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Acta Pharmaceutica Sinica B 2024年第3期14卷 1400-1411页

作者： Shuo wang Tian Liu Yuetong Huang Chaoying Du Danping wang xiyan wang Qingzhi Lv Zhonggui He Yinglei Zhai Bingjun Sun Jin Sun Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Binzhou Medical UniversityBinzhou 256600China

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly *** the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug *** study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’*** extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative *** use of C_(20) can balance efficacy and *** results provide a great reference for the rational design of prodrug nanoassemblies.

关键词： Prodrugs Nanoassemblies Self-assembly Branched-chain fatty alcohols Disulfide bond Docetaxel Efficacy Safety

Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 188-203页

作者： Mingyang Zhang Yifan Miao Can Zhao Tong Liu xiyan wang Zixuan wang Wenxin Zhong Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province Hangzhou 310058China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China Liaoning Provincial Institute of Drug Inspection and Testing Shenyang 110036China

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

关键词： Steric disulfide bond Triglyceride-like pr odrugs Cabazitaxel Lymphatic transport Oral chemotherapy

Measurement and Correlation of Pressure Drop for Gas-Liquid Two-phase Flow in Rectangular Microchannels

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Chinese Journal of Chemical Engineering 2010年第6期18卷 940-947页

作者： MA Youguang JI xiyan wang Dongji FU Taotao ZHU Chunying School of Chemical Engineering and Technology State Key Laboratory of Chemical Engineering Tianjin University Tianjin 300072 China

The pressure drop of gas-liquid two-phase flow in microchannel is of fundamental importance in heat and mass transfer processes. In this work,the pressure drop of gas-liquid two-phase flow in horizontal rectangular cross-section microchannels was measured by a pressure differential transducer system. Water,ethanol and n-propanol were used as liquid phase to study the effects of capillary number on pressure drop;air was used as the gas phase. Four microchannels with various dimensions of 100 μm× 200 μm,100 μm× 400 μm,100 μm× 800 μm and 100 μm× 2000 μm(depth × width) were used for determining the influence of configuration on the pressure drop. Experimental results showed that in micro-scale,the capillary number also affected the pressure drop remarkably,and in spite of only one-fold difference in aspect ratio,the variation of pressure drop reached up to near three times under the same experimental conditions. Taking the effects of aspect ratio and surface tension into account,a modi-fied correlation for Chisholm parameter C in the Chisholm model was proposed for predicting the frictional multi-plier,and the predicted values by the proposed correlation showed a satisfactory agreement with experimental data.

关键词： pressure drop rectangular cross-section microchannel surface tension configuration influence Chis-holm parameter C

Congenital factor XI deficiency:a retrospective analysis of 80 cases

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China Medical Abstracts(Internal Medicine) 2021年第3期38卷 182-183页

作者： wang xiyan State Key Hematol Lab Natl Clin Blood Dis Res CenterInstit Hematol&Blood Dis HospCAMS&PUMCTianjin 300020

Objective To analyze the clinical manifestation,laboratory examination,treatment and prognosis of congenital factor XI(F XI)*** The clinical data of 80 patients with congenital FXI deficiency in our hospital from Sept... 详细信息

关键词： clinical congenital prognosis

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木麻黄和缅甸蟒——另一种遗产逻辑

开放时代 2022年第6期 210-221页

作者：王希言法国社会科学高等研究院

本研究基于作者在2018年—2019年间针对“金门岛的战后遗产化”所开展的田野调查,梳理和分析了当地政府、知识分子、老百姓之间对于木麻黄和缅甸蟒两个物种能否作为自然遗产的争议。这两个案例为我们探究非西方语境下的处于社会转型期... 详细信息

本研究基于作者在2018年—2019年间针对“金门岛的战后遗产化”所开展的田野调查,梳理和分析了当地政府、知识分子、老百姓之间对于木麻黄和缅甸蟒两个物种能否作为自然遗产的争议。这两个案例为我们探究非西方语境下的处于社会转型期中不同人群的遗产保护逻辑提供了样本,即,“情感”和“记忆”如何参与到遗产的鉴别之中,以及如何塑造另一种人类和“非人类”的关系模式。

