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Acta Pharmacologica Sinica 2005年第8期26卷 963-968页

作者： Min YANG~2, Qing-jun MA~(2,4), Geng-ting DANG~2, Kang-tao MA~3. Ping CHEN~3. Chun-yan ZHOU~(3.4) ~2department of Orthopedics, peking university third hospital,{3. ~3.0} of Biochemistry and Molecular Biology, School of Basic Medical Sciences, peking university Health Science Center,{3. department of Orthopedics Peking University Third Hospital Beijing China department of Biochemistry and Molecular Biology School of Basic Medical Sciences Peking University Health Science Center Beijing China

Aim: To investigate the effects of bone morphogenetic protein-7 (BMP7)-expressing recombinant adeno-associated virus (AAV) vector on the differentiation of C2C12 cells. Methods: AAV-BMP7 was packaged by infecting the stable cell clone BHK-21 (integrated with recombinant AAV vector plasmid pSNAV-BMP7) with recombinant herpes simplex virus type 1, which expresses AAV-2 Rep and Cap and possesses AAV packaging functions. Following infection with AAV-BMP7 at multiplicities of infection of lx 10～5 vector genomes per cell and subse-quent culture, C2C12 cells were assessed qualitatively for BMP7 production, alka-line phosphatase activity, osteocalcin production and Cbfal and MyoD expression. Results: C2C12 cells transduced with AAV-BMP7 could produce BMP7 protein until d 28. Alkaline phosphatase in the cultured C2C12 cell lysate was elevated. Secreted osteocalcin in the culture medium was detectable at d 12 and Cbfal mRNA expression level was upregulated, coinciding with downregulation of MyoD in a temporal manner. Conclusion: The present in vitro study demonstrated that AAV-BMP7 could infect and efficiently convert C2C12 cells from myoblasts into osteoblast lineage cells.

关键词： C2C12 adeno-associated virus bone morphogenetic protein-7 gene therapy

Up-regulation of Cartilage Oligomeric Matrix Protein Gene Expression by Insulin-like Growth Factor-Ⅰ Revealed by Real Time Reverse Transcription-Polymerase Chain Reaction

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Acta Biochimica et Biophysica Sinica 2006年第10期38卷 677-682页

作者： Hua TIAN~(1,2*) Ioannis STOGIANNIDIS~2 1 department of Orthopaedics,peking university{3.,beijing 1.0083.china 2 Coxa hospital for Joint Replacement,Biokatu 6 b,Tampere 3.101,Finland department of Orthopaedics Peking University Third HospitalBeijing 100083 China Coxa hospital for Joint Replacement Biokatu 6 bTampere 33101 Finland

Cartilage oligomeric matrix protein (COMP) strengthens cartilage by binding to type Ⅱ and typeⅨ collagen-forming bridges between collagen *** was hypothesized that perhaps one or more anabolicgrowth factors such as insulin-like growth factor-Ⅰ (IGF-Ⅰ),fibroblast growth factor-1 (FGF-1) or plateletderived growth factor-BB (PDGF-BB) increase COMP gene *** effects on primary humanchondrocytes and the chondrogenic cell line ATDC5 were studied using real time reverse transcript-poly-merase chain reaction (RT-PCR) for ***-Ⅰ,but not the FGF-1 or PDGF-BB,up-regulatedCOMP gene expression by approximate 5-fold in human adult chondrocytes in a dose-and ***-Ⅰ exerted similar effects on ATDC5 *** from these real time RT-PCR experimentswere confirmed by transfecting into ATDC5 cells a full-length mouse COMP promoter cloned upstream of aluciferase reporter *** stimulation with IGF-Ⅰ,the luciferase reporter activity increased by about *** conclusion,IGF-Ⅰ seems to be an important positive regulator of COMP,which may play animportant role in an attempted repair of either traumatized or degenerated cartilage.

