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Sequencing of phosphopeptides sulfonated by 4-sulfophenyl isothiocyanate using post-source decay matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

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Progress in Natural Science:Materials International 2006年第9期16卷 930-935页

作者： TANG Jianguang , WANG Yongjun , ZHANG Hainan, WANG Chunyu, HU Zhiping, XUE Zhigang, XIA Kun3 and SHI Xiaoliu ( Department of Neurology, the second xiangya hospital, Central South University, Changsha 410011, China Department of Digestion, the second xiangya hospital, Central South University, Changsha 410011, China National Key Laboratory of Chinese Genetics, Changsha 410078, China) Department of Neurology The Second Xiangya Hospital Central South University Changsha 410011 China Department of Digestion The Second Xiangya Hospital Central South University Changsha 410011 China National Key Laboratory of Chinese Genetics Changsha 410078 China

Phosphorylation/dephosphorylation is probably the most common and important reversible post-translational modification of proteins. Analyzing the functional effects of phosphorylation is helpful for understanding the biological functions of proteins. Identification of the phosphorylation sites of phosphorylated protein is a prerequisite for research on phosphorylation. In this work, an effective and simple method of identification of protein phosphorylation sites has been developed. Phosphopeptides were selectively enriched with immobilized metal affinity chromatography (IMAC) and subsequently chemically modified by 4-sulfophenyI isothiocyanate, and then the chemically modified phosphopeptides were sequenced with post-source decay (PSD) matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry for detecting phosphorylation sites. The charge of derivatization by 4-sulfophenyl isothiocyanate introduces a negative sulfonic acid group at the N-terminus of a peptide, and enables the selective detection of only a single series of C-terminal y-type ions. This chemically assisted method greatly simplifies the extremely complex pattern of PSD fragment ions and makes the PSD spectra more easier to be interpreted. The phosphorylation sites of a synthesized model phosphopeptide and human c-myc protein have been successfully identified by this method.

关键词： phosphopeptides sequencing 4-sulfophenyl isothiocyanate post-source decay matrix-assisted laser desorption/ion-ization time-of-flight mass spectrometry.

Potential role of retina as a biomarker for progression of Parkinson's disease

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International Journal of Ophthalmology(English edition) 2011年第4期4卷 433-438页

作者： Tian Tian 1, Xiao-Hua Zhu 2, Yun-Hai Liu 1 1Department of Neurology, xiangya hospital, Central-South University, 87 xiangya Road, Changsha 410008, Hunan Province, China 2Department of Ophthalmology, the second xiangya hospital, Central-South University, 139 Renmin Middle Road, Changsha 410011, Hunan Province, China Department of Neurology Xiangya Hospital Central-South University 87 Xiangya Road Changsha 410008 Hunan Province China.

Optical coherence tomography (OCT) noninvasively quantifies the thickness of the retinal nerve fiber layer (RNFL). OCT has been studied in several neuro-ophthalmic conditions, including Parkinson’s disease (PD). Recent studies suggest that the quantitative analysis of RNFL can be precisely and noninvasively done by OCT scans and the results suggest that the thickness of RNFL is significantly decreased in patients with PD compared with age-matched controls and the foveal retinal thickness correlates with disease severity in PD. In this article, the application of OCT imaging of the retina in PD was reviewed. Literature survey of PubMed was carried out using the search terms of "Optical Coherence Tomography" combined with "Parkinson’s Disease" and "retinal nerve fiber layer" (without restriction to the year of publication). Some related articles were also included. The search was completed in Jul. 2011 and revised and updated as necessary. The aim of this article is to review the current literatures on the use of optical coherence tomography in patients affected by PD and to enhance its use in clinical practice in neuro-ophthalmology.

