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One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C

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World Journal of Clinical Cases 2022年第28期10卷 10085-10096页

作者： Jing-Hang Xu Sa Wang Da-Zhi Zhang Yan-Yan Yu Chong-Wen Si Zheng Zeng Zhong-Nan Xu Jun Li Qing Mao Hong Tang Ji-Fang Sheng Xin-Yue Chen Qin Ning Guang-Feng Shi Qing Xie Xi-Quan Zhang Jun Dai department of Infectious Diseases Center for Liver DiseasesPeking University First HospitalBeijing 100094China Clinical and Research Center of Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China department of Infectious Diseases The Second Affiliated Hospital with Chongqing Medical UniversityChongqing 400010China Jiangsu Chia-tai Tianqing Pharmaceutical Co. LtdNanjing 222006Jiangsu ProvinceChina department of Infectious Diseases The First Affiliated Hospital with Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina department of Infectious Diseases Southwest China HospitalChongqing 400038China department of Infectious Diseases West China HospitalChengdu 610041Sichuan ProvinceChina department of Infectious Diseases The First Affiliated Hospital of Zhejiang UniversityHangzhou 310010Zhejiang ProvinceChina department of International Medicine Beijing Youan HospitalCapital Medical UniversityBeijing 100069China department and Institute of Infectious Diseases Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina department of Infectious Diseases Huashan HospitalFudan UniversityShanghai 200040China department of Infectious Diseases Ruijin HospitalJiaotong University School of MedicineShanghai 200025China

BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV(Baraclude)when used in Chinese patients with chronic hepatitis B(CHB)in phase III clinical trials(Clinical *** number,NCT-01926288)at weeks 48,96,and *** To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or *** In this double-blind study,we randomly assigned patients to receive 0.5 mg/d ETV(Group A)or ETV maleate(Group B)(ratio,1:1),each with a placebo tablet for 48 ***,all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week *** primary efficacy endpoint was the reduction in HBV DNA levels from *** endpoints included the proportion of patients with undetectable HBV DNA(0.05),viral suppression with HBV DNA0.05)and HBe Ag seroconversion(28.77%vs 20.00%,P>0.05)occurred similarly between Groups A and B at week ***,there was a significant difference in the proportion of patients with normal ALT levels(91.14%vs 78.38%,P0.05),percentages of patients who achieved undetectable HBV DNA(100%vs 100%,P>0.05)and rates of ALT normal

关键词： Chronic hepatitis B Entecavir maleate Randomized controlled trial Treatment outcome Mutation Genotype

Up-regulation of Niacinamide in Intervertebral Disc Aggrecan in vitro

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Journal of huazhong university of science and technology(medical sciences) 2006年第1期26卷 89-92页

作者：熊晓芊杨述华邵增务刘心詹子睿段德宇 department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

The regulatory effects of niacinamide （Nia） on intervertebral disc （IVD） aggrecan in vitro was investigated. Chiba＇s 10 ng/mL interleukin-1 （IL-1）-induced rabbit IVD degeneration model in vitro was established. 0.5, 0. 25 and 0.05 mg/mL Nia was added to normal and degenerated IVDs for intervention. On the first and second week after intervention, safranin O-fast green staining intensity and glycosaminoglycan （GS） content were measured. The expression of aggrecan core protein was detected by RT-PCR. The results showed：（1） After treatment with 0. 5 mg/mL Nia for one week, the GS content in nucleus pulposus （NP） was increased by 44.80% as compared with control group （P〈0. 01） ; The GS content in IL-1 induction groups was increased with the increase of Nia concentrations： After treatment with 0. 5 mg/mL for one week, the GS content in NP was increased by 68.30% as compared with control group （P〈0. 01）. After two weeks, GS content in NP and fibrous rings was still higher than in control group at the same period （P〈0. 01） and untreated group （P〈0.01）. （2） Safranin O-fast green staining revealed that with the increase of Nia concentrations, staining density in NP and fibrous rings was increased and histological structure damage to IVDs by IL-1β was alleviated. （3） RT-PCR showed that the expression of core protein gene in IL-1β-induced degenerated IVDS was increased with the increase of Nia concentrations. It was concluded that under conditions in vitro, Nia could up-regulate the expression of aggrecan in IVDs and protect IVDs from IL-1β-induced degeneration at least partially, which offers a potential choice for IVD degeneration clinical therapy.

