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Polymorphism Analyses of Hepatitis B Virus X Gene in Hepatocellular Carcinoma Patients from Southern china

Acta Biochimica et Biophysica Sinica 2007年第4期39卷 265-272页

作者： Ping'an ZHU~(1,2*) Deming TAN~1 Zhongtian PENG~1 Fei LIU~1 Lin SONG 1 Department of Infectious Diseases,Xiangya hospital,Central South University,Changsha 410008,china 2 the seventh hospital of shenzhen,shenzhen 518081,china Department of Infectious Diseases Xiangya Hospital Central South UniversityChangsha 410008 China The seventh hospital of shenzhenshenzhen 518081 China

Chronic hepatitis B virus(HBV)infection is one of the major causes of hepatocellularcarcinoma(HCC),and the HBV X(HBx)gene plays a critical role in the molecular pathogenesis ofHBV-related *** have investigated whether there are particular HBx gene mutations associated withHCC in patients from southern *** HBx gene was examined in 51 paraffin-embedded tumor tissuesamples from patients with HCC and 25 serum samples from the HBV carrier by nested polymerase chainreaction(PCR),single-stranded conformational polymorphism and heteroduplex *** HBx geneswith potentially important mutations from tumor tissue samples were cloned,sequenced and aligned withthe published HBx gene *** genotypes in tumor tissue samples were analyzed by nested *** of HBx gene polymorphism showed that 31.3% of HBx gene fragments in tumor tissue sampleshad a special pattern.A common deletion at nt 382-400 of the HBx gene accompanied by 29 point mutationswas detected in four randomly selected tumor tissue samples with this pattern which caused a frame-shiftin the HBx open reading frame with a new stop codon at nt 1818,resulting in an HBx polypeptide chaintruncated at the C end in these *** the four randomly selected samples,three were HBV genotypeB,and one was not detected by our present *** another tumor tissue sample,amplification of thefull-length HBx gene yielded a shorter *** of this fragment revealed a 264 bp deletionbetween nt 1577 and 1840 of the HBV *** results suggest that HBx gene mutation occurs frequentlyin HCC samples,and the deletion at nt 382-400 of the HBx gene might play a role in carcinogenesis of HCCin southern china.

关键词： hepatocellular carcinoma hepatitis B virus HBx polymorphism mutation

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VEGF-specific siRNAs modified with 2′-deoxy effectively suppress VEGF expression and inhibit growth of nasopharyngeal carcinoma xenograft in a mouse model

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Science china(Life Sciences) 2008年第2期51卷 104-110页

作者： CHEN ShanYi1, GAO GuoFeng1, CHEN Wei1, Lü Qing2, TANG Shen2, HUA Zhong2, YE WenBin2, GU DaYong2, WANG ShaYan1 & ZHANG YaOu2 1 shenzhen People’s hospital, Clinical Medical College of Jinan University, shenzhen 518020, china 2 Life Science Division, Graduate School at shenzhen, Tsinghua University, shenzhen 518055, china shenzhen People’s hospital Clinical Medical College of Jinan University Shenzhen China Life Science Division Graduate School at Shenzhen Tsinghua University Shenzhen China

Vascular endothelial growth factor (VEGF) is up-regulated in the vast majority of human tumors. The up-regulation of VEGF not only plays important roles in tumor angiogenesis, but also provides a target for tumor treatment with small interfering RNA (siRNA) that targets VEGF; however, it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF. A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line. In this study, we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells, and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents. CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs. The expression of VEGF was effectively suppressed by VEGF-specific siRNAs, measured by ELISA, Western blot analysis and RT-PCR. Furthermore, experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells. VEGF-specific siRNAs were modified with 2′-deoxy, then injected into the tumors, and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs. Tumor growth was reduced significantly after 3 weeks' treatment. These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression, such as CNE, and VEGF-specific siRNAs modified with 2′-deoxy can be used as potential agents for tumor therapy.

