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Toxicological effects of PBDEs on carassius aurats

Chinese Journal Of Geochemistry 2010年第2期29卷 217-222页

作者： H.AN Zhaoxlang lv chunxia ZHENG Zengren School of Chemical Engineering Huaihai Institute of Technology Jiangsu Lianyungang 222005 China Jiaonan Agricultural Bureau Shandong Qingdao 266400 China Animal Quarantine Section Agricultural Ministry Shandong Qingdao 266033 China

In this study the effects of polybrominated diphenyl ether compounds (PBDEs), BDE-47 and BDE-99 on carassius aurats were discussed. The reproductive capacity viability and proliferation percent decreased with in-creasing BDE-47and BDE-99 concentrations (p<0.05), presenting a dose-dependent manner. Physiological bio-markers such as cholesterol (CHL), acetylcholinesterase (AChE), ethoxyresorufin-O-deethylase (EROD) and vitamin were studied to reveal the toxicological effects of BDE-47 and BDE-99 exposure. CHL levels generally decrease with increasing BDE-47 exposure. However, there were no significant differences between the samples and the con-trol. As to BDE-99, the CHL level decreased as compared with the control level when the BDE-99 concentrations reached 20 μg/L (p<0.05). The degree of inhibition of the AChE increased with the increase of DE-47and BDE-99 concentrations. The EROD activity during 72 hours' exposure significantly increased to 20 μg/L for BDE-47 (p<0.05), however, EROD activity was not significantly different at different concentrations of BDE-99 (p<0.05). Carassius aurats hepatocytes reacted to the BDE-47 exposure with increasing EROD activities in the dose depend-ent manner. Although at lower concentrations, the induced effects of BDE-47 and BDE-99 were not significantly different, though BDE-47 showed strong induced effects on the EROD activity with increasing concentrations in carassius aurats hepatocytes. In contrast, BDE-99 did not influence EROD activity consistently. The VA level of carassius aurats was significantly different from that of the controls for BDE-99 (p<0.001), as far as the VA level was significantly lower of carassius aurats than the controls for BDE-47 (p<0.001). CHL, AChE, EROD, and VA levels in carassius aurats were differently affected by BDE-47 and BDE-99 exposures, therefore, they would be good indicators for exposure.

关键词： PBDEs 鲫鱼毒性

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多西他赛联合顺铂与伊立替康联合顺铂治疗晚期NSCLC的疗效

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现代肿瘤医学 2016年第24期24卷 3947-3950页

作者：吕春霞汉阴县人民医院内一科陕西汉阴725100

目的:观察多西他赛联合顺铂方案(DP方案)与伊立替康联合顺铂方案(IP方案)一线治疗晚期非小细胞肺癌(NSCLC)的近期疗效和不良反应。方法:采用前瞻性随机对照的临床研究设计,将65例经组织学或细胞学确诊的初治晚期NSCLC患者分为DP方案组... 详细信息

目的:观察多西他赛联合顺铂方案(DP方案)与伊立替康联合顺铂方案(IP方案)一线治疗晚期非小细胞肺癌(NSCLC)的近期疗效和不良反应。方法:采用前瞻性随机对照的临床研究设计,将65例经组织学或细胞学确诊的初治晚期NSCLC患者分为DP方案组和IP方案组,观察其近期有效率(RR)、疾病控制率(DCR)、疾病进展时间(TTP)、中位生存时间(MST)、1年生存率和不良反应。结果:DP方案组中,部分缓解(PR)11例,疾病稳定(SD)14例,疾病进展(PD)7例,RR为34.4%(11/32),DCR为78.1%(25/32);TTP为7.5个月,MST为12.5个月,1年生存率为53.1%(17/32)。IP方案组中,PR 10例,SD 15例,PD 8例,RR为30.3%(10/33),DCR为75.8%(25/33),TTP为6.9个月,MST为11.8个月,1年生存率为54.5%(18/33),上述临床疗效及生存期的比较,均无统计学差异(P>0.05)。两组患者的主要不良反应为血液学毒性、消化道反应和脱发,上述不良反应有统计学差异(P<0.05)。IP方案组腹泻的发生率高于DP方案组(P<0.05),而DP方案组粒细胞减少发生率高于IP方案组(P<0.05)。结论:DP方案和IP方案治疗晚期NSCLC疗效确切,不良反应均可耐受。

关键词：非小细胞肺癌多西他赛伊立替康顺铂

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大学生入党的影响因素分析——以川渝高校为例

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四川理工学院学报（社会科学版） 2014年第2期29卷 91-99页