关键词： intervertebral disc degeneration niacinamide interleukin-1

Expression of Telomerase Subunits in Gastric Cancer

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Journal of huazhong university of science and technology(medical sciences) 2005年第6期25卷 741-743页

作者：陈凤花胡丽华李一荣王琳 Laboratory department of Union hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

To detect the expression of telomerase subunits （human telomerase reverse transcriptase, human telomerase associated protein 1 and human telomerase RNA） in gastric cancer and to examine the role that different telomerase subunits play in the gastric carcinogenesis, reverse transcription-polymerase chain reaction （RT-PCR） was used to detect telomerase suhunits messenger RNA in 24 samples of gastric cancer and corresponding non-cancerous tissue. The results showed that the positive rate of hTERT mRNA from gastric cancer and corresponding non-cancerous tissues was 100% and 25 %, respectively. The former was significantly higher than the latter （X^2 = 26.4, P〈0.01）. The positive rate of hTEP1 mRNA from gastric cancer and corresponding non-cancerous tissues was 100 % and 91.7%, respectively and no significant difference was found between them （X^2 =2.1, P〉0.05）. The positive rates of hTR for gastric cancer and corresponding non-cancerous tissues were both 100 % and no significant difference existed between them. It is concluded that in contrast to hTEP1 and hTR, the up-regulation of hTERT mRNA expression may play a more important role in the development of gastric cancer.

关键词： gastric cancer, human telomerase reverse transcriptase (hTERT) human telomerase associated protein 1 (hTEP1) human telomerase RNA (hTR)

Construction of competency evaluation measures for operating room nurses

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Chinese Nursing Research 2016年第4期3卷 181-184页

作者： Yu-Mei Wang Li-Juan Xiong Yi Ma Xing-Lian Gao Wen-Fang Fu Geriatric department Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Nursing department Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Wuhan university WuhanHubei 430079China department of Operating Zoom Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Nursing department Central Hospital of JingzhouJingzhouHubei 434020China

Objective： To develop a scientific and reasonable competency evaluation index system for operating room nurses （ORN） in order to provide a tool for selecting, training and evaluating operating room nurses in China. Methods： A multiple-method approach including in-depth interviews and the Delphi and Analytic Hi- erarchy Process （AHP） was used. Eighteen interviews were undertaken to explore the components of ORN competencies, and then 30 operating room experts were consulted to gain consensus. Finally, the AHP was adopted to determine the relative weights of competency elements, thus increasing the ac- curacy of the results. Results： Results of the interviews suggested that there were 32 items of ORN core competency. Results of the DHP （Delphi and AHP） revealed 22 ORN core competencies in four dimensions, such as specialized knowledge, professional ability, personality and self-motivation. The weights of these four dimensions were 0.477, 0.138, 0.256, and 0.128, respectively. Condu.~ions： The construction of an ORN core competency evaluation index system in this study con- tained not only explicit competence but also implicit competence, which reflected the requirements for operating room nurses comprehensively in China. In particular, as the system presented the specialized features of an operating room, it would be of great importance for both nurses and hospitals.

关键词： CompetencyOperating roomNursesNursingDelphiEvaluation measure

Binding of Divalent H-2K^(d)/IgG2aFc Fusion Protein to Murine Macrophage via Fc-FcR Interaction

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Cellular & Molecular Immunology 2007年第2期4卷 147-151页

作者： Wei Xiao Xueling Chen Lin Zhou Shengjun Lu Zhihui Liang Xiongwen Wu department of Immunology Tongji Medical College Huazhong University of Science ＆ Technology Wuhan 430030 China department of Immunology School of Medicine Shihezi University Shihezi 832002 China

