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ERG3 potassium channel-mediated suppression of neuronal intrinsic excitability and prevention of seizure generation in mice

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中国药理学与毒理学杂志 2018年第9期32卷 713-714页

作者： XIAO Kuo SUN Zhi-ming jin xue-qin MA Wei-ning SONG Yan LAI Shi-rong FAN Ming-hua ZHANG jing-liang YUE Wei-hua HUANG Zhuo State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China Department of Neurology Shengjing Hospital affiliated to China Medical UniversityShenyang 110000China Peking University Sixth Hospita(Institute of Mental Health) Beijing 100191China National clinical Research Center for Mental Disorders&Key Laboratory of Mental Health Ministry of Health(Peking University)Beijing 100191China Key Laboratory for Neuroscience Ministry of EducationBeijing 100191 china

The input-output relationship of neuronal networks depends heavily on the intrinsic properties of their neuronal *** changes in intrinsic properties have been observed in various physiological and pathological processes,such as learning,memory and ***,the cellular and molecular mechanisms underlying acquired changes in intrinsic excitability are still not fully ***,we demonstrate that ERG3 channels are critically involved in the regulation of intrinsic excitability in hippocampal CA1 pyramidal neurons and DG granule ***-down of ERG3 channels significantly increases neuronal intrinsic excitability,which is mainly caused by decreased fast afterhyperpolarization,delayed time to the generation of an action potential and enhanced summation of somatic excitatory post-synaptic ***,the expression level of ERG3 protein is significantly reduced in human and mouse brain tissues with temporal lobe ***,ERG3 channel knock-down in hippocampus significantly enhanced seizure susceptibility,while mice treated with ERG3 channel activator NS1643 were less prone to *** together,our results suggest ERG3 channels play an important role in determining the excitability of hippocampal neurons and dysregulation of these channels may be involved in the generation of ***3 channels may thus be a novel therapeutic target for the prevention of epilepsy.

关键词： ERG3 channels intrinsic property dysregulation epilepsy

A randomized comparative study of using enoxaparin instead of unfractionated heparin in the intervention treatment of coronary heart disease

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Chinese Medical Journal 2006年第5期119卷 355-359页

作者： CHEN Ji-lin CHEN Jue QIAO Shu-bin GUO Yuan-lin WU Yong-jian DAI Jun YUAN jin-qing qin xue-wen YANG Yue-jin GAO Run-lin Cardiovascular Institute and Fuwai Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing 100037 China

Background Low molecular weight heparin （LMWH） was more effective than unfractionated heparin （UFH） in treating acute coronary syndrome （ACS）. However, it remains uncertain whether LMWH can be used in patients undergoing percutaneous coronary intervention （PCI） instead of UFH. This study aimed to evaluate the efficacy and safety of using enoxaparin instead of UFH in the intervention treatment of patients with coronary heart disease （CHD） .Methods From October 2003 to Febuary 2005, 966 patients with CHD were enrolled into this study. Among 966 patients, 455 patients received the PCI, including 283 patients with Non-ST segment elevation ACS （NSTEACS）, 511 patients did not received PCI due to mild, moderate lesions or were suitable for coronary artery bypass graft （CABG）. The 966 patients were randomized to enoxaparin group （484 patients） and UFH group （482 patients）. Patients in the enoxaparin group were given enoxaparin at least twice subcutaneously （1 ms/kg, q12 h） before catheterization. Plasma anti-Xa activity was determined 1-8 hours after the last dose of enoxaparin was determined. The catheterization was performed within 8 hours after the last dose of enoxaparin. The sheath was removed immediately after the procedure. Patients in the UFH group were given UFH 25 mg intravenously before coronary angiography. Additional 65 mg was given intravenously if PCI was to be performed. The sheath was removed 4 hours after the procedure. Results A total of 227 patients in the enoxaparin group and 228 patients in the UFH group received PCI. In the enoxaparin group, one patient developed acute thrombosis during PCI and resulted in acute myocardial infarction （AMI）, no acute or subacute thrombosis was found during hospitalization. In the UFH group, no acute or subacute thrombosis occurred during PCI procedure and hospitalization. Therefore, the incidence of major adverse cardiovascular events （MACEs） during the hospitalization was 0.44% in the enoxaparin group and 0 in the