关键词： small interfering RNA vascular endothelial growth factor (VEGF) nasopharyngeal carcinoma 2′-deoxy modification ultrasound

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Antisense oligonucleotides-induced local blockade of T-bet expression leads to airway inflammation in rats

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Acta Pharmacologica Sinica 2006年第5期27卷 561-567页

作者： Gang WANG~2 Chun-tao LIU~(3,4) Zeng-li WANG~3 Li-li JIANG~5 Cun-liang YAN~6 Feng-min LUO~3 ~2Department of Integrated Traditional Chinese and Western Medicine.West china hospital.Sichuan University,Chengdu 610041,china.~3Department of Respiratory Medicine,West china hospital,Sichuan University.Chengdu 610041.china ~5Department of Pathology,West china hospital.Sichuan University,Chengdu 610041,china:~6Department of Laboratory Medicine.shenzhen hospital,Peking University.shenzhen 518036,china Department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Chengdu China Department of Respiratory Medicine West China Hospital Sichuan University Chengdu China Department of Pathology West China Hospital Sichuan University Chengdu China Department of Laboratory Medicine Shenzhen Hospital Peking University Shenzhen China

Aim:To explore whether local blockade of T-box expressed in T cells (T-bet)expression in the lungs could lead to airway ***:Twenty-fourrats were randomly divided into 4 groups:saline group,ovalbumin (OVA)-sensi-tized group,nonsense group,and the antisense *** OVA-sensitized ratswere sensitized and challenged with OVA,and the rats in the nonsense andantisense groups were subjected to an aerosol delivery of the nonsense andantisense oligonucleotides (AS-ODN) of T-bet (0.1%,w/v).The levels of inter-feron-γ(IFN-γ),interleukin-4(IL-4),and IL-5 in the bronchoalveolar lavage fluid(BALF) were detected by ELISA,and the mRNA and the protein expression ofT-bet and GATA-3 genes were examined by in situ hybridization and Western blotanalysis,***:The expression of T-bet mRNA and protein in thelungs of the rats in the antisense group were inhibited *** lungs ofthe rats in the antisense and OVA-sensitized groups showed eosinophil and lym-phocyte inflammatory infiltration,and eosinophilia located predominantly aroundthe *** number of GATA-3 mRNA-positive cells and the level of GATA-3protein in the lungs of the rats in the antisense and the OVA-sensitized groupssignificantly *** level of IL-4 and IL-5 in the BALF in the antisenseand OVA-sensitized groups were elevated,but the level of IFN-γ ***:Antisense ODN-induced local blockade of T-bet expres-sion leads to airway inflammation with a selective alteration in patterns of cytokineexpression and recruitment of eosinophil cells similar to that in the OVA-sensitizedanimals.

关键词： airway inflammation antisense oligonucleotides GATA3 transcription factor interferon type Ⅱ interleukin-4 interleukin-5 Tbox expressed in T cells

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Synthesis and antitussive evaluation of verticinone-cholic acid salt,a novel and potential cough therapeutic agent

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Acta Pharmacologica Sinica 2007年第10期28卷 1591-1596页

作者： Fang-zhou XU~(2,3),Chang CHEN~2,Yong-hui ZHANG~2,Han-li RUAN~2,Hui-fang PI~2,Pong ZHANG~2,Ji-zhou WU~(2,4)~2 Faculty of Pharmaceutical Sciences,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,china~3 Department of Pharmacy,Peking University shenzhen hospital,shenzhen 518036,china Faculty of Pharmaceutical Sciences Tongji Medical College Huazhong University of Science and Technology Wuhan China Department of Pharmacy Peking University Shenzhen Hospital Shenzhen China

Aim:To seek a novel and potent antitussive drug based on Shedan-Chuanbeipowder,a complex of traditional Chinese medicine preparation for cough ***:Verticinone-cholic acid (Ver-CA) salt,a novel,salifying derivative ofverticinone and cholic acid,both of which are the major bioactive components inShedan-Chuanbei powder,was *** then evaluated the antitussiveactivity and the acute toxicity of the ***:The new compound,with goodsolubility in water,has much more potent antitussive activity in comparison withthe same dose of single verticinone and single cholic *** administration 3mg/kg of Ver-CA could result in over 50% reduction of a citric acid-induced *** with naloxone (0.8 mg/kg,ip) can only partially antagonize its anti-tussive *** the other hand,glybenclamide (3 mg/kg,ip),an ATP-sensitiveK~+ channel blocker,can also significantly reduce the antitussive effect of Ver-CA.A further acute toxicity study showed that the LD50values of Ver-CA were 3 timesthat of ***:Based on the studies of pharmacology and acutetoxicity,the salt has a synergic and attenuated toxicity compared with singleverticinone and cholic ***,the present study also suggests that Ver-CA,a potential novel antitussive agent,may exert its antitussive effect via boththe peripheral (modulated by ATP-sensitive K~+ channels) and central mechanisms(modulated by the opioid receptor).