关键词： cartilage oligomeric matrix protein (COMP) insulin-like growth factor-Ⅰ(IGF-Ⅰ) gene expression

Petrogenesis of Songshugou dunite body in the Qinling orogenic belt, Central china: Constraints from geochemistry and melt inclusions

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Science china Earth Sciences 2005年第8期48卷 1146-1157页

作者： SU Li1,2, SONG Shuguang3.& ZHOU Dingwu1 1. Key Laboratory of Continental Dynamics of the Ministry of Education, department of Geology, Northwestern university, Xi’an 710069, china 2. The Geological Lab Center, china university of Geosciences (beijing), beijing 1.0083. china 3. Key Laboratory of Orogenic Belts of the Ministry of Education, department of Geology, peking university, beijing 100871, china Key Laboratory of Continental Dynamics of the Ministry of Education Department of Geology Northwestern University Xi’an China The Geological Lab Center China University of Geosciences (Beijing)Beijing China Key Laboratory of Orogenic Belts of the Ministry of Education Department of Geology Peking University Beijing China

The Songshugou dunite body, which occupies an area of about 20 km2, is the largest ultramafic massif in the eastern Qinling orogenic belt, Central china. The major compo-nent of this body is dunitic rocks including mylonitic dunite and coarse-grained dunite; they oc-cupy about 95 vol% of the total body. Petrography, mineral composition, major and trace ele-ments and primitive melt inclusions have been investigated in this paper; all revealed that this dunite body is the product of melt-rock interaction by porous percolation flow. In comparison with dunite sills or veins in harzburgite from the basal part of Oman ophiolite, this dunite body is characterized by lower contents of Al2O3. CaO and HREE but higher content of highly incom-patible elements and Zr and Hf. The LREE enriched patterns and primitive mantle normalized spidergrams of trace elements are also different from the Oman dunite. Combining with melt in-clusions observed in olivines, we conclude that this dunite body is the product of large- scale porous percolation flow of high-MgO melts within depleted mantle peridotites. The high-MgO magma, in essence, was most probably produced at the hot head of an upwelling mantle plume. The occurrence of the Songshugou dunite body is closely associated with the activity of mantle super-plume in Neo-Proterozoic era in the Yangtze Craton.

关键词： Songshugou dunite body, geochemistry, melt inclusion, mantle plume, Qinling orogenic belt.

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Dehydration melting of solid amphibolite at 2.0 GPa: Effects of time and temperature

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Science china Earth Sciences 2005年第8期48卷 1120-1133页

作者： ZHOU Wenge1, XIE Hongsen1, LIU Yonggang1, ZHENG Xiaogang1, ZHAO Zhidan2 & ZHOU Hui3.1. Laboratory of Material in the Earth’s Interior, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550002, china 2. department of Geology, china {3. of Geosciences, beijing 1.0083. china 3. department of Geology, peking university, beijing 100871, china Laboratory of Material in the Earth’s Interior Institute of Geochemistry Chinese Academy of Sciences Guiyang China department of Geology China University of Geosciences Beijing China department of Geology Peking University Beijing China

Two sets of dehydration-melting with a natural solid amphibolite, collected from North Himalayan structure zone, Tibet, have been carried out in multi-anvil apparatus at 2.0 GPa and 800―1000℃, for 12―200 h. One is keeping the pressure at 2.0 GPa and the annealing time of 12 h, changing the temperature (800―1000℃). The other is keeping the pressure at 2.0 GPa and temperature at 850℃, varying the annealing time (12―200 h). The products are inspected with microscope and electron probe. The results indicate that at 2.0 GPa, annealing time of 12 h, garnets, melts and clinopyroxenes occur in amphibolite gradually with increasing temperature and the chemical compositions of melt vary from tonalite to granodiorite, and then to tonalite. However, at 2.0 GPa and 850℃, with the annealing time increasing, the garnets, melts and cli-nopyroxenes also occur in amphibolite gradually and the chemical compositions of melt vary from tonalite to granodiorite. In both cases, melts interconnect with each other when the contents of melt are over the 5 vol.%. the viscosities of the melt produced in amphibolite at temperature higher than 850℃ are on a level with 104 Pa·s. The interconnected melt with such a viscosity may segregate from the source rock and form the magma over reasonable geological time. Therefore, it is believed that at the lower part of the overthickened crust, the tonlitic and grano-dioritic magma may be generated through the dehydration melting of amphibolite.

关键词： solid amphibolite, high pressure, high temperature, time, partial melting.