Peptide-MHC class I complex （pMHC） is a specific ligand for TCR recognition, and important for CD8^＋T cell activation. Here we described a genetically engineered divalent class I major histocompatibility complex （MHC） molecule, H-2K^d/IgG2aFc, a fusion protein consisting of the extracellular domains of H-2K^d, a murine MHC class I molecule, and the Fc region of IgG2a. This fusion protein is expected to attach the H-2K^d molecule to the surface of murine macrophage （MФ） through its Fc portion binding to Fc receptor （FcR） of MФ. cDNAs coding for the extracellular domains of H-2K^d and the Fc region of IgG2a were cloned respectively, and then recombined into plasmid pcDNA3.1（＋）. The H-2K^d/IgG2aFc protein was expressed by the plasmid-transfected cell line J558L, and purified from its supernatant with a Staphylococcal Protein A （SPA） column. The fusion protein showed a 58.4 kDa band as revealed by SDS-PAGE and Western blotting with murine IgG-specific antibody, which consists with that expected for extracellular domains of H-2K^d heavy chain plus the Fc region of IgG2a. The sandwich ELISA assay with antibodies specific for Fc portion and for H-2K^d indicated the fusion protein consists of both Fc portion and H-2K^d. Peritoneal MФ of C57BL/6 （H-2K^b） can be stained with H-2K^d specific monoclonal antibody （mAb） after incubated with the H-2K^d/IgG2aFc fusion protein. These results demonstrate the fusion protein can be used to attach the H-2K^d molecule to the surface of murine MФ, and provides a novel means to manipulate the T cell recognized epitope on the surface of murine MФ, which can be applied to activate antigen-specific cytotoxic T lymphocyte （CTL）.

关键词： H-2K^d/IgG2aFc divalent MHC fusion protein Fc receptor

E Sequence Analysis of Persistently Infected Mutant Japanese Encephalitis Virus Strains

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Journal of huazhong university of science and technology(medical sciences) 2006年第4期26卷 408-410页

作者：李琪徐可树王华枫周霞 department of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Summary： A persistent infection model was established after human hepatoma cells infected by Japanese encephalitis viruses were subcultured for several times. Viral titers of mutant viruses in persistently infected cells were examined by plaque methods using BHK cells. Nucleotides of the E coding region of two wild and two mutant viruses were amplified by RT-PCR. PCR products were sequenced by ABI-PRSM^TM310 sequencing system. Compared to JaGAr-01 wild strains, four amino acids were replaced （E61Tyr→Asp, E219His→Tyr, E384Val→Glu, E418Pro→Ala） in the E sequence of JaGAr-01 persistently-infected mutant strains. Eleven amino acid replacement （E51Arg →Ser, E61Tyr→Asp, E83Lys→Glu, E123Ser→Arg, E209Arg→Lys, E227Pro→Ser, E276Asp→er, E290Arg→Lys, E387Lys→Arg, E418Leu→Pro, E454Arg→Gly） was also noted when we compared the E sequence between persistently infected Nakayama and its wild strains. A lot of similarities of amino acid sequence between mutant strains JaGAr-01 and Nakayama were also noted. It was concluded that geno-variation existed in E region of mutant viruses and the mutant protein encoded by E region, especially the mutation of E61 （Tyr→Asp） may contribute to the maintenance of the persistent infection of Japanese encephalitis virus.

关键词： Japanese encephalitis virus persistent infection E sequence analysis geno-variation

Changes of Expression of Stretch-activated Potassium Channel TREK-1 mRNA and Protein in Hypertrophic Myocardium

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Journal of huazhong university of science and technology(medical sciences) 2006年第1期26卷 31-33页

作者：程龙献苏方成瑞奔曾哥樊红黄恺王敏彭红玉梅春丽赵芳廖玉华 department of Cardiology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

The expression of stretch activated potassium channel TREK-1 mRNA and protein of hypertrophic myocardium was measured. Using a model of hypertrophy induced by coarctation of abdominal aorta in male Wistar rats, the expression of TREK-1 mRNA and protein was detected by using semi quantitative RT-PCR and Western blot respectively. At 4th and 8th week after constriction of the abdominal aorta , rats developed significant left ventricular hypertrophy. As compared to sham-operated group, stretch-activated potassium channel TREK-1 mRNA was strongly expressed and protein was up regulated in operation groups （P〈0.05）. It was concluded that the expression of TREK-1 was up-regulated in hypertrophic myocardium induced by chronic pressure overload in Wistar rats.

