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Novel double-layer Silastic testicular prosthesis with controlled release of testosterone in vitro, and its effects on castrated rats

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Asian Journal of Andrology 2017年第4期19卷 433-438页

作者： Hui-Xing Chen Shi Yang Ye Ning Hai-Hao Shao Meng Ma ru-Hui Tian Yu-Fei Liu Wei-Qiang Gao Zheng Li Wei-Liang Xia School of Biomedical Engineering & Med-X Research Institute Shanghai Jiao Tong University Shanghai 200030 China Department of Andrology Urologic Medical Center Shanghai General Hospital Shanghai Jiae Tong University Shanghai 200080 China Shanghai Human Sperm Bank Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200135 China Controlled Release Laboratory Shanghai Institute of Planned Parenthood Research Shanghai 200030 China

Testicular prostheses have been used to deal with anorchia for nearly 80 years. Here, we evaluated a novel testicular prosthesis that can controllably release hormones to maintain physiological levels of testosterone in vivo for a long time. Silastic testicular prostheses with controlled release of testosterone （STPT） with different dosages of testosterone undecanoate （TU） were prepared and implanted into castrated Sprague-Dawley rats. TU oil was applied by oral administration to a separate group of castrated rats. Castrated untreated and sham-operated groups were used as controls. Serum samples from every group were collected to measure the levels of testosterone （T）, follicle-stimulating hormone and luteinizing hormone （LH）. Maximum intracavernous penile pressure （ICPmax） was recorded. The prostates and seminal vesicles were weighed and subjected to histology, and a terminal dexynucleotidyl transferase-mediated UTP nick end labeling （TUNEL） assay was used to evaluate apoptosis. Our results revealed that the weights of these tissues and the levels of T and LH showed significant statistical differences in the oral administration and TU replacement groups compared with the castrated group （P 〈 0.05）. Compared with the sham-operated group, the ICPmax, histology and TUNEL staining for apoptosis, showed no significant differences in the hormone replacement groups implanted with medium and high doses of STPT. Our results suggested that this new STPT could release TU stably through its double semi-permeable membranes with excellent biocompatibility. The study provides a new approach for testosterone replacement therapy.

关键词： controlled-release preparations hormone replacement therapy hypogonadism prosthesis Silastic testosterone

The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine

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Asian Journal of Andrology 2014年第4期16卷 623-630页

作者： Cheng Xu Ying-Chun Li Hua Yang Yan Long Min-Jian Chen Yu-Feng Qin Yan-Kai Xia Ling Song Ai-Hua Gu Xin-ru Wang State Key Laboratory of Reproductive Medicine Institute of Toxicology Nanjing China Key Laboratory of Modern Toxicology of Ministry of Education School of Public Health Nanjing China Department of Physiology Nanjing Medical University Nanjing China Yangz.hou Center for Disease Control and Prevention Yangzhou China Department of Pharmacology China Pharmaceutical University Nanjing China.

Follicle-stimulating hormone receptor （FSHR）, which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein （FSHR-57aa） as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a（＋）-FSHR-57aa plasmid was constructed and expressed in Escherichia coil strain BL21 StarTM （DE3） and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 （16 weeks） after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.

关键词： follicle-stimulating hormone receptor prokaryotic recombinant expression male contraception vaccine

Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs

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Neuroscience Bulletin 2019年第6期35卷 996-1010页

作者： Yuan Li Xueying Sun Houfu Liu Liang Huang Guofeng Meng Yu Ding Wenji Su Jiaqi Lu Sophie Gong Georg C.Terstappen ru Zhang Wandong Zhang Shanghai Key Laboratory of Signaling and Disease Research Laboratory of Receptor-Based Bio-medicineCollaborative Innovation Center for Brain ScienceSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Platform Technology&Sciences GlaxoSmithKline China R&D CentreShanghai 201203China Neurosciences Therapeutic Area Unit GlaxoSmithKline China R&D CentreShanghai 201203China Human Health Therapeutics Research Centre National Research Council of Canada Faculty of Medicine University of OttawaOttawa K1A0R6Canada

An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous *** many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug ***-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB ***, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 ***2±230 ***2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 ***2 to 4185 ***2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.