关键词： verticinone-cholic acid salt Shedan-Chuanbei powder,cholic acid verticinone antitussive effect ATP-sensitive K~+ channels

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Lactate Dehydrogenase Isoenzyme of Lens in Fetus

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眼科学报 2002年第3期18卷 194-196页

作者： Kexi Ding, Yasong ZhangDepartment of Ophthalmology, Peking University shenzhen hospital, shenzhen 518036, chinaDepartment of Laboratory, Guangzhou Liuhua Bridge hospital, Guangzhou 510000, china Department of Ophthalmology Peking University Shenzhen Hospital Shenzhen 518036 China

Purpose: The LDH isoenzyme patterns were evaluated in lens of fetus to study the metabolism in human ***: LDH isoenzyme electrophoresis was performed in 15 lenses of human fetus aged from 4～6 ***: There are 5 bands of LDH in fetus lens. LDH4 lever is the highest, and LDH1 is the lowest, especially in the cortex of lens. LDH1 is higher in lens of 4 months of age than in that of 5 and 6 months of ***: LDH isoenzyme in lens of fetus shows mainly anaerobic metabolism in development, but there is also aerobic metabolism, especially in younger fetus.

关键词：胎儿晶状体乳酸脱氢酶同工酶

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基于多序列瘤周瘤内影像组学预测胶质瘤病理分级

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临床放射学杂志 2024年第9期43卷 1450-1455页

作者：刘深圳王在斌娄金峰姜帆夏熙双河南科技大学第一附属医院神经外科洛阳471000 郑州大学第二附属医院神经外科郑州450014

目的探讨多序列瘤周瘤内影像组学模型预测胶质瘤病理分级的价值。方法回顾性分析153例病理结果为胶质瘤患者的MRI影像资料,其中低级别胶质瘤50例,高级别胶质瘤103例。将预处理后的T_(1)WI、T_(2)WI、T_(2)FLAIR、T_(1)增强影像资料导入3... 详细信息

目的探讨多序列瘤周瘤内影像组学模型预测胶质瘤病理分级的价值。方法回顾性分析153例病理结果为胶质瘤患者的MRI影像资料,其中低级别胶质瘤50例,高级别胶质瘤103例。将预处理后的T_(1)WI、T_(2)WI、T_(2)FLAIR、T_(1)增强影像资料导入3D Slicer中进行瘤内感兴趣区域勾画,并将其自动外扩至肿瘤周围2 mm、3 mm、4 mm、5 mm、6 mm,应用Python中的pyradiomics进行影像组学特征提取,使用t检验、Pearson相关分析以及最小绝对收缩与选择算法模型进一步筛选特征,使用6种分类器分别构建瘤周、瘤内影像组学模型,筛选出最佳瘤周模型后,将每个序列的最佳瘤周(均为瘤周3 mm)与瘤内影像特征组合构建瘤内+瘤周模型,采用受试者工作特征曲线(ROC)及其曲线下面积(AUC)评估不同预测模型的效能,采用DeLong检验比较不同模型之间AUC的差异。结果患者的性别、年龄与胶质瘤病理分级无关(P>0.05)。在构建的预测模型中,4种序列的瘤周与瘤内影像特征联合构建的预测模型预测性能最佳,在测试组AUC达到了为0.987、准确度为0.935、特异度为0.929、敏感度为0.906。结论瘤周影像组学模型同样具有良好的预测效能,与瘤内影像组学模型效能相当,并能够提升瘤内影像组学模型的预测性能。瘤周瘤内影像组为术前确定患者胶质瘤病理分级提供一种准确率更高的无创预测方法,为临床个体化、精确化治疗方案的制定及预后评估提供重要信息。

关键词：胶质瘤病理分级影像组学瘤周脑区联合模型

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Zeus robot-assisted laparoscopic cholecystectomy in comparison with conventional laparoscopic cholecystectomy

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 115-118页

作者： Han-Xin Zhou, Yue-Hua Guo, Xiao-Fang Yu, Shi-Yun Bao, Jia-Lin Liu, Yue Zhang and Yong-Gong Ren Department of Minimally Invasive Surgery, shenzhen People’s hospital, Jinan University 2nd Clinical Medicine College, shenzhen 518020. china Department of Anesthesia, shenzhen People’s hospital, Jinan University 2nd Clinical Medicine College, shenzhen 518020, china Department of Minimally Invasive Surgery Shenzhen People's Hospital Jinan University 2nd Clinical Medicine College Shenzhen 518020 China. hxzhou55@***