关键词： enoxaparin unfractionated heparin percutaneous coronary intervention

Coronary intervention in patients ≥75 years old with ST-elevation myocardial infarction： in-hospital and 6-month clinical outcomes

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Chinese Medical Journal 2010年第16期123卷 2171-2175页

作者： ZHENG Xin LI Jian-jun YUAN jin-qing qin xue-wen ZHU Cheng-gang GUO Yuan-lin MU Chao-wei HUA Yi-hong YANG Yue-jin XU Bo GAO Run-lin Department of Cardiology Fu Wai Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100037 China

Background ST-segment elevation myocardial infarction （STEMI） in elderly patients presents specific clinical *** study on percutaneous coronary intervention （PCI） in elderly patients （≥75 years） with STEMI,however, has less been *** In the present study, 522 consecutive STEMI patients undergoing PCI within 12 hours from symptom onset were investigated, and clinical characteristics and in-hospital and 6-month outcomes of 66 elderly patients （≥75 years,group A） were compared to those of 456 younger patients （〈75 years, group B）.Results Compared to younger patients, elderly ones had more females （42.4% vs.17.8%, P 〈0.005）, a history of cerebral vascular events （7.6% vs.0.9%, P 〈0.05）, higher serum creatinine level （（96.48±31.65） mmol/L vs.（84.87±19.81）mmol/L, P〈0.005） and fewer smokers （28.8% vs.45.4%, P〈0.05）.The elderly ones had worse Killip class （Killip I class：69.7% vs.85.7%, P 〈0.05）, less drug-eluting stent implantation and lower rates of TIMI flow 3 following PCI （33.3% vs.47.1%, and 84.8% vs.94.7%, P 〈0.05 respectively）.Additionally, both in-hospital mortality and myocardial infarction rate were found to be higher in elderly patients （16.7% vs.1.5%, and 7.6% vs.2.6%, P 〈0.05 respectively）, which were also observed until 6-month follow-up （9.1% vs.0, and 6.1% vs.0, P 〈0.05 respectively=.In multivariable Cox regression analysis, serum creatinine level, history of hypertension, left anterior descending coronary artery as infarct-related artery and Killip class were independent predictors of 6-month overall death in elderly *** The clinical characteristics of elderly patients with STEMI after PCI are different from those of younger *** PCI in this population is with a low rate of PCI failure, it is still associated with a worse outcome.

关键词： percutaneous coronary intervention elderly myocardial infarction

Gender difference of clinical characteristics in Chinese patients with spontaneous variant angina

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Chinese Medical Journal 2010年第11期123卷 1377-1381页

作者： ZHU Cheng-gang LI Jian-jun XU Yan-lu YUAN jin-qing qin xue-wen YANG Yue-jin QIAO Shu-bin CHEN Ji-lin CHEN Zai-jia GUO Yuan-lin GAO Zhan ZHENG Xin Department of Cardiology Fu Wai Hospital Peking UnionMedical College and Chinese Academy of Medical SciencesBeijing 100037 China

Background Spontaneous attack of variant angina （VA） is a unique component of coronary artery disease （CAD）, and associated with severe cardiac events. However, no data are available regarding sex differences in Chinese patients with spontaneous attacks of VA. Accordingly, the present retrospective study was initiated to evaluate the Clinical characteristics of Chinese female patients with spontaneous attacks of VA. Methods From January 2003 to January 2008, a total of 209 patients were diagnosed to have had a spontaneous attack of VA at Fu Wai Hospital. Of them, 27 were female, and their clinical findings were collected and compared with male patients for aspects of risk factors, clinical features and angiographical findings. Results Spontaneous attacks of VA was relatively uncommon in female （12.9%） compared with male patients. The female patients were less likely to have a history of smoking （14.8% vs. 79.7%, P 〈0.001）, more likely to have a family history of CAD （33.3% vs. 11.0%, P 〈0.01）, and to have had a greater incidence of ventricular fibrillation during attack （11.1% vs. 2.2%, P 〈0.05）. There were no significant differences in other characteristics between the two groups. Conclusion Chinese female patients who experienced a spontaneous attack of VA had the characteristics of less smokina history, more family history of CAD and higher occurrence of ventricular fibrillation than male patients.