作者：赵凯叶文明吕春霞四川理工学院经济与管理学院四川自贡643000

当代大学生,特别是学生党员将成为党和国家的中流砥柱,但当前大学生党员的人生观、价值观和入党动机呈现出多元化趋势,与主流有偏差。为此,需要明确大学生入党的影响因素及影响权重,便于改进学生党建工作。从收集大学生入党的影响因素出... 详细信息

当代大学生,特别是学生党员将成为党和国家的中流砥柱,但当前大学生党员的人生观、价值观和入党动机呈现出多元化趋势,与主流有偏差。为此,需要明确大学生入党的影响因素及影响权重,便于改进学生党建工作。从收集大学生入党的影响因素出发,归纳出16条研究项目,用SPSS数据统计软件对调查数据进行探索性因素分析和主成份因素分析,抽取出党组织培养与管理、家庭期望、借鉴因素和成长环境四个影响力最大的主成份因素。并由此探索其指导意义,首先应立足于其大学生活,从党校教学内容和管理、学生支部的建设、完善两课教育三个平台入手,创新党组织培养与管理;其次把其它几个主成份因素统筹于大学生党员成长、成才的教育中,为培养高素质学生党员营造有利条件。

关键词：大学生党员思想政治教育高校党建党校教学学生支部两课教育

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An Improved Hybrid Collaborative Filtering Algorithm Based on Tags and Time Factor

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Big Data Mining and Analytics 2018年第2期1卷 128-136页

作者： chunxia Zhang Ming Yang Jing lv Wanqi Yang the School of Computer Science and Technology Nanjing Normal University

The Collaborative Filtering(CF) recommendation algorithm, one of the most popular algorithms in Recommendation Systems(RS), mainly includes memory-based and model-based methods. When performing rating prediction using a memory-based method, the approach used to measure the similarity between users or items can significantly influence the recommendation performance. Traditional CFs suffer from data sparsity when making recommendations based on a rating matrix, and cannot effectively capture changes in user interest. In this paper, we propose an improved hybrid collaborative filtering algorithm based on tags and a time factor(TTHybridCF), which fully utilizes tag information that characterizes users and items. This algorithm utilizes both tag and rating information to calculate the similarity between users or items. In addition, we introduce a time weighting factor to measure user interest, which changes over time. Our experimental results show that our method alleviates the sparsity problem and demonstrates promising prediction accuracy.

关键词： recommendation system similarity tag time factor

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A Novel Human Antibody,HF,against HER2/erb-B2 Obtained by a Computer-Aided Antibody Design Method

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Engineering 2021年第11期7卷 1566-1576页

作者： chunxia Qiao Ming lv Xinying Li Xiaoling Lang Shouqin lv Mian Long Yan Li Shusheng Geng Zhou Lin Beifen Shen Jiannan Feng State Key Laboratory of Toxicology and Medical Countermeasures Institute of Pharmacology and ToxicologyBeijing 100850China Beijing Key Laboratory of Therapeutic Gene Engineering Antibody Beijing 100850China Institute of Military Cognitive and Brain Sciences Beijing 100850China Beijing Mabworks Biotech Co.Ltd. Beijing 100176China Institute of Mechanics Chinese Academy of SciencesBeijing 100190China

Fully human antibodies have minimal immunogenicity and safety *** present,most potential antibody drugs in clinical trials are humanized or fully *** antibodies are mostly generated using the phage display method(in vitro)or by transgenic mice(in vivo);other methods include B lymphocyte immortalization,human–human hybridoma,and single-cell polymerase chain ***,we describe a structure-based computer-aided de novo design technology for human antibody *** on the complex structure of human epidermal growth factor receptor 2(HER2)/Herceptin,we first designed six short peptides targeting the potential epitope of HER2 recognized by ***,these peptides were set as complementarity determining regions in a suitable immunoglobulin frame,giving birth to a novel anti-HER2 antibody named "HF,"which possessed higher affinity and more effective anti-tumor activity than *** work offers a useful tool for the quick design and selection of novel human antibodies for basic mechanical research as well as for imaging and clinical applications in immune-related diseases,such as cancer and infectious diseases.

