文） 2024年第2期8卷 61-71页

作者： Xiufeng Liu Feng Xia Yue Chen Huichuan Sun Zhengqiang Yang Bo Chen Ming Zhao Xinyu Bi Tao Peng Aizier Ainiwaer Zhiwen Luo Fusheng Wang Yinying Lu National Clinical Research center for Infectious Diseases Society of Hepatology,beijing medical Association Translational Medicine Branch,china Association of Gerontology and Geriatrics Department of medical Oncology Bayi Hospital Affiliated to Nanjing Chinese Medical University NanjingJiangsuChina Department of Hepatobiliary Surgery Southwest HospitalArmy Medical University ChongqingChina Senior Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Interventional Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Minimally Invasive Interventional Therapy Liver Cancer Study and Service GroupSun Yat-sen University Cancer CenterGuangzhouGuangdongChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxiChina Senior Department of Infectious Diseases The Fifth Medical Center of PLA General HospitalBeijingChina Comprehensive Liver Cancer center The Fifth Medical Center of PLA General HospitalBeijingChina

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in china,accounting for approximately 85％of all cancer cases in the *** guidelines have been used to diagnose and treat liver ***,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual ***,it is necessary to establish a comprehensive and practical expert consensus,specifically for china,to enhance the diagnosis and treatment of HCC using the Delphi *** classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were *** recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment *** findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

关键词： Hepatocellular carcinoma (HCC) Targeted therapy Immunotherapy Refined diagnosis and treatment Expert consensus

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Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptorinduced cardiomyocyte hypertrophy

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Acta Pharmacologica Sinica 2006年第7期27卷 895-900页

作者： Da-li LUO~(2,3,5) Jian GAO~2 Xiao-mei LAN~3 Gang WANG~4 Sheng WEI~4 Rui-ping XIAO~4 Qi-de HAN~32 Department of Pharmacology,School of Chemical Biology & Pharmaceutical sciences,Capital university of medical sciences,beijing 100069,china 3 Institute of Cardiovascular science at health science center,peking university beijing 100083.china 4 Institute of Molecular Medicine and College of Life science,peking university,beijing 100871,china Department of Pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing China Institute of Cardiovascular science at health science center Peking University Beijing China Institute of Molecular Medicine and College of Life science Peking University Beijing China

Aim:Intracellular Ca2+plays pivotal roles in diverse cellular functions,includinggene transcription that underlies cardiac remodeling during stress ***,the role of inositol 1,4,5-trisphosphate receptors（IP3Rs）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3Rsmay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3Rs was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3BM）,a membrane-permeant ester of IP3,to activate IP3Rs directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3BM(10μmol·L-1)mimicked theeffects of phenylephrine,a selective agonist of α1AR,in increments in local Ca2+spark release（especially in the perinuclear area）and global Ca2+*** importantly,IP3R inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3BM-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3H]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3R signaling to α1AR-stimulatedgene expression and cardiomyocyte hypertrophy.

关键词： inositol 1,4,5-trisphosphate receptors Ca2+sparks α1 adrenergic stimulation cardiac hypertrophy

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Real-time detection of α1A-AR movement stimulated by phenylephrine in single living cells

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Acta Pharmacologica Sinica 2007年第6期28卷 796-802页

作者： Ning XU~(2,5),Zhang-yi LIANG~(3,5),Ming XU~2,Ying-hua GUAN~3,Qi-hua HE~4,Qi-de HAN~2,Xin-sheng ZHAO~(3,6),You-yi ZHANG~(2,6)~2 Institute of Vascular Medicine,peking university Third Hospital,and Key Laboratory of Molecular Cardiovascular sciences,Ministry ofEducation,beijing 100083.china ~3 beijing National Laboratory for Molecular sciences,State Key Laboratory for Structural Chemistry ofUnstable and Stable Species,and Department of Chemical Biology,College of Chemistry and Molecular Engineering,peking university,beijing 100871,china ~4 center of medical analysis,peking university,health science center,beijing 100083.china Institute of Vascular Medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing China beijing National Laboratory for Molecular sciences State Key Laboratory for Structural Chemistry of Unstable and Stable Species Department of Chemical Biology College of Chemistry and Molecular Engineering Peking University Beijing China center of medical analysis Peking University Health Science Center Beijing China