关键词： hypertrophic myocardium stretch-activated potassium channel ventricular remodeling electrical remodeling

Propofol Target-Controlled Infusion Modeling in Rabbits:Pharmacokinetic and Pharmacodynamic Analysis

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Journal of huazhong university of science and technology(medical sciences) 2016年第3期36卷 428-433页

作者：陈建颜易明姚尚龙张雪萍 department of Anesthesiology Shenzhen Baoan Hospital Affiliated to Southern Medical UniversityShenzhen 518100China department of Anesthesiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China department of Anesthesiology Shenzhen People's HospitalShenzhen 518020China

This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.

关键词： propofol target-controlled infusion modeling rabbit pharmacokinetics pharmacodynamics anesthetic depth

A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3070-3086页

作者： Chao Zhang Qiang Guo Lifeng Chen Zheming Wu Xiao-Jian Yan Chengyang Zou Qiuxue Zhang Jiahong Tan Tian Fang Qunxian Rao Yang Li Shizhen Shen Min Deng Liewei Wang Huanyao Gao Jia Yu Hu Li Cheng Zhang Somaira Nowsheen Jake Kloeber Fei Zhao Ping Yin Chunbo Teng Zhongqiu Lin Kun Song Shuzhong Yao Liangqing Yao Lingying Wu Yong Zhang Xiaodong Cheng Qinglei Gao Jian Yuan Zhenkun Lou Jin-San Zhang Beijing Institute of Basic medical sciences 100850BeijingChina department of Oncology Mayo ClinicRochesterMN55905USA School of Pharmaceutical sciences Wenzhou Medical University325035WenzhouZhejiangChina Key Laboratory of Endocrine Gland Diseases of Zhejiang Province Zhejiang Provincial People’s Hospital310014HangzhouZhejiangChina department of Gynecology Zhejiang Provincial People’s Hospital310014HangzhouZhejiangChina department of Gynecology the First Affiliated Hospital of Wenzhou Medical University325000WenzhouZhejiangChina Wuhan Kingwise Biotechnology Co. Ltd.430206WuhanHubeiChina Cancer Biology Research Center(Key Laboratory of the Ministry of Education) Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030WuhanHubeiChina department of Gynecological Oncology Sun Yat-sen Memorial HospitalSun Yat-sen University510120GuangzhouGuangdongChina Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for Reproductive Health Research 310006HangzhouZhejiangChina Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases 310006HangzhouZhejiangChina department of Molecular Pharmacology and Experimental Therapeutics Mayo ClinicRochesterMN55905USA department of Dermatology University of California San DiegoSan DiegoCA92122USA Key Laboratory of Saline-alkali Vegetation Ecology Restoration Ministry of EducationCollege of Life ScienceNortheast Forestry University150040HarbinChina Division of Gynecology Oncology Department of Obstetrics and GynecologyQilu HospitalShandong University250012JinanShandongChina department of Obstetrics and Gynecology the First Affiliated HospitalSun Yat-Sen University510080GuangzhouGuangdongChina department of Gynecologic Oncology Obstetrics and Gynecology Hospital of Fudan University200090ShanghaiChina department of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of

Poly(ADP-ribose)polymerase(PARP)inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination(HR)***,many patients without apparent HR defects also respond well to PARP inhibitors/*** biomarker responsible for this mechanism remains ***,we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient *** inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage(ATM)signaling-induced pro-apoptotic ribosomal stress,which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA ***,the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/*** gene panel as an independent biomarker was validated by multiple published clinical datasets,as well as by an ovarian cancer organoids library we *** importantly,its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS ***,we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell *** drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired ***,our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.

关键词： drugs BRCA panel