关键词： coronary spasm coronary artery disease gender

Dopamine D2 Receptors Regulate the Action Potential Threshold by Modulating T-type Calcium Channels in Stellate Cells of the Medial Entorhinal Cortex

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神经药理学报 2019年第Z1期 22-23页

作者： jin xue-qin CHEN Qian SONG Yan ZHENG Jie XIAO Kuo SHAO Shan FU Zi-bing YI Ming YANG Yang 黄卓 State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science Center Neuroscience Research Institute Key Laboratory for Neuroscience Ministry of Education/National Health and Family Planning CommissionPeking University Department of Medicinal Chemistry and Molecular Pharmacology College of PharmacyPurdue University Purdue Institute for Integrative Neuroscience 北京药理学会

Stellate cells in the medial entorhinal cortex（MEC） are considered to constitute the largest population of grid cells,which provide spatial representation to support animal estimation of location. Although dopaminergic fibers from the ventral tegmental area and substantia nigra pars compacta innervate the majority of the cortex,including the MEC,little is known about how dopamine modulates the function of MEC stellate cells. Because dopamine D2 receptors（D2 Rs） are involved in spatial cognition and the MEC contains high levels of D2 Rs,we investigated how D2 R activation modulates the neuronal intrinsic excitability of stellate cells. Electrophysiological recordings,optogenetics and molecular biology experiments were performed on mice to investigate the mechanism. Activation of axonal D2 Rs via endogenous dopamine release or selective D2 R agonist elevated the action potential threshold and decreased the intrinsic excitability of layer Ⅱ stellate cells,which was caused by modulation of the activation properties of T-type Ca;channels in a D2 R-PKA–dependent manner. In support,immunofluorescent assays revealed colocalization of D2 Rs and Ca;3.2 calcium channels within the axon initial segment. These findings are likely to have significant implications on understanding the cellular processes by which dopamine influences neuronal excitability and it may also be applicable to other hippocampal and cortical regions as dopaminergic fibers innervate wide brain regions. Taken together,these findings provide insights into the mechanism of D2 Rs modulating action potential（AP） threshold of stellate cells through T-type Ca;channels in MEC.

关键词： Dopamine D2 Receptors Regulate the Action Potential Threshold by Modulating T-type Calcium Channels in Stellate Cells of the Medial Entorhinal Cortex Action Cortex

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P91钢的热压缩动态组织演化数值模拟

锻压技术 2012年第3期37卷 119-122,126页

作者：金雪芹张建毕大森天津理工大学材料科学与工程学院天津300384

针对电站大口径厚壁无缝管典型用钢T/P91(10Cr9Mo1VNb),利用Gleeble-3500热模拟试验机采集了T/P91耐热钢的高温流动应力-应变曲线。以Avrami方程为基础,结合单项热压缩实验发生完全动态再结晶试样的金相分析,回归得到方程中的模型参数,... 详细信息

针对电站大口径厚壁无缝管典型用钢T/P91(10Cr9Mo1VNb),利用Gleeble-3500热模拟试验机采集了T/P91耐热钢的高温流动应力-应变曲线。以Avrami方程为基础,结合单项热压缩实验发生完全动态再结晶试样的金相分析,回归得到方程中的模型参数,从而确立P91合金钢在不同变形条件下的动态再结晶数学模型。采用De-form数值模拟软件对热模拟实验动态再结晶过程进行数值模拟,对比金相实验结果,验证P91合金钢动态再结晶数学模型的正确性。

关键词： P91耐热钢数值模拟流变应力动态再结晶

高雅外态与低俗心理的鲜明对比——简析《永远的尹雪艳》

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青海师专学报 2002年第2期22卷 78-80页

作者：金学琴湖州师范学院初等教育系浙江湖州313000

作者着意写女主人公内心丑 ,却反而极写其外态美。独特新颖的构思、新鲜题材的择用和以形写神的含蓄的表现手法是作品成功的保证。

关键词：白先勇小说构思题材艺术手法美丑文学赏析《永远的尹雪艳》

大口径厚壁管道热挤压成形过程微观组织模拟及实验研究

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塑性工程学报 2019年第3期26卷 169-178页

作者：李攀罗建国卜祥丽金雪芹占克勤杨绍兰华北科技学院机电工程学院河北廊坊065201 约翰迪尔(天津)有限公司天津300450 湖北三环锻造有限公司湖北襄阳441000