关键词： Parkinson disease optical coherence tomography retinal nerve fiber layer thickness

Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia

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Acta Pharmacologica Sinica 2006年第3期27卷 381-386页

作者： Zhi-ling ZHOU~2 Xin LI~3 Huai-yan PENG~4 Xi-yong YU~2 Ming YANG~2 Feng-li SU~1 Feng WANG~1 Rong-hua ZHU~1 Chun-yu DENG~2 Qiu-xiong LIN~2 Chuan-yue WANG~5 Wen-biao LI~5 Shu-guang LIN~2 Huan-de LI~(1,6) ~1Clinical Pharmacy Research Institute,xiangya second hospital,Central South University,Changsha 410011,China ~2Research Center of Medical Science,Guangdong Provincial People's hospital,Guangzhou 510080,China ~3Vascular Surgery Department,xiangya second hospital,Central South University,Changsha 410011,China ~4Department of Clinical Laboratory,Third xiangya hospital,Central South University,Changsha 410013,China ~5Affiliated Beijing An Ding hospital,Capital University of Medical Science,Beijing 100088,China Research Center of Medical Science Guangdong Provincial People's Hospital Guangzhou China Vascular Surgery Department Xiangya Second Hospital Central South University Changsha China Department of Clinical Laboratory Third Xiangya Hospital Central South University Changsha China Clinical Pharmacy Research Institute Xiangya Second Hospital Central South University Changsha China Affiliated Beijing An Ding hospital Capital University of Medical Science Beijing China

Aim:To study the multiple dose clinical pharmacokinetics of risperidone and itsmain active metabolite,9-hydroxyrisperidone,in Chinese female patients ***:The subjects were 23 Chinese female inpatients aged18-65 years who met the CCMD-Ⅲ（third revision of the Chinese Criteria of Men-tal Disorders）criteria for *** were tested after 17 d of treat-ment with 2 mg risperidone twice *** concentrations of risperidone and9-hydroxy-risperidone were assayed by using validated high performance liquidchromatography-mass spectrometry（HPLC-MS）***:Risperidonewas rapidly absorbed(Tmaxwas 1.6 h)and its T1/2in plasma was short（3.2 h）.9-hydroxy-risperidone was quickly metabolized from the parent drug with a meanTmaxof 2.5 *** had a long half-life of 24.7 *** Cavssof risperidone and 9-hydroxy-risperidone were 36.9±33.1 and 110.6±30.5 μg·h·L-1,respectively,and the AUC0-12sswere 443.2+397.4 and 1327.2±402.3 μg·h·L-1,***/F and V/F ofrisperidone were 8.7±6.2 L/h and 34.1±24.3 L,*** varia-tions for pharmacokinetic parameters were quite large for *** 23 sub-jects experienced high prolactin levels when treated with *** was no correlation between prolactin level and the concentration ofrisperidone,9-hydroxy-risperidone,or the active ***:Risperidoneshowed large interindividual variations in *** ofrisperidone resulted in high serum prolactin *** results indicate that sys-temic exposure to risperidone and 9-hydroxy-risperidone in female Chinese schizo-phrenic patients is higher relative to published data for white Caucasian *** studies regarding the PK/PD relationship may be required to develop areasonable clinical dosage regimen for Chinese female patients.

关键词： pharmacokinetics risperidone 9-hydroxyrisperidone schizophrenia

Multiple dose pharmacokinetics of quetiapine and some of its metabolites in Chinese suffering from schizophrenia

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Acta Pharmacologica Sinica 2004年第3期25卷 136-140页

作者： Kun-yan LI,Xin LI,Ze-neng CHENG,Wen-xing PENG,Bi-kui ZHANG,Huan-de LI1 Clinic Pharmacy Research Institute,xiangya second hospital,Central South University,Changsha 410011,China Clinic Pharmacy Research Institute Xiangya Second Hospital Central South University Changsha 410011

