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The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil

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Acta Pharmaceutica Sinica B 2014年第1期4卷 94-99页

作者： Youssef W.Naguib Amit Kumar zhengrong cui The University of Texas at Austin College of PharmacyPharmaceutics DivisionAustinTX 78712USA

Topical 5-fluorouracil(5-FU)is approved for the treatment of superficial basal cell carcinoma and actinic ***,5-FU suffers from poor skin *** have been successfully applied to improve the skin permeability of small and large molecules,and even nanoparticles,by creating micron-sized pores in the stratum corneum layer of the *** this report,the feasibility of using microneedles to increase the skin permeability of 5-FU was *** full thickness mouse skin mounted on Franz diffusion apparatus,it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles(500μm in length,50μm in base diameter).In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space,the antitumor activity of a commercially available 5-FU topical cream(5%)was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles,as compared to when the cream was simply applied on a skin area,underneath which the tumor cells were implanted,and without pretreatment of the skin with *** is not approved for melanoma therapy,but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.

关键词： Microneedles 5-Fluorouracil Cytotoxicity Melanoma Immunohistochemistry Flux Transdermal Antitumor activity Skin permeability

离心不耦合条件下寒区碎软岩体预裂爆破参数优化方法

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金属矿山 2024年第9期 161-166页

作者：潘祖瑛张西良仪海豹崔正荣杨海涛刘智兵中钢集团马鞍山矿山研究总院股份有限公司安徽马鞍山243000 马鞍山矿山研究院爆破工程有限责任公司安徽马鞍山243000 金属矿山安全与健康国家重点实验室安徽马鞍山243000

一般来说,预裂爆破采用同心不耦合装药结构,但由于药柱自身重力原因,药柱和炮孔壁贴合在一起,这种情况可能增强了对预裂爆破保留岩体的损伤。基于传统预裂爆破技术,结合理论分析,提出了离心不耦合装药条件下任意一点的不耦合系数计算公... 详细信息

一般来说,预裂爆破采用同心不耦合装药结构,但由于药柱自身重力原因,药柱和炮孔壁贴合在一起,这种情况可能增强了对预裂爆破保留岩体的损伤。基于传统预裂爆破技术,结合理论分析,提出了离心不耦合装药条件下任意一点的不耦合系数计算公式,推导出其与同心不耦合系数的关系,并比较了2种装药条件下预裂爆破对保留岩体的损伤情况。以白云鄂博西矿为例,在现有2种规格预裂药柱基础上,依据理论分析得出:在不改变预裂孔直径的前提下,当预裂药柱直径为60 mm时,需要对预裂孔孔距和预裂孔装药结构进行优化。通过开展现场试验,对预裂孔孔距和预裂孔装药结构进行了优化,得出了最佳孔网参数。通过三维倾斜摄影技术建立三维模型,对孔网参数优化前后的爆破效果进行了评价,孔网参数优化后半壁孔率提升了27.09%。研究表明:孔网参数优化后,对于保护采场边坡、维护边坡安全稳定具有积极作用,对于类似工程也有借鉴意义。

关键词：离心不耦合寒区碎软岩预裂爆破现场试验三维倾斜摄影

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大断面隧道掘进爆破分区优化设计研究

金属矿山 2024年第9期 142-150页

作者：汪禹张西良仪海豹李龙福崔正荣杨海涛吴林王潮汐金属矿山安全与健康国家重点实验室安徽马鞍山243000 马鞍山矿山研究院爆破工程有限责任公司安徽马鞍山243000 华唯金属矿产资源高效循环利用国家工程研究中心有限公司安徽马鞍山243000

某隧道工程地质、水文地质等条件均较复杂,采用原爆破设计施工方案(常规“两步”台阶法)常出现隧道断面超挖、冒顶等情况,严重制约了隧道工程建设,无法满足隧道工程建设目标,需对原设计方案参数进行优化调整。根据隧道断面规格、工程岩... 详细信息