BACKGROUND: The robotic surgical system overcomes many technological obstacles of conventional laparoscopic surgery, and possesses enormous clinical applied potential. The aim of this study was to compare the efficacy of Zeus robot-assisted laparoscopic cholecystectomy with conventional laparoscopic cholecystectomy. METHODS: Forty patients undergoing elective cholecystectomy were randomly divided into two groups. Patients in group A (n=20) underwent Zeus robot-assisted laparoscopic cholecystectomy, and patients in group B (n=20) received conventional laparoscopic cholecystectomy. The parameters on operative field, operative time, the number of actions, the rate of operative errors and minimal trauma were evaluated and compared between the two groups. RESULTS: The number of cleating camera (1.1±1.0 times) and the time of adjusting the operative field (2.2±0.7 minutes) in group A were significantly less than those (4.5±1.5 times) and (7.5±1.2 minutes) in group B. The number of dissection actions (337±86 times) and the rate of operative errors (10%) in group A were less than those (389±94 times), (25%) in group B. The total operation time (104.9±20.5 minutes) and setup time (29.5±9.8 minutes) in group A were significandy longer than those (78.6±17.1 minutes), (12.6±2.5 minutes) in group B. Blood loss and postoperative hospitalization were similar. No postoperative complications occurred in both groups, and open cholecystectomy was performed in each group. CONCLUSIONS: Zeus robot-assisted cholecystectomy inherits the benefits of minimally invasive surgery. The Zeus robotic surgical system is better than conventional laparoscopic technique in controlling the operative field and can be manipulated precisely and stablely though it requires more operative time.

关键词： Zeus robot-assisted cholecystectomy laparoscopy comparative study

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Specific cellular immunity and antitumor responses in C57BL/6 mice induced by DNA vaccine encoding murine AFP

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Hepatobiliary & Pancreatic Diseases International 2004年第3期3卷 440-443页

作者： Geng Tian, Ji-Lin Yi and Ping Xiong Department of Oncology, shenzhen Second hospital,shenzhen 518035, china Tongji hospital and Depart-ment of Immunology , Tongji Medical College, Huazhong Uni-versity of Science and Technology, Wuhan 430030, china Department of Oncology Shenzhen Second Hospital Shenzhen 518035 China. geng_tian707@***

BACKGROUND: The inoculation of plasmid DNA encod-ing tumor-associated antigens is a novel and powerful stra-tegy for antitumor vaccination. This study was designed toconstruct the DNA vaccine of mouse AFP and to observethe specific cellular immunologic responses and the antitu-mor responses in mice induced by this ***: The murine AFP gene was amplified by RT-PCR from total RNA extracted from Hepal-6 cells andcloned into the vector pcDNA3.1 to construct *** DNA vaccine was identified by restriction enzymeanalysis, sequencing and expression. EL-4 ( mAFP) wasdeveloped by stable transfection of EL-4 cells with *** frequency of cells producing IFN-γ in splenocytes har-vested from the mice immunized with the DNA vaccine byintramuscular injection was measured by enzyme linkedimmunospot (ELISPOT). The mice immunized with theDNA vaccine were inoculated with EL-4 (mAFP) cells inback to observe the inhibitory effect of the immunizationon tumor. On the other hand, blood samples were collect-ed from the immunized mice to check the functions of theliver and ***: The murine AFP gene was successfully clonedby RT-PCR. Results from restriction enzyme analysis, se-quencing and expression showed that the DNA vaccine wassuccessfully constructed. The expression of mAFP mRNAin EL-4 (mAFP) was confirmed by RT-PCR. The resultsof ELISPOT showed that the number of IFN-γ-producingcells of the pmAFP vaccine group was significantly higherthan that of other groups (P 2. 42 ± 123. 71 mm3 ) wassignificantly smaller than that in other groups (P<0.01).The function of mouse liver and kidney in each group ***: The successfully constructed DNA vaccineof AFP can induce specific cellular immunologic responsesand significant antitumor reponses in mouse and has no im-pact on the function of mouse liver and kindey.

关键词： DNA vaccine α-fetoprotein mouse immunotherapy

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Effects of HBV gene variations on disease development and antiviral therapy for patients with chronic hepatitis B

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Hepatobiliary & Pancreatic Diseases International 2005年第3期4卷 393-397页

作者： shenzhen Eastlake hospital, shenzhen 518020, china (Chen JY) and National Key Laboratory of Virology (Wuhan University) Department of Infectious Diseases, Renmin hospital, Wuhan University, Wuhan 430060, china(Wang LW, Sun XM and Gong ZJ) shenzhen Eastlake hospital Shenzhen 518020 China.

