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Hydroxyl radicals induced by quartz particles in lung alveolar macrophages: the role of surface iron

Progress in Natural science:Materials International 2006年第10期16卷 1038-1044页

作者： LI Yi, ZHU Tong, GUO Xinbiao and SHANG Yu ( State Key Joint Laboratory for Environmental Simulation & Pollution Control, peking university, beijing 100871, {3. Occupational & Environmental health sciences, School of Public health, peking university health science center, beijing {13., {3.) [a]State Key Joint Laboratory for Environmental Simulation & Pollution Control Peking University Beijing China [b]Occupational & Environmental health sciences School of Public Health Peking University Health Science Center Beijing China

Previous studies have shown that hydroxyl radical generation is a key step in the mechanism of pathogenic process caused by airborne particles to the lung. However, there is no direct evidence for dose-response relationship between airborne particles and hydroxyl radical generation. In this study, hydroxyl radicals generated in lung alveolar macrophages exposed to quartz particles were measured using a highly sensitive capillary electrophoresis-fluorescence detection method. The results demonstrated that quartz particles induced the generation of hydroxyl radical in a dose-dependent manner, and the amount of the hydroxyl radicals was 10-10 mol/10 cells. The viability of alveolar macrophages exposed to quartz particles decreased with the increase of quartz concentration, showing a clear dose-response relationship. Hydroxyl radical scavenger mannitol could increase the viability of quartz-treated cells, suggesting that hydroxyl radical contributed directly to cell death. In this study this contribution accounted for about 5%-20% of cell death. The hydroxyl radical generating potential was found to be related to surface iron content of the quartz particles.

关键词： inhalable quartz hydroxyl radical capillary electrophoresis dose-response relationship iron.

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补体相关性肾病诊断和治疗专家共识

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中华内科杂志 2024年第3期63卷 258-271页

作者：北京大学医学部肾脏病学系专家组赵明辉不详北京大学第一医院肾内科、北京大学肾脏病研究所北京100034

随着补体系统在各类肾脏疾病中的作用机制逐渐阐明,针对补体活化不同环节的药物相继出现,部分已应用于临床。但补体靶向治疗仍存在诸多问题。北京大学医学系补体相关性肾病诊断和治疗专家共识协作组在国内外肾脏疾病指南/共识的基础上,... 详细信息

随着补体系统在各类肾脏疾病中的作用机制逐渐阐明,针对补体活化不同环节的药物相继出现,部分已应用于临床。但补体靶向治疗仍存在诸多问题。北京大学医学系补体相关性肾病诊断和治疗专家共识协作组在国内外肾脏疾病指南/共识的基础上,结合最新证据制定了本共识,简述了补体相关性肾病的发病机制、诊断思路、补体靶向治疗与特殊致病微生物的疫苗免疫等方面的最新证据和建议,为补体相关性肾病的诊断和治疗提供参考。

关键词：补体相关性肾病诊断治疗补体抑制剂

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Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs

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Acta Pharmacologica Sinica 2004年第12期25卷 93-99页

作者： Ya-li ZHANG, Xiao-hong TAN2, Mei-fang XIAO, Hui LI, Yi-qing Mao, Xiao YANG2, Huan-ran TAN3. Department of Pharmacology, School of Basic Medical science, peking university {3. science center, beijing 100083 2Institute of Biotechnology Academy ofMilitary Medical science, beijing 100071, china Department of Pharmacology School of Basic Medical Science Peking University Health Science Center Beijing 100083 China

AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knock- out mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.

关键词： animal disease model non insulin dependent diabetes mellitus type 2 diabetes mellitus glucokinase knockout mice

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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 {3. science center, 3. Xueyuan Road, beijing 100083, china 1Department of Immunology School of Basic Medical Sciences Peking University Health Science Center 38 Xueyuan Road Beijing 100083 China 1Department of Immunology School of Basic Medical Sciences Peking University Health Science Center 38 Xueyuan Road Beijing 100083 China 1Department of Immunology School of Basic Medical Sciences Peking University Health Science Center 38 Xueyuan Road Beijing 100083 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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Effects of estrogen on gastrocnemius muscle strain injury and regeneration in female rats

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Acta Pharmacologica Sinica 2004年第11期 105-110页

作者： Xin FENG, Guo-zhen LI, Sheng WANGDepartment of Occupational and Environmental health, Public health School, peking {3. health science center, beijing 100083, china