Aim:To investigate the movement of α1A-adrenergic receptors(α1A-AR) stimu-lated by agonist,phenylephrine （PE）,and the dynamics of receptor movement inreal time in single living cells with millisecond ***:We labeledα1A-AR using the monoclonal,anti-FLAG （a kind of tag） antibody and Cy3-conju-gated goat anti-mouse IgG and recorded the trajectory of their transport processin living HEK293A cells stimulated by agonist,PE,and then analyzed their dy-namic ***:The specific detection of α1A-AR on the surface ofliving HEK293A-α1Acells was achieved.α1A-AR internalize under the stimulationof *** the cells were stimulated with PE for 20 min,apparent colocalizationwas found between α1A-AR and *** 40 min stimulation of PE,trajecto-ries of approximate linear motion in HEK293A-α1Acells were recorded,and theirvelocity was ***:The specific labeling method on the livingcell surface provides a convenient means of real-time detection of the behavior ofsurface *** this method we were able to specifically detect α1A-AR andrecord the behavior of individual particles of receptors with 50 ms exposure time inreal time in single living cells.

关键词： adrenergic receptor trajectory living cell

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Kinetics of thymocyte developmental process in fetal and neonatal mice

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Cell Research 2003年第4期13卷 265-273页

作者： SHI YUN XIAO, YAN LI, WEI FENG CHENDepartment of Immunology, School of Basic medical sciences, peking university health science center, 38 Xueyuan Road, beijing 100083, china Department of Immunology School of Basic Medical Sciences Peking University Health Science Center Beijing China

Kinetics of thymocyte development in vivo during embryogenesis was pursued. The early development of thymocytes in the fetal and neonatal BALB/c mice was discontinuous, with four waves of cell proliferation occurring at fetal day (Fd) 14 to 17, Fd 18 to day (D) 1 after birth, D 2 to D 5 and D6 thereafter. The first three proliferation waves coincided with the generation of CD4/"CD8/" (DP), TCR+CD4/hiCD8-/lo (CD4 SP), and TCR+CD4-/loCD8int/hi (CD8 SP) thymocytes, respectively. The transition from DN to DP cells was further investigated and it was found out that there were two differential pathways via immature single positive (ISP) cells in the BALB/c mice, each functioning at different fetal ages. One is via TCR-CD4-CD8+ cells, occurring between Fd 15 and Fd 17 and the other is via TCR-CD4+CD8- cells, occurring from Fd 17 until birth. In contrast, the TCR-CD4-CD8+ pathway dominated overwhelmingly in the C57BL/6 mice. These findings shed new light on the hypothesis that the differential pathway preferenc

关键词： fetal thymus neonatal mice thymocyte ontogeny.

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p38 MAPK mediates cardiovascular and behavioral responses induced by central IL-1β and footshock in conscious rats

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Acta Pharmacologica Sinica 2004年第3期25卷 12-16页

作者： Rui-mao ZHENG,Chang-jiang ZOU,Shi-gong ZHU2 Department of Physiology and Pathophysiology,health science center,peking university,beijing 100083.china Department of Physiology and Pathophysiology Health Science Center Peking University 北京 100083

AIM: To investigate the roles of p38 mitogen-activated protein kinase (p38 MAPK) in the cardiovascular and behavioral responses induced by intracerebral ventricular injection (icv) of interleukin-1β (IL-1β) or footshock. METHODS: We examined the effects of p38 MAPK on mean artery blood pressure (mABP), heart rate (HR), and motor activity (MA) during central administration of IL-1β, or footshock after icv SB203580 (a specific inhibitor of the p38 MAPK) with Cardiovascular and Behavior Telemetry System in conscious SD rats. RESULTS: (1) IL-1β (icv) or footshock remarkably rise the mABP, and the maximal changes are (7.8±1.8) and (12.3±3.5) mmHg, respectively, which was abrogated by the pretreatment with p38 inhibitor SB203580 intracerebroventricularly. (2) Compared with icv saline group, the motor activity was significantly decreased in SB203580 group with maximal changes (-7.6±1.1) counts/min after footshock. CONCLUSION: p38 MAPK plays an important role in the pres- sor response induced by central administration of IL-1β or footshock and change of motor activity after footshock in conscious rats.

关键词： mitogen-activated protein kinase p38 interleukin-1 blood pressure motor activity

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