针对某型核能发电用P91大口径厚壁无缝管道进行了不同挤压比条件下的垂直正挤压成形过程缩比数值模拟,研究了管道微观组织在挤压过程中的演变规律。研究表明:挤压过程中金属温度场变化和局部变形速率对管道晶粒组织演变具有重要影响。... 详细信息

针对某型核能发电用P91大口径厚壁无缝管道进行了不同挤压比条件下的垂直正挤压成形过程缩比数值模拟,研究了管道微观组织在挤压过程中的演变规律。研究表明:挤压过程中金属温度场变化和局部变形速率对管道晶粒组织演变具有重要影响。相同工艺因素条件下,平均晶粒尺寸在轴向上从变形区到挤出端逐渐递增,而在径向上从管道内侧到外侧逐渐递减;管道内侧的动态再结晶百分数高于外侧;管道金属在轴向比径向有更高的动态再结晶发生率,且动态再结晶晶粒尺寸比径向更小。管道的平均晶粒尺寸随着挤压比的增加呈减小的趋势,挤压比越大,动态再结晶发生的越充分,越利于晶粒细化。进行了与数值模拟相配套的缩比挤压成形实验,并针对获得的样件分别进行了金相实验和晶粒度评定,所测得的平均晶粒尺寸变化规律与数值模拟基本吻合,证明了数值模拟的正确性,同时验证了增大挤压比对管道晶粒细化具有重要的促进作用。

关键词：大口径厚壁管道热挤压数值模拟微观组织演变实验验证

Increased plasma C-reactive protein level predicts rapid progression of non-target atherosclerotic lesions in patients with stable angina after stenting

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Chinese Medical Journal 2011年第19期124卷 3022-3029页

作者： XU Yan-lu LI Jian-jun XU Bo ZHU Cheng-gang YANG Yue-jin CHEN Ji-lin QIAO Shu-bing YUAN jin-qing qin xue-wen MA Wei-hua YAO Min LIU Hai-bo WU Yong-jian CHEN Jue YOU Shi-jie DAI Jun XIA Ran GAO Run-lin Department of Cardiology Fu Wai Hospital Chinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100037 China

Background Although the role of C-reactive protein （CRP） in predicting rapid progression of atherosclerotic lesions has been intensively studied in unstable coronary artery disease, the data from patients with stable angina （SA） are largely absent. The present study evaluated a middle-size patient cohort who underwent percutaneous coronary intervention （PCI） with stent implantation and follow-up coronary angiography （CAG） and tested the hypothesis that increased plasma level of high-sensitive CRP would indicate rapid progression of de novo non-target coronary artery lesions in Chinese patients with *** The study population comprised of 311 consecutive patients with chronic SA who underwent coronary stent implantation on initial admission and angiographic follow-up （（8.5±1.2） months）. Rapid angiographic progression of non-target lesion was angiographically assessed and the patients were classified into two groups according to whether the progression existed or not. The relation of plasma CRP levels to the progression of atherosclerosis was *** Baseline demographic, clinical, and angiographic data were similar in patients with and without *** angiographic progression of non-target lesions occurred in 136 patients （43.7%） at follow-up： 77 had a ≥10%diameter reduction of pre-existing stenosis ≥50%, 26 had a ≥30% diameter reduction of a pre-existing stenosis 〈50%, 64 developed a new lesion ≥30% in a previously normal segment, and 4 had progression of a lesion to total *** of non-target lesions was not associated with target lesion restenosis formation. High-sensitive CRP levels were markedly higher in progression patients than in non-progression ones （1.60 （0.80-3.46） mg/L vs. 0.96 （0.55-1.87）mg/L, P 〈0.001）. Multivariate regression analysis showed that plasma CRP independently predicted rapid angiographic progression of non-target lesions （P=0.001）. High-sensitive CRP levels above 1.32 mg/L （the cutoff value） were

关键词： C-reactive protein inflammation angina pectoris angiography stents