关键词： Blood-brain barrier Drug transport Induced pluripotent stem cell Cell differentiation Prediction of in vivo permeability

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图书馆学理论创新实现机制

图书情报工作 2015年第23期59卷 17-22页

作者：侯茹北京物资学院图书馆北京101149

[目的 /意义]图书馆学理论创新研究,对推动图书馆学科发展和图书馆工作实践具有重要意义,对新时期图书馆的转型发展具有重要的支撑作用。[方法 /过程]在简要分析图书馆学理论研究现状的基础上,试图以理论分析和案例总结为主要研究方法,... 详细信息

[目的 /意义]图书馆学理论创新研究,对推动图书馆学科发展和图书馆工作实践具有重要意义,对新时期图书馆的转型发展具有重要的支撑作用。[方法 /过程]在简要分析图书馆学理论研究现状的基础上,试图以理论分析和案例总结为主要研究方法,沿着"着眼点——实现路径——合理性评估"的线索提出图书馆学理论创新实现机制的框架。[结果 /结论]以继往开来、善于借鉴和面向现实问题为理论创新着眼点,以总体性、学科体制超越性和批判性知识生产模式为实现路径,以合规律性、合目的性和合规范性为评价标准,提出图书馆学理论创新的实现机制。

关键词：图书馆学理论创新总体性学科体制批判性合理性

身体·主体·社会:20世纪90年代以来欧美经典科幻电影的“赛博格”想象

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上海交通大学学报（哲学社会科学版） 2020年第3期28卷 46-54页

作者：潘汝浙江传媒学院文学院杭州310018

"赛博格"生发于20世纪40年代控制论的土壤,至90年代,演变成乌托邦式的意识形态。而20世纪90年代以来的欧美经典"赛博格"科幻电影,以影像的方式批判因身体差异所导致的伦理秩序的失衡,传达主体自我在数据时代被解构所带来的迷惘情绪,揭... 详细信息

"赛博格"生发于20世纪40年代控制论的土壤,至90年代,演变成乌托邦式的意识形态。而20世纪90年代以来的欧美经典"赛博格"科幻电影,以影像的方式批判因身体差异所导致的伦理秩序的失衡,传达主体自我在数据时代被解构所带来的迷惘情绪,揭示为控制论所定义的赛博空间的"专制"特征;进而对"身体"的进化与虚化、跨越差异性的新主体自我的重构、"民主"式乌托邦赛博空间展开想象,突破了人与非人、意识与模拟等二元对立的藩篱,表达了对新技术条件下人类生存状态的忧思与展望。

关键词：电影科幻电影赛博格

Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma

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Chinese Journal of Cancer 2015年第11期34卷 514-521页

作者： Li-Ling Luo Lei Zhao Mian Xi Li-ru He Jing-Xian Shen Qiao-Qiao Li Shi-Liang Liu Peng Zhang Dan Xie Meng-Zhong Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Department of Radiation Oncology Sun Yat-sen University Cancer Center Collaborative Innovation Center for Cancer Medicine Medical Imaging and Interventional Center Sun Yat-sen University Cancer Center

Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ***: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards ***: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.

关键词： Esophageal squamous cell carcinoma Insulin-like growth factor-binding protein-3 Immunohistochemistry Radiotherapy response Prognosis

Electrochemical capacitance-voltage characterization of plasma-doped ultra-shallow junctions

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Frontiers of Electrical and Electronic Engineering in China 2008年第1期3卷 116-119页

作者： Huizhen WU Guoping ru Yonggang ZHANG Chengguo JIN Bunji MIZUNO Yulong JIANG Xinping QU Bingzong LI Department of Microelectronics Fudan UniversityShanghai 200433China State Key Laboratory of Functional Materials for Informatics Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200050China Ultimate Junction Technologies Inc. 3-1-1YagumonakamachiMoriguchiOsaka 570-8501Japan

Ultra-shallow Si p^(+)n junctions formed by plasma doping are characterized by electrochemical capacitance-voltage(ECV).By comparing ECV results with those of secondary ion mass spectroscopy(SIMS),it is found that the dopant concentration profiles in heavily-doped p+layer as well as junction depths measured by ECV are in good agreement with those measured by ***,the ECV measurement of dopant concentration in the underlying lightly doped n-type substrate is significantly influenced by the upper heavily-doped *** ECV technique is also easy to control and *** ECV results of ultra-shallow junctions(USJ)formed by plasma doping followed by different annealing processes show that ECV is capable of reliably characterizing a Si USJ with junction depth as low as 10 nm,and dopant concentration up to 10^(21) cm^(-3).Also,its depth resolution can be as fine as 1 ***,it shows great potential in application for characterizing USJ in the sub-65 nm technology node CMOS devices.