AIM: To study the effects of estrogen on muscle damage and regeneration after acute passive gastrocnemius muscle strain injury in female Sprague-Dawley rats. METHODS: Rats were divided into 5 groups: ovariectomized, strained and treated with low-dosage estradiol (20 μg/d) (Elow), treated with high-dosage estradiol (200 μg/d) (Ehigh), treated with oil placebo (Oil), strained with no ovariectomy (Strain), and sham operated with no strain and no ovariectomy (Con). Muscle damage index [plasma creatine kinase (CK)], antioxidant indexes [glutathione (GSH), Vitamin E (Vit E), total antioxidant capability (TAC)], and muscle regeneration index (desmin) were investigated at 7 d. RESULTS: The plasma CK activity increased but GSH, Vit E, and TAC levels decreased after muscle strain injury (Strain vs Con P<0.05). Plasma CK activity was the greatest while GSH, Vit E, and TAC were the lowest in the Oil group among the five groups (P<0.01). Plasma CK in the Ehigh and Strain groups was lower than that in the Elow group

关键词： estrogen skeletal muscle muscle injury antioxidant regeneration desmin

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Implantable CMOS neuro-stimulus chip for visual prosthesis

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science china(Information sciences) 2011年第4期54卷 898-908页

作者： ZHANG Xu 1,PEI WeiHua 1,HUANG BeiJu 1,WANG ShuJing 1,GUAN Ning 1,GUO Kai 1,WANG Yu 1,GUI Qiang 1,CHEN Jin 1,WANG Kai 2,WU HuiJuan 2,LI XiaoXin 2,LI Kai 3.& CHEN HongDa 1 1 State Key Laboratory on Integrated Optoelectronics,Institute of Semiconductors,Chinese Academy of sciences,beijing 100083.china 2 Department of Ophthalmology,People’s Hospital of {3. university,beijing 100044,china 3.Department of Epidemiology and Biostatistics,health science center,{3. university,beijing 100083.china 1. State Key Laboratory on Integrated Optoelectronics Institute of Semiconductors Chinese Academy of Sciences Beijing 100083 China2. Department of Ophthalmology People’s Hospital of Peking University Beijing 100044 China3. Department of Epidemiology and Biostatistics Health Science Center Peking University Beijing 100083 China

A prototype chip with 2×2 pixels for implanting in blind patients affected by outer retinal degeneration is presented in this *** visual prosthesis chip imitates the degenerated photoreceptor cells,senses the incident light and stimulates the remaining healthy layers of retina or optic *** pixel integrates photodiode and stimulus pulse generator,converting the illumination on the eyes into 3.bit resolution bi-phasic current ***-chip charge cancellation modules are used to discharge each electrode site for tissue *** prototype chip is designed and fabricated in 0.18-μm N-well CMOS (complementary metal oxide semiconductor) 1P6M Mix-signal process,with a ±2.5 V dual voltage *** functionality of the fabricated chip is demonstrated on anesthetized *** responses in visual cortex are successfully evoked by the neuro-stimulus chip through an on-board trigger interface and flexible electrode.

关键词： biomedical microelectronics visual prosthesis functional electrical stimulation acute animal ex- periment electrical evoked potential (EEP) test

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A quantification model for apoptosis in mouse embryos in the early stage of fetation

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science china(Life sciences) 2009年第10期52卷 922-927页

作者： WANG PengFei1, FU JianHua1, MA WanYun1, CHEN DieYan1, Lü DanYu2 & BAI WenJia3.1 Key Laboratory for Atomic and Molecular Nanosciences of Education Ministry, Department of Physics, Tsinghua university, beijing 100084, {3. 2 Department of Anatomy & Histology and Embryology, School of Basic Medical sciences peking university health science center, beijing 100083, {3. 3.Department of Automation, Tsinghua university, beijing 100084, {3. 1. Key Laboratory for Atomic and Molecular Nanosciences of Education Ministry Department of Physics Tsinghua University Beijing 100084 China 2. Department of Anatomy & Histology and Embryology School of Basic Medical Sciences Peking University Health Science Center Beijing 100083 China 3. Department of Automation Tsinghua University Beijing 100084 China

Apoptosis is the most important inducement and modulator for embryos in the early stage of fetation, i.e. after the 8-cell stage, mostly the morula and blastula stage, to proceed to the stage of nonlinear development. Using a two-photon laser scanning microscopy (TPLSM) system, we obtained 3.dimensional (3.) fluorescent images of preimplantation mouse embryos. A model for quantification was established. The statistical results for the spatial location of apoptosis bodies in embryos was obtained following image processing, as well as investigation of the kinetics of apoptosis. It was found that most (70%) apoptosis occurred in the trophectoderm, and the departure between the centroid and geometric center of embryos had a step transition when embryos developed into the 3.-cell stage, which was consistent with the theoretical prediction that the blastocele would induce a symmetry break of the distribution of cells in embryos.