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Population pharmacokinetic model of valproate and prediction of valproate serum concentrations in children with epilepsy

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Acta Pharmacologica Sinica 2004年第12期25卷 10-17页

作者： De-chun JIANG, Li WANG2 department of Pediatrics, peking university First hospital, TherapeuticDrug Monitoring and Clinical Toxicology, Center of peking university, beijing 10003., china department of Pediatrics Peking University First Hospital Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University 北京 100034

AIM: Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. METHODS: Two hundred epileptic children, whose VPA serum concentrations were collected, were divided randomly into two groups (A and B, n=100 each). The PPK parameter values of group A were calculated to establish a PPK Model by using the NPEM Program of USC*PACK software. Based on it, VPA serum concentrations of group B were predicted with the Bayesian Fitting Program of the USC*PACK software. To assess the accuracy and precision of prediction, a paired-comparisons t-test was run between predicted and ob- served concentrations, and then the mean prediction error (MPE), mean square prediction error (MSPE), root mean square prediction error (RMSPE), and coincidence rates for different percentages of prediction error were all calculated. RESULTS: Optimum PPK parameters were: Ka, 2.522±2.743.h-1; Vs, 0.3.9±0.496 L/kg; and Kel, 0.043.±0.03.4 h-1. For group B, there was no significant difference between predicted and observed concentrations. MPE was -0.43.mg/L, MSPE was 115.40 (mg/L)2, and RMSPE was 5.47 mg/L. The coincidence rates for percent- ages of prediction error, which were less than 5 %, 10 %, 15 %, 20 %, 25 %, and 3. %, were 62 %, 74 %, 82 %, 85 %, 89 %, and 93.%, respectively. CONCLUSION: A PPK model of VPA in epileptic children was successfully established. Based on it, VPA serum concentrations can be predicted accurately with a Bayesian approach.

关键词： pharmacokinetics valproic acid epilepsy Bayes theorem USC*PACK software

Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence

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Acta Pharmacologica Sinica 2005年第11期26卷 1290-1296页

作者： Li-ping ZHANG, Li WANG~2 department of Pediatrics, peking university First hospital, {3. 10003., china department of Pediatrics Peking University First Hospital Beijing China

Aim: Anticonvulsant tolerance and dependence are two obstacles that restrict the clinical use of benzodiazepines (BDZ). In order to explore the mechanism of these two adverse reactions, changes of neuropeptide Y (NPY) and its receptors in the hippocampus of rat models, in relation to flurazepam (FZP, a member of BDZ) tolerance and dependence, were investigated. Methods: The mRNA of preproNPY and its receptors (Y1, Y2, and Y5) in the hippocampus were determined by competitive RT-PCR, and the distribution of NPY in the hippocampus was examined by immunohistochemistry. Results: A decrease of preproNPY mRNA in the hippocampus was found in tolerant and dependent rats. The level of preproNPY mRNA in the hippocampus was reversely correlated with the degree of tolerance and dependence, measured by the threshold of pentylenetetrazol-induced seizures. Immunohistochemistry indicated a decrease of NPY-immunoreactive material in neurons of the CA1, CA3. and dentate gyrus regions of both tolerant and dependent rats. The mRNA of NPY receptors Y,and Y5decreased in tolerant rats but did not change in dependent rats. The mRNA of NPY receptor Y2increased in tolerant rats but decreased in dependent rats. Conclusion: A decrease of NPY in the hippocampus might be involved in anticonvulsant tolerance and dependence following long-term treatment with FZP. Y,, Y2, and Y5mRNA were also altered in FZP tolerance and dependence.

关键词： benzodiazepines neuropeptide Y flura zepam

AICAR inhibits proliferation and induced S-phase arrest,and promotes apoptosis in CaSki cells

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Acta Pharmacologica Sinica 2007年第12期28卷 1984-1990页

作者： Tong-ju GUAN~2,Feng-jin QIN~3.Jian-hai DU~4,Li Geng~3.You-yi ZHANG~(4,5),Min LI~(2,5)~2 Institute of Pathology,The School of Basic Medicine,Lanzhou university,Lanzhou 73.000,china ~3.department of Gynaecology andObstetrics,{3. university third hospital,beijing 1.0083.china ~4 Institute of Vascular Medicine,{3. university third hospital andKey Laboratory of Molecular Cardiovascular Sciences Ministry of Education,beijing 1.0083.china Institute of Pathology The School of Basic Medicine Lanzhou University Lanzhou China department of Gynaecology and Obstetrics Peking University Third Hospital Beijing China Institute of Vascular Medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing China