Viral variation may change pathogenicity, escape immunity, lead to persistence infection, and cause drug resistance against antiviral therapy. This study was undertaken to investigate the effects of HBV gene variation on the progression of disease and on the efficacy of antiviral therapy for patients with chronic hepatitis B(CHB). METHODS:Hepatitis B virus (HBV) gene mutational sites were detected using gene chip in selected hepatitis B patients. RESULTS:In the patients HBeAg did not show serologic conversion or HBeAg(-)/anti-HBe(+), but their HBV DNA remained positive 24 weeks after α-interferon therapy, which was associated with mutations of nt1896, nt1814, nt1762 and nt1764. In the patients, that HBV DNA levels decreased or were undetectable, but rebounded later after antiviral therapy by lamivudine was associated with mutations of aa528 and(or) aa552(*** mutation), which resulted in lamivudine-resistance. YMDD mutation was prone to occur 52 weeks after lamivudine therapy in some chronic hepatitis B patients (26.4%). Nt1896 mutation was common in most chronic hepatitis B patients (68.5%). Chronic severe hepatitis, cirrhosis, and primary liver carcinoma were related to the mutations of nt1896, nt1762 and nt1764. CONCLUSIONS:HBV gene mutations could aggravate patient's condition and affect the efficacy of antiviral therapy. The regular detection of HBV gene mutation is helpful for identification of disease prognosis and adjustment of therapeutic strategy.

关键词： hepatitis B virus chronic hepatitis B gene mutation antiviral therapy

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STUDY ON GLYCOCONJUGATE CHANGES ON CELL SURFACE IN PROGRESSIVE DEVELOPMENT OF PULMONARY TUMOR

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中国体视学与图像分析 2002年第2期7卷 77-82,89页

作者： WANG Xiao - mei, SHAN Jun, CHEN Zhuo - huai( Department of Pathology, shenzhen People’s hospital of Guangdong Province, shenzhen 518020, china Department of Radiology, shenzhen People s hospital, shenzhen 518020, china) Department of Pathology Shenzhen People's Hospital of Guangdong ProvinceShenzhen 518020China Department of Radiology Shenzhen People's HospitalShenzhen 518020China

Aim: To investigate glycoconjugate changes on the cell surface of proliferative lesions and neoplasms of mice lungs at various stages of tumorigenesis, the relation between progressive development of mouse pulmonary tumors and expression of cell surface saccharide. Materials and methods: Thirty - one male A/J strain mice at 5 weeks of age were treated intraperitoneally with a single injection of 20 - methylcholanthrene (20 - MC), 292 pulmonary lesions including 31 hyperplasias, 145 alveolar adenomas, 61 papillary adenomas, 55 papillary adenocarcinomas and their combined type were obtained. The binding affinities of cells in normal respiratory epithelia and in proliferative lesions to four peroxidases - conjugated lectins, Maclura pomifera agglutinin (MPA), Arachis hypogea agglutinin (PNA), Ricinus communis agglutinin (RCA), and wheat germ agglutinin (WGA) were examined. Results: Cells of hyperplasia and alveolar adenoma showed fairly strong affinity to all the four lectins. However, part of papillary adenoma cells and greater part of papillary adenocarcinoma cells lost their binding affinity to MPA, PNA, and RCA, but not to WGA. The bindings of MPA, PNA and RNA were detected predominently on the luminal surfaces of benign tumors but not on the luminal surfaces of malignant tumors. WGA might bind to varied types of benign and malignant tumors. Pretreated with neuraminidase, the lesions enhanced the staining intensity for the four lectins, the binding sites of WGA to malignant tumor cells were numerous. A distinct difference in lectin binding affinity between hyperplasia / alveolar adenoma/papillary adenoma and papillary adenocarcinoma was clearly shown( x2 = 46.89, P ＜ 0.01, x2 = 36.77, P ＜ 0.01 and x2 = 52.87, P ＜ 0.01 ) in this experiment. The complex glycoconjugates on the cell surface of malignant and benign lesions during the development of pulmonary tumor were changed,malignant tumor cells differed from the surface of benign tumor cells, the levels of total sia

关键词：肺肿瘤凝血素 20-甲基胆蒽

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