关键词： apoptosis preimplantation mouse embryo TPLSM quantification model

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Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms

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Acta Pharmacologica Sinica 2004年第11期 3-11页

作者： Zhi-bin LIN, Hui-na ZHANGDepartment of Pharmacology, School of Basic Medical sciences, peking university {3. science center, beijing 100083, china

Ganoderma lucidum (G lucidum) is a medicinal fungus with a variety of biological activities. It has long been used as a folk remedy for promotion of health and longevity in china and other oriental countries. The most attractive character of this kind of medicinal fungus is its immunomodulatory and anti-tumor activities. Large numbers of studies have shown that G lucidum modulate many components of the immune system such as the antigen-presenting cells, NK cells, T and B lymphocytes, The water extract and the polysaccharides fraction of G lucidum exhibited significant anti-tumor effect in several tumor-bearing animals mainly through its immunoenhancing activity. Recent studies also showed that the alcohol extract or the triterpene fraction of G lucidum possessed anti-tumor effect, which seemed to be related to the cytotoxic activity against tumor cells directly. Preliminary study indicated that antiangiogenic effect may be involved antitumor activity of G lucidum.

关键词： Ganoderma lucidum polysaccharides triterpene immunomodulatory activities anti-tumor activities

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Distinct actions of intermittent and sustained β-adrenoceptor stimulation on cardiac remodeling

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science china(Life sciences) 2011年第6期54卷 493-501页

作者： MA XiaoWei1,3.SONG Yao1,3.CHEN Chao1,3.FU YongNan1,3.SHEN Qiang2,3.LI ZiJian1,3.& ZHANG YouYi1,3.1Institute of Vascular Medicine,peking university Third Hospital,beijing 100191,{3. 2Institute of cardiovascular science,peking university,beijing 100191,{3. 3.ey Laboratory of Molecular cardiovascular sciences,Ministry of Education,beijing 100191,{3. 1. Institute of Vascular Medicine Peking University Third Hospital Beijing 100191 China3. Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing 100191 China2. Institute of Cardiovascular Science Peking University Beijing 100191 China

Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathological cardiac ***,chronic administration of the β-AR agonist isoproterenol (ISO) has been most commonly used to model β-AR-induced cardiac ***,it remains unclear whether β-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a β-***,we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in *** were administered 5 mg (kg d)-1 ISO for 2 weeks either by daily subcutaneous injection,or continuous infusion via an implanted osmotic *** function and remodeling were determined by echocardiography,micromanometry and ***,Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes *** sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%,respectively).However,mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic *** disparity in results between the delivery methods is suggested to be due,at least in part,to increased expression of fibrogenic factors,including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4),in mice receiving intermittent application of *** summary,compared with sustained exposure to a β-AR agonist,intermittent β-AR stimulation leads to more severe cardiac dysfunction and *** findings not only further our understanding of β-AR function in the setting of cardiac pathophysiology,but also highlight that significant differences can result dependent upon the mod

关键词： β-adrenoceptor reactive oxygen species NADPH oxidase cardiac hypertrophy cardiac fibrosis

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Estimating surface evapotranspiration using combined MODIS and CBERS-02 data

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science china(Technological sciences) 2005年第S2期48卷 145-160页

作者： XIN Xiaozhou1,2, LIU Qinhuo1, TANG Yong1,3. TIAN Guoliang1, GU Xingfa1, LI Xiaowen1,2, ZHENG Hongsheng4 & CHEN Jiayi4 1. State Key Laboratory of Remote Sensing science, Institute of Remote Sensing Applications, Chinese Academy of sciences, beijing 100101, {3. 2. Research center for Remote Sensing and GIS, Department of Geography, beijing Normal university, beijing 100875, {3. 3. Graduate university of Chinese Academy of sciences, beijing 10003., {3. 4. Department of Atmospheric Physics, {13. university, beijing 100871, {3. 1. State Key Laboratory of Remote Sensing science Institute of Remote Sensing Applications Chinese Academy of Sciences 100101 Beijing China2. Research Center for Remote Sensing and GIS Department of Geography Beijing Normal University 100875 Beijing China3. Graduate University of Chinese Academy of Sciences 100039 Beijing China4. Department of Atmospheric Physics Peking University 100871 Beijing China

Spatial scale error is one of the most serious problems in the estimates of land surface heat fluxes of sensible and latent from satellite-borne data such as MODIS 1km resolution reflectance and emissive data. One of the feasible and economic ways to decrease the spatial scale error is to use high resolution land use class data together with the MODIS data. CBERS-02 data were used to produce land use class of Baiyangdian area, Hebei Province, china in the autumn of 2004. The area ratio of each class in MODIS pixel was calculated, and used to derive the heat fluxes of the mixed pixel. The results showed that the estimated heat fluxes of soil, sensible and latent have been changed remarkably after using the high resolution land class data. It could be concluded from the comparison between simulated and ground-measured fluxes as well as the theoretical analysis that high resolution land class data are useful to diminishing the scale error of heat fluxes estimated from low resolution satellite data.

关键词： surface evapotranspiration spatial scale error MODIS CBERS land class.

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