Aim:The aim of the present study was to determine the effect of 5-aminoimidazole-4-carboxamide-ribonucleoside （AICAR） on proliferation,cell cycle,and apoptosisin the human epithelial cervical cancer cell line CaSki ***:Cell countand 3.（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay were usedto determine cell proliferation and *** 3.258 staining was con-ducted to distinguish the apoptotic *** cycle and Annexin-V/propidiumiodide staining were analyzed by fluorescence-activated cell sorting （FACS）.AWestern blot assay was used to evaluate the expression of AKT （also known asprotein kinase B）,mammalian target of rapamycin （mTOR）,p53.and extracellularsignal-regulated kinase （ERK）.Results:AICAR （500 μmol/L） significantly inhibi-ted the proliferation of CaSki cells treated for 24,48,and 72 h as determined by *** cells at the G1and G2phases were dramatically decreased while cells atthe S phase were increased in response to AICAR treatment for 24,48,and 72 *** MTT assay showed less viable cells and Hoechst fluorescent staining showedmore apoptotic cells upon AICAR *** results of the Annexin-Vstaining demonstrated a time-dependent increase of apoptosis in cells treatedwith AICAR for 24,3.,and 48 ***,AICAR activated caspase-3.in atime-dependent *** was also found that AICAR inhibited the phosphory-lation of AKT and mTOR,which are important kinases regulating cell growth *** stimulation obviously increased the expression of the tumorsuppressor p53.and the phosphorylation of ***:AICAR inhibitedproliferation and induced S phase arrest and promoted apoptosis in CaSki cells,which might be mediated by the downregulation of the AKT/mTOR pathway andthe upregulation of the p53.ERK pathway.

关键词： AICAR proliferation apoptosis CaSki cells

Beneficial metabolic effects of nateglinide versus acarbose in patients with newly-diagnosed type 2 diabetes

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Acta Pharmacologica Sinica 2007年第4期28卷 534-539页

作者： Hong-wei GAO Chao XIE Hai-ning WANG Yu-jing LIN Tian-pei HONG department of Endocrinology,peking university{3.,beijing 1.0083.china department of Endocrinology Peking University Third Hospital Beijing China

Aim:To investigate the acute and chronic effects of nateglinide versus acarboseon plasma asymmetric dimethylarginine (ADMA) levels and lipid profiles inpatients with newly-diagnosed type 2 ***:A crossover trial ofnateglinide and acarbose was conducted on 16 drug-nave patients with newly-diagnosed type 2 diabetes during a total period of 9 *** glucose,seruminsulin,free fatty acids (FFA),lipids and lipoproteins,and plasma ADMA ***:The efficiencies of a single dose of nateglinide (120 mg) andacarbose (50 mg) for lowering postprandial hyperglycemia were ***-pared to acarbose,nateglinide significantly increased postprandial insulin releaseafter a standard meal test in patients with type 2 *** acutelydecreased postprandial 120 min FFA concentrations and 240 min ADMA levelsmore significantly than *** fasting high-density lipoprotein choles-terol level increased and the low-density lipoprotein cholesterol level decreasedsignificantly,but the fasting levels of triglycerides,total cholesterol,and ADMAwere unchanged after 4 weeks of treatment with *** did notaffect fasting lipid profiles or the ADMA levels after 4 weeks of ***:These results suggest that the reduction of postprandial FFA andADMA concentrations induced by nateglinide may be associated with the partialrestoration of early-phase insulin secretion and may impart a cardiovascularadvantage in comparison with acarbose.

关键词： nateglinide acarbose free fatty acids asymmetric dimethylarginine

L~∞ CONVERGENCE OF QUASI-CONFORMING FINITE ELEMENTS FOR THE BIHARMONIC EQUATION

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Journal of Computational Mathematics 1995年第2期13卷 108-122页

作者： Wang Ming (department of Mathematics, peking university, beijing, {3.) 北京大学数学系北京

In this paper we consider the L∞ convergence for quasi-conforming finite ele-ments solving the boundary value probzlems of the biharmonic equation and give the nearly optimal order L∞ estimates.

关键词：双调和方程拟共形有限元 L↑∞收敛性 L↑∞估计

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Oblique Derivative Problems for Second OrderNonlinear Equations of Mixed Type inMultiply Connected Domains

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Communications in Nonlinear Science and Numerical Simulation 1999年第4期4卷 281-284页

作者： Guochun WEN(department of Mathematics, peking university, beijing 100871, {3.) department of Mathematics Peking University Beijing 100871 China

1FormulationoftheProblemLetDbeNconnectedboundeddomaininthecomplexplaneCwiththeboundaryNZNOD=WUL,wherer=ZrjEn（00},L=ULi’andrhastheendj=1j=1poiatsal=0 详细信息

1FormulationoftheProblemLetDbeNconnectedboundeddomaininthecomplexplaneCwiththeboundaryNZNOD=WUL,wherer=ZrjEn（00},L=ULi’andrhastheendj=1j=1poiatsal=0

关键词： oblique derivative problems quasinonlinear equations of mixed type mul-tiply connected domains.