关键词：生态保护遗产情感记忆

维普期刊数据库博看期刊

Regeneration and identification of interspecific asymmetric somatic hybrids obtained by donor-recipient fusion in cotton

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Chinese Science Bulletin 2009年第15期54卷 3035-3044页

作者： FU LiLi YANG xiyan ZHANG XianLong wang ZhiWei FENG ChangHui LIU ChuanXiang JIANG Pei-Yong ZHANG JinLong National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural University Wuhan 430070 China

Asymmetric hybrids between Gossypium hirsutum (YZ-1) and G. davidsonii were obtained by donor-recipient fusion. YZ-1 was considered the recipient and was pretreated with iodoacetamide (IOA), while G. davidsonii was considered the donor and was irradiated with ultraviolet (UV) before fusion. YZ-1 protoplasts stopped growth when treated with 0.5 mmol/L IOA for 20 min, and G. davidsonii protoplasts stopped growth when irradiated with 38.7 J/cm2 UV for 30 s. Asymmetric somatic hybrids were obtained by electrofusion between the separately treated protoplasts of the 2 species. The regenerated plants were identified by morphological, cytological, and molecular analysis. Most regenerated plants derived from fused protoplasts displayed new morphology; some were intermediate between the two parents and a few displayed recipient-like morphology. Chromosome numbers in these somatic hybrids mostly ranged from 40 to 73. The hybridity was confirmed by random amplified polymorphic DNA and simple sequence repeat analysis. Organelle DNA inheritance of the YZ-1 and G. davidsonii somatic hybrid was investigated by cleaved amplified polymorphism sequence and chloroplast simple sequence repeat analysis, which indicated that recombination and rearrangements might have occurred in some regions of mitochondrial and chloroplastic DNA. This is the first report of completely asymmetric hybrid production via donor–recipient fusion between G. hirsutum and G. davidsonii, which is a novel case in hybrid production following the symmetric fusion and asymmetric fusion based on UV irradiation in cotton.

关键词：不对称体细胞杂交融合识别棉花种间再生

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Expressions of Survivin and Caspase-3 in human hepatocellular carcinoma and the relationship with prognosis

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The Chinese-German Journal of Clinical Oncology 2010年第11期9卷 628-632页

作者： Wei Ding Wei Hu xiyan wang Xiaogang Dong Department of Hepatobiliopancreatic Surgery Tumor Hospital Affiliated to Xinjiang Medical University Urumqi 830011 China

Objective: The aim of our study was to investigate the expressions of Survivin and Caspase-3 in the hepatocellular carcinoma (HCC) and the paracancerous liver tissues, and define the relationship between the expression and the patients survival rate after surgery. Methods: The expressions of PCNA, Survivin and Caspase-3 were detected by immunohistochemistry. PCNA positive level was used to account proliferating cell nuclear antigen proliferating index (PCNA-PI). The apoptosis index of HCC tissues was detected by TUNEL. Results: The expression of Survivin in HCC tissue was higher than that in paracancerous tissue (P < 0.05), while it was related with portal vein thrombosis, tumor size and histological differentia- tion (P < 0.05). In HCC tissues, the PCNA-PI of the Survivin positive group was higher than the negative (P < 0.05) group, and the AI of the Survivin positive group was lower than the negative group (P < 0.05). The expression of Caspasse-3 in HCC tissue was lower than that in paracancerous tissue (P < 0.05), while it was related with HBsAg and histological differentiation (P < 0.05). In HCC tissues, the average PCNA-PI of the Caspase-3 positive group was lower than that of the negative group (P < 0.05), and the average AI of the Caspase-3 positive group was higher than that of the negative group (P < 0.05). There was negative correlation between the expressions of Survivin and Caspase-3 in HCC (r = -0.242, P < 0.05). The survival rate of the Survivin positive group was lower than that of the negative group (P < 0.05), while that of the Caspase-3 positive patients was higher than that of the negative group (P < 0.05). Conclusion: The expressions of Survivin and Caspase-3 in HCC can reflex the biological behavior of HCC and patients prognosis, they may be new targets of tumor diagnosis and treatment.