关键词： HER2/erb-B2 Human antibody Computer-aided design

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Selection and characterization of the novel anti-human PD-1 FV78 antibody from a targeted epitope mammalian cell-displayed antibody library

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Cellular & Molecular Immunology 2018年第2期15卷 146-157页

作者： Longlong Luo Shi Wang Xiaoling Lang Tingting Zhou Jing Geng Xinying Li chunxia Qiao Jiannan Feng Beifen Shen Ming lv Yan Li Laboratory of Immunology Institute of Basic Medical SciencesBeijing100850China Laboratory of Cellular and Molecular Immunology Institute of ImmunologyHenan UniversityKaifeng475001China

Currently,display-based methods are well established and widely used in antibody engineering for affinity maturation and structural stability *** obtained a novel anti-human programmed death 1(PD-1)antibody using computer-aided design and a mammalian cell display technology *** used computer-aided modeling and distance geometry methods to predict and assign the key residues that contributed to the binding of human PD-L1 to ***,we analyzed the sequence of nivolumab(an anti-human PD-1 antibody,referred to as MIL75 in the article)to determine the template for antibody design and library *** identified a series of potential substitutions on the obtained template and constructed a virtual epitope-targeted antibody library based on the physicochemical properties and each possible location of the assigned key *** virtual antibody libraries were displayed on the surface of mammalian cells as the antigen-binding fragments of full-length immunoglobulin ***,we used flow cytometry and sequencing approaches to sort and screen the ***,we obtained a novel anti-human PD-1 antibody named ***78 competitively recognized the PD-1 epitopes that interacted with MIL75 and possessed an affinity comparable to *** results implied that FV78 possessed equivalent bioactivity in vitro and in vivo compared with MIL75,which highlighted the probability and prospect of FV78 becoming a new potential antibody therapy.

关键词： antibody computer-guided modeling distance geometry human PD-1 mammalian cell-displayed antibody library

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Synthesis of Fucosylated Chondroitin Sulfate tetrasaccharide derivative

Synthesis of Fucosylated Chondroitin Sulfate tetrasaccharide...

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中国化学会第三届全国糖化学会议

作者： Changlun lv Haijiao Chen chunxia Li Key Laboratory of Marine Drugs Ministry of EducationKey Laboratory of Glycoscience and GlycotechnologyShandong ProvinceSchool of Medicine and PharmacyOcean University of China Qingdao

Fucosylated chondroitin sulfate,a unique glycosaminoglycan isolated from the wall of sea cucumber,is mainly composed of N-acetylgalactosamine,D-glucuronic acid,L-fucose and ***,N-acetylgalactosamine and fucose are linked to glucuronic acid by β 1→4 and α1→3 glycosidic bonds,*** studies have shown that FCS has potential medicinal application with various pharmacological effects such as anti-coagulation,anti-tumor,anti-virus,promoting nerve axon growth and regulating immune and cell *** to the complex structure of FCS,it is difficult to isolate the oligosaccharides with uniform structure confirmation,which limits the in-depth study of the mechanism and structure-activity relationship of FCS.A series of FCS oligosaccharide derivatives were designed and synthesized,and a unique FCS tetrasaccharide derivative（Scheme 1） was synthesized for the first *** efficient synthesis strategy was established,which afforded FCS oligosaccharides derivatives for biological evaluation.

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H_(2)O_(2)-responsive multifunctional nanocomposite for the inhibition of amyloid-βand Tau aggregation in Alzheimer's disease

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BMEMat(BioMedical Engineering Materials) 2023年第1期1卷 91-99页

作者： Luying Qiao Yang Shen Shiyu Zhang Man Wang Guanglei lv Qingqing Dou chunxia Li Institute of Molecular Sciences and Engineering Institute of Frontier and Interdisciplinarity ScienceShandong UniversityQingdaoChina School of Environmental Science and Engineering Shandong UniversityQingdaoChina Center for Biotechnology and Biomedical Engineering Yiwu Research Institute of Fudan UniversityYiwuChina Institute of Material Research&Engineering Agency for ScienceTechnology and Research(A^(*)STAR)SingaporeSingapore

Amyloid-β(Aβ)and Tau proteins are the main components of Aβplaques and neurofibrillary tangles in Alzheimer's disease(AD),and their abnormal ag-gregation is closely related to the pathogenesis of *** production of reactive oxygen species(ROS)and the aggregation of Aβand Tau form a vi-cious circle,which leads to the aggravation of ***,inhibiting the aggregation of Aβand Tau or scavenging ROS is not able to effectively reverse the progression of ***,we prepared a H_(2)O_(2) responsive multifunctional nanocomposite UCNPs@mSiO_(2)-MB@AuNPs(abbreviated as USMA)to inhibit the aggregation of Aβand *** this system,USMA could respond to H_(2)O_(2) to detach gold nanoparticles(AuNPs)and lead to the release of meth-ylene blue(MB)from mesoporous silica(mSiO_(2)),where AuNPs and MB can inhibit Aβand Tau aggregation,***,USMA could consume H_(2)O_(2) by reacting with ***,upconversion lumines-cence of UCNPs can be used to track USMA and monitor MB release,which could provide information on the content of MB in the lesion ***-tantly,the USMA can effectively reduce the cytotoxicity induced by Aβand Tau *** work opens up a possibility to improve therapeutic ef-ficacy for the treatment of AD.