关键词： electrochemical capacitance-voltage ultrashallow junction dopant concentration

Original article： Perichondrium/cartilage composite graft for repairing large tympanic membrane perforations and hearing improvement

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Chinese Medical Journal 2010年第3期 301-304页

作者： CHEN Xiao-wei YANG Hua GAO ru-zhen YU Rong GAO Zhi-qiang Department of Otolaryngology-Head and Neck Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100730 China

Background The main risk factors for postoperative failure in tympanoplasties are large perforations that are difficult to repair, annular perforations, and a tympanic membrane （TM） with extensive granular myringitis that require middle ear exploration and mastoidectomy. The aim of this study was to investigate a novel technique of perichondrium/cartilage composite graft for repairing the large TM perforation in the patient of otitis media. Methods Retrospective chart reviews were conducted for 102 patients with large tympanic membrane perforations, who had undergone tympanoplasty from August 2005 to August 2008. Tympanoplasty or tympanomastoidectomy using a perichondrium/cartilage composite graft was analyzed. The tragal or conchal perichondrium/cartilage was used to replace the tympanic membrane in patients. Results Patients aged from 13 to 67 years were followed up in average for 24 months （10-36 months）. Seventy-four ears （72.61%） were used the tragal perichondrium/cartilage as graft material and 27 ears （27.39%） were used the conchal perichondrium/cartilage. Graft take was successful in all patients. Postoperative complications such as wound infection, hematoma, or sensorineural hearing loss were not identified. Nine patients （8.82%） had the partial ossicular replacement prosthesis, 14 patients （13.72%） using the autologous curved incus and 79 patients （77.45%） without prosthesis. Successful closure occurred in 92% of the ears. A total of 85.8% patients achieved a postoperative hearing improvement. Conclusions The graft underlay tympanoplasty using perichondrium/cartilage composite is effective for the majority of patients with large perforation. The hearing was improved even if the mastoidectomy was required in the patients with otitis media with extensive granulation.

关键词： otitis media perichondrium/cartilage tympanoplasty tympanomastoidectomy hearing improvement

Differential expression of microRNAs in aortic tissue and plasma in patients with acute aortic dissection

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Journal of Geriatric Cardiology 2015年第6期12卷 655-661页

作者： Xiao-Jian WANG Bi HUANG Yan-Min YANG Liang ZHANG Wen-Jun SU Li TIAN Tian-Yi LU Shu ZHANG Xiao-Han FAN ru-Tai HUI State Key Laboratory of Cardiovascular Disease Sino-German Laboratory for Molecular Medicine Fuwai Hospital National Center for CardiovascularDiseases Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China State Key Laboratory of Cardiovascular Disease Department of Cardiology Fuwai Hospital National Center for Cardiovascular Diseases Chinese Acad-emy of Medical Sciences & Peking Union Medical College Beijing China State Key Laboratory of Cardiovascular Disease Department of Cardiovascular Surgery Fuwai Hospital National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Background Biomarker-assisted diagnosis of acute aortic dissection （AAD） is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study is to search for new potentially microRNA （miRNAs） biomarkers in AAD. Methods The miRNAs expression profiles in ascending aortic tissue and plasma were examined by microarray analysis in two sets or groups. The tissue group was composed of four patients with AAD and four controls of healthy male organ donors. The plasma group included 20 patients with AAD and 20 controls without cardiovascular disease. Bioinformatics was used to analyze the poten- tial targets of the differentially expressed miRNAs. Results Our study revealed that in AAD patients, the aortic tissue had 30 differentially expressed miRNAs with 13 up-regulated and 17 down-regulated, and plasma had 93 differentially expressed miRNAs, of which 33 were up-regulated and 60 were down-regulated. Four miRNAs were found to be up-regulated in both aortic tissue and plasma in AAD patients. The predicted miRNA targets indicated the four dysregulated miRNAs mainly targeted genes that were associated with cell-cell adhesion, extracellular matrix metabolism, cytoskeleton organization, inflammation, and multiple signaling pathways related to cellular cycles. Con- clusions Four miRNAs, which are up-regulated both in aortic tissue and in plasma in AAD patients, have been identified in this study. These miRNAs might be potential diagnostic biomarkers for AAD. Larger sample investigations are needed for further verification.

关键词： Acute aortic dissection Biomarker Diagnosis MicroRNAs