AIM: To study the multiple dose pharmacokinetics of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N- dealkyl-metabolites in Chinese suffering from schizophrenia. METHODS: Twenty-one patients (11 females and 10 males) were given quetiapine twice daily to control the symptoms. After the dose reached 200 mg twice daily, blood were sampled to study the pharmacokinetics. The plasma concentrations of quetiapine and its metabolites were assayed by HPLC-MS. RESULTS: The main pharmacokinetic parameters of quetiapine, 7-hydroxy-N-dealkyl- quetiapine, quetiapine sulfoxide, and 7-hydroxy-quetiapine were as follows: tmax were 2.0 (0.3-5.0), 4.0 (1.5-6.0), 3.0 (0.5-5.0), and 3.0 (0.5-5.0) h respectively; t1/2 were (7±3), (9.4±2.7), (7±3), and (8±5) h, respectively; Cm SS ax were (678±325), (19±5), (451±216), and (58±22) μg/L, respectively; CSS were (51±68), (3.3±1.6), (35±36), and min (5±4) μg/L, respectively; Cav were (295±144), (13±4), (209±71), and (28±9) μg/L, respectively; AUC0?12 were SS SS (3 538±1 728), (153±44), (2 512±854), and (335±104) μg·h·L-1, respectively; AUC0 were (5 534±4 198), (287±107), SS -∞ (3 858±2 012), and (529±262) μg·h·L-1, respectively; Ke were (0.11±0.03), (0.079±0.019), (0.11±0.03), and (0.103±0.028) h-1, respectively; CL/F and V/F of quetiapine were (67±25) L·h-1 and (672±394) L, respectively. The plasma concentrations for the four compounds reached a steady state within 48 h at the dose of 200 mg initiation. These parameters were not statistically different between genders. CONCLUSIONS: Quetiapine was absorbed quickly, distributed widely, and metabolized mainly to be quetiapine sulfoxide. The elimination speeds of quetiapine and its three metabolites were similar. Gender had no effect on the pharmacokinetics of quetiapine and its metabolites. The clinical dosage regime caused no drug accumulation.

关键词： quetiapine pharmacokinetics metabolism schizophrenia Chinese

GPC3 fused to an alpha epitope of HBsAg acts as an immune target against hepatocellular carcinoma associated with hepatitis B virus

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Hepatobiliary & Pancreatic Diseases International 2011年第2期10卷 164-170页

作者： Jun-Wen Yang,Dong-Ye Yang,Fang-Gen Lu,Cai-Hong Li,Hui Chen,Ning Xie and Xin Zhao Department of Digestive Diseases,second xiangya hospital,Central South University,Changsha 410011,China Department of Digestive Diseases Second Xiangya Hospital Central South University Changsha 410011 China

BACKGROUND:The incidence of hepatocellular carcinoma (HCC)in China is closely related to the population infected with hepatitis B virus(HBV).HCC cells with HBV secrete soluble HBsAg into blood but do not express it on the cell membrane This study aimed to construct and investigate a new glycosyl phosphatidylinositol(GPI)-anchored protein(GPC3+α+EGFP) as a DNA vaccine against HCC associated with HBV. METHODS:A recombinant plasmid(pcDNA3.1(+)/GPC3+ α+EGFP)was constructed and verified by restriction endo nuclease digestion and ***3.1(+)/GPC3+α+ EGFP was transfected into HepG2 cells(experimental group) using lipofectamine ***-N1-transfected HepG2 cells were used as a negative control,and non-transfected HepG2 cells sreved as a blank ***2 cells that steadily expressed the fusion protein GPC3+α+EGFP were screened by G418,propagated,and co-cultured with lymphocytes from healthy *** proliferation was measured by the classic sulforhodamine B *** was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL),and Fas gene transcription was determined by quantitative fluorescent PCR. RESULTS:The pcDNA3.1(+)/GPC3+α+EGFP plasmid was successfully *** the experimental group,green fluorescence was observed at the cell periphery and in the cytoplasm,whereas in the negative control group,fluorescence was evenly distributed throughout the *** of the experimental group significantly decreased after 72 hours compared to the negative and blank control ***,the number of apoptotic cells was statistically different among the three groups as determined by a contingency table Chisquare test;the experimental group had the highest incidence of *** gene transcription in the experimental group was higher than in the two control groups,and an increasing trend with time in the experimental group was observed. CONCLUSION:A chimeric,membrane-anchored protein, GPC3+α+EGFP,localized

关键词： HBsAg-αepitope glypican 3 hepatocellular carcinoma hepatitis B virus protein engineering