关键词： HCC Survivin Caspase-3 proliferation apoptosis

Understanding of the Growth Mechanisms of Hierarchical Biomineral Structures

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Understanding of the Growth Mechanisms of Hierarchical Biomi...

第十六届全国晶体生长与材料学术会议

作者： Guobin Ma Yifei Xu xiyan wang Mu wang Xiang Yang Liu National Laboratory of Solid State Microstructures and School of PhysicsNanjing University Department of Physics Faculty of ScienceNational University of Singapore2 Science Drive 3Singapore 117542

Ordered hierarchical structures based on one-or two-dimensional nanocrystals have significant potential applications in nano lasers,solar cells,catalysis,drug delivery,and self-cleaning,*** represents an efficient bottom-up strategy to fabricate the hierarchical *** systems provide numerous examples of well-organized inorganic materials that directly develop into

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来源： cnki会议评论

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开征房产税能够降低房价并替代土地财政吗?

河北经贸大学学报 2017年第6期38卷 55-62页

作者：柴国俊王希岩河北经贸大学商学院河北石家庄050061 北京交通大学中国产业安全研究中心北京100044

以往文献认为,征收房产税会抑制房价,但鲜有学者探究该政策作用的具体时间效应及土地市场综合效果。基于2008—2013年上海和南京、重庆和成都两组城市的区级数据,利用双重差分及事件研究方法实证考察研究发现,实施房产税总体上对住房价... 详细信息

以往文献认为,征收房产税会抑制房价,但鲜有学者探究该政策作用的具体时间效应及土地市场综合效果。基于2008—2013年上海和南京、重庆和成都两组城市的区级数据,利用双重差分及事件研究方法实证考察研究发现,实施房产税总体上对住房价格有显著的提升作用,但会随着时间推移而下降;征税还能够降低住房成交量,同时对土地均价和土地出让金具有负向影响;房产税在上海的试点效果和总体一致,但对重庆的影响不显著甚至与预期相反。

关键词：房产税土地财政房地产市场双重差分法事件研究

长效重组凝血因子Ⅸ药物治疗血友病B研究进展

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中华血液学杂志 2022年第3期43卷 259-264页

作者：王夕妍杨仁池中国医学科学院血液病医院(中国医学科学院血液学研究所) 实验血液学国家重点实验室国家血液系统疾病临床医学研究中心细胞生态海河实验室天津市血液病基因治疗研究重点实验室中国医学科学院血液病基因治疗重点实验室天津300020

血友病B是一种以凝血因子Ⅸ(FⅨ)缺乏为特征的X染色体连锁的隐性遗传性出血性疾病,主要表现为关节、肌肉及深部组织自发和创伤性出血。血友病B的主要治疗方法是FⅨ替代治疗,首选基因重组FⅨ(rFⅨ)或病毒灭活的血源性凝血酶原复合物(PCC)... 详细信息

血友病B是一种以凝血因子Ⅸ(FⅨ)缺乏为特征的X染色体连锁的隐性遗传性出血性疾病,主要表现为关节、肌肉及深部组织自发和创伤性出血。血友病B的主要治疗方法是FⅨ替代治疗,首选基因重组FⅨ(rFⅨ)或病毒灭活的血源性凝血酶原复合物(PCC),无上述条件时可选用新鲜冰冻血浆等[1-2]。尽管目前应用的FⅨ制剂具有良好的疗效和安全性,但由于FⅨ半衰期较短,需要每周注射2~3次以维持保护性浓度,会造成静脉通路问题,同时加重患者经济负担,严重影响患者的依从性和治疗结局[3]。因此,临床上对于改进血友病B的治疗有着迫切的需求,即需要更长的半衰期和更优化的药代动力学特征药物以进一步改进血友病B的治疗模式。

关键词：血友病B 新鲜冰冻血浆静脉通路深部组织疗效和安全性凝血因子Ⅸ 血源性创伤性出血