关键词： Alzheimer's disease Amyloid-β Tau upconversion nanoparticles

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Potent anti-angiogenesis and anti-tumor activity of a nove human anti-VEGF antibody, MIL60

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Cellular & Molecular Immunology 2014年第3期11卷 285-293页

作者： Jing Yang Qun Wang chunxia Qiao Zhou Lin Xinying Li Yifei Huang Tingting Zhou Yan Li Beifen Shen Ming lv Jiannan Feng Laboratory of Immunology Institute of Basic Medical Sciences Beijing China Department of Pathogens and Immunology Logistics College of Chinese People's Armed Police Forces Tianjin China Department of Ophthalmology General Hospital of People's Liberation Army Beijing China These authors contributed equally to this work

Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor （VEGF） has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEGF can starve tumors. Avastin, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. However, the price of Avastin is extremely high for Chinese people. Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin （the KD value of MIL60 was 44.5 pM, while that of Avastin was 42.7 pM）. MIL60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation （the IC5o value of M IL60 was 31-6.4 ng/ml and that of Avastin was 47--.8.1 ng/ml）, migration （8 pg/ml or 0.8 pg/ml MIL60 versusthe control： P〈O.05） and tube formation （2 I^g/ml or 0.2 lzg/ml MIL60 versusthe control： P〈O.05） viathe VEGFR2 signaling pathway. Moreover, MIL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistry analysis （MIL60 versus N.S.： P=0.0007; Avastin versus N.S.： P=0.00046）. These data suggest that MIL60 is a potential therapeutic, anti-angiogenic agent. Our work provides a novel anti-VEGF antibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.

关键词： angiogenesis anti-VEGF antibody cancer

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Characterization of a Novel Anti-DR5 Monoclonal Antibody WD1 with the Potential to Induce Tumor Cell Apoptosis

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Cellular & Molecular Immunology 2008年第1期5卷 55-60页

作者： Jing Wang Zhou Lin chunxia Qiao Ming lv Ming Yu He Xiao Qingyang Wang Liyan Wang Jiannan Feng Beifen Shen Yuanfang Ma Yan Li Laboratory of Cellular and Molecular Immunology Institute of Immunology Henan University Kaifeng China Institute of Basic Medical Sciences Beijing China These authors contributed equally to this work

TNF-related apoptosis-inducing ligand （TRAIL） is a TNF family member capable of inducing apoptosis. Death receptor 5 （DR 5） is a key receptor of TRAIL and plays an important role in TRAIL-induced apoptosis. To prepare monoclonal antibodies （mAbs） against DR5, cDNA encoding soluble DR5 （sDR5） was firstly amplified by reverse transcriptase-polymerase chain reaction （RT-PCR） with specific primers, and then inserted into a prokaryotic expression vector pET-30a. The recombinant plasmid was expressed in Escherichia coli strain BL21 （DE3）, and sDR5 was purified by nickel affinity chromatography. As an antigen, sDR5 was used to immunize mice. Hybridomas secreting antibodies against sDR5 were identified. One positive done was selected to produce antibody, WD1. ELISA and immunofluorescence demonstrated that WD1 could bind recombinant sDR5 and membranebound DR5 （mDR5） on Jurkat and Molt-4 cells. ATPLite assays showed that Jurkat and Molt-4 cells were sensitive to the antibody in a dose dependent manner. The Annexin V/PI assays and Giemsa＇s staining both showed that WD1 could induce Jurkat cell apoptosis efficiently. Transient transfection of 293T cells and indirect immunofluorescence assay demonstrated that mAb （WD1） couldn＇t cross-react with DR4. Our findings indicated that the novel antibody, WD1 could act as a direct agonist, bind DR5 characteristically, and initiate efficient apoptotic signaling and tumor regression. Thus, WD1 would be a leading candidate for potential cancer therapeutics. Cellular ＆ Molecular Immunology.

关键词： TRAIL death receptor 5 apoptosis monoclonal antibody ATPLite

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