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Immunoglobulin M Levels Inversely Correlate with CD40 Ligand Promoter Methylation in Patients with Primary Biliary Cirrhosis

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Simultaneous determination of quetiapine and three metabolites in human plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry

中华医学会第十八次全国皮肤性病学术年会

作者： Qian-jin Lu Department of Dermatology,second xiangya hospital,Central South University

The cross-talk of cluster of differentiation(CD)40/CD40 ligand(CD40L) plays a key role in CD41 T-cell priming,B-cell terminal maturation,and immunoglobulin(Ig) class-switch *** defects in the CD40L lead to a disorder characterized by elevated concentrations of serum IgM and *** with primary biliary cirrhosis(PBC) characteristically show circulating

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Acta Pharmacologica Sinica 2004年第1期 112-116页

作者： Kun-yan LI, Ze-neng CHENG, Xin LI, Xue-lian BAI, Bi-kui ZHANG, Feng WANG, Huan-de LIClinical Pharmaceutical Research Institute, xiangya second hospital, Central South University, Changsha 410011, China

AIM: To develop a high performance liquid chromatography-electrospray mass spectrometry (HPLC-MS/ESI) method for simultaneous determination of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N-dealkyl-metabo-lites in human plasma. METHODS: The HPLC separation of the compounds was performed on a Kromasil C18, (5 urn, 4.6 mm×150 mm) column, using water (formic acid: 1.70 mmol/L, ammonium acetate: 5.8 mmol/L)-acetoni trile (65:35) as mobile phase, with a flow-rate of 0.95 mL/min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer and detected in the selected ion recording (SIR) mode. The samples were extracted using solid-phase extraction columns. RESULTS: The calibration curves were linear in the ranges of 10-2000 μg/L for quetiapine, 1-200 μg/L for its metabolites, respectively. The average extraction recoveries for all the four samples were above 85 %.

关键词： quetiapine high pressure liquid chromatography electrospray ionization mass spectrometry metabolism

Connective tissue growth faaor induces osteogenic differentiation through a Runx2 aaivation in vascular smooth muscle cells by ERK Signaling

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Connective tissue growth faaor induces osteogenic differenti...

中华医学会第十一次全国内分泌学学术会议

作者： yiqun peng he second xiangya hospital of Central South University,Changsha 410011,China

Objective Vascular calcification is an active and cellregulated process resemble to skeletal mineralization and the ERK signal pathway is *** tissue growth factor(CTGF) plays an essential role in the pathogenesis of atherosclerosi,but little is known about how CTGF affects vas- cular *** the present study we defined the molecular signaling that is operative in the CTGF-induced VSMCs calcification. Methods VSMCs used in the present studies were identi-

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增龄性记忆改变规律及影响因素的研究

心理科学 2002年第4期25卷 402-405页

作者：郑虹程灶火中南大学湘雅二医院长沙410011

本研究用多维记忆量表对 2 80名 5 0～ 91岁的老年人做了测查 ,同时收集了一般资料 ,以探讨增龄性记忆改变的规律和年龄、教育和职业等因素对增龄性记忆改变的影响。结果表明 :随年龄增长 ,各记忆组合分和分测验成绩均呈下降趋势 ,外显... 详细信息

本研究用多维记忆量表对 2 80名 5 0～ 91岁的老年人做了测查 ,同时收集了一般资料 ,以探讨增龄性记忆改变的规律和年龄、教育和职业等因素对增龄性记忆改变的影响。结果表明 :随年龄增长 ,各记忆组合分和分测验成绩均呈下降趋势 ,外显记忆成绩在 70岁后呈快速下降 ,内隐记忆和日常生活记忆在 75岁后才有明显下降 ;记忆总分、外显记忆和日常生活记忆均受年龄和教育的影响 ,内隐记忆不受教育的影响。结果提示老年人记忆随年龄增长呈渐渐下降 ,不同记忆功能开始下降的年龄和下降速率不同 ,教育对增龄性记忆改变有保护作用。

关键词：增龄性记忆老年人外显记忆成绩内隐记忆

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