某隧道工程地质、水文地质等条件均较复杂,采用原爆破设计施工方案(常规“两步”台阶法)常出现隧道断面超挖、冒顶等情况,严重制约了隧道工程建设,无法满足隧道工程建设目标,需对原设计方案参数进行优化调整。根据隧道断面规格、工程岩性等条件,为控制隧道顶板暴露面积、防止顶板冒落及降低支护成本等,优选“CRD法”“三步台阶”及“两步台阶”作业法,开展隧道爆破分区掘进试验研究,并严格控制隧道顶板周边孔布置间距(400~450 mm)。为降低隧道爆破数码电子雷管使用量,隧道顶部周边孔采用导爆索与32 mm乳化炸药绑扎(胶布缠绕),各炮孔间通过导爆索传爆,取代传统光面爆破参数。现场施工结果表明:Ⅴ级围岩隧道采用“CRD法”施工,顶部超、欠挖量满足技术规范;Ⅳ级围岩隧道采用“三步台阶”施工,炮孔残留率达60%~72%;Ⅲ级围岩隧道采用“两步台阶”施工,炮孔残留率达84%~94%。优化传统光面爆破参数布置,利用导爆索实现顶部周边孔孔间传爆、孔内起爆,可总体降低数码电子雷管使用量,降低爆破成本约18.5%,该技术可为类似隧道工程及地下矿山巷道掘进爆破提供参考。

关键词： CRD法台阶法施工光面爆破导爆索数码电子雷管

Tumor immunotherapy in the treatment of NSCLC

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Tumor immunotherapy in the treatment of NSCLC

第十二届全国免疫学学术大会

作者： SUN Xiaoying ZHENG Yuanqiang cui zhengrong SHI Yanchun Inner Mongolia Key Laboratory of Molecular Biology Inner Mongolia Medical University Pharmaceutics Division College of Pharmacythe University of Texas at Austin

Lung cancer is the leading cause of cancer mortality worldwide,accounting for 1.3 million deaths each ***-small cell lung cancer(NSCLC) accounts for approximately 80-85%of all lung cancers and is usually diagnosed at an advanced stage with poor *** chemoradiotherapy improves overall survival as compared to sequential chemotherapy and radiation therapy,but is associated with higher rates of *** has shown promising results in various types of ***,immune-checkpoint inhibitor(ICPI) drugs,which include antibodies against Cytotoxic T-Lymphocyte Antigen-4(CTLA-4),programmed cell death protein 1(PD-1) and programmed cell death protein ligand 1(PD-L1),have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced *** inhibitors are the most striking innovation in the clinical development of immunotherapy.T-cell checkpoint inhibitors that target the PD-1 and PD-L1 are changing the current strategy in the treatment of advanced NSCLC without driver gene mutations such as anti-PD-1/PD-L1,pembrolizumab,are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction.

关键词： NSCLC Tumor immunotherapy Immune check point Inhibitors PD-1/PD-L1

Lysosomes are Beneficial for(stearoyl) Gemcitabine-incorporated Solid Lipid Nanoparticles to Overcome Tumor Cell Chemoresistance

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Lysosomes are Beneficial for(stearoyl) Gemcitabine-incorpora...

第十三届全国免疫学学术大会

作者： Yanchun Shi Zhe Chen Yuanqiang Zheng zhengrong cui Inner Mongolia Key Laboratory of Molecular Biology School of Basic Medical Sciences Inner Mongolia Medical University Division of Molecular Pharmaceutics and Drug Delivery College of Pharmacy The University of Texas at Austin

Despite recent advances in targeted therapies and immunotherapies, chemotherapy using cytotoxic agents remains an indispensable modality in cancer ***, there has been a growing emphasis in using nanomedicine in cancer chemotherapy, and several nanomedicines have already been used clinically to treat *** is evidence that for mulating small molecular cancer chemotherapeutic agents into nanomedicines significantly modifies their pharmacokinetics and often improves their ***, cancer cells often develop resistance to chemotherapy, and formulating anticancer drugs into nanomedicines also helps overcome *** this review, we briefly describe the different classes of cancer chemotherapeutic agents, their mechanisms of action and resistance, and evidence of overcoming the resistance using *** then emphasize on gemcitabine and our experience in discovering the unique(stearoyl) gemcitabine solid lipid nanoparticles that are effective against tumor cells resistant to gemcitabine and elucidate the underlying mecha *** seems that lysosomes, which are an obstacle in the delivery of many drugs, are actu ally beneficial for our(stearoyl) gemcitabine solid lipid nanoparticles to overcome tumor cell resistance to gemcitabine.

关键词： gemcitabine chemoresistance chemotherapeutic agents nanomedicine

中青年冠心病患者健康素养量表的编制及信效度检验

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天津护理 2024年第2期32卷 132-137页

作者：贾媛王玉君高新星崔峥嵘郑碧锦赵金霞洪菲菲樊现岗郭建星天津医科大学第二医院天津300211 天津中医药大学护理学院天津中医药大学第一附属医院长治市人民医院

目的:编制中青年冠心病患者健康素养量表并检验其信效度,为医护人员对该群体的健康教育及管理提供参考。方法:基于Paasche-Orlow和Wolf健康素养模式和知识-态度-行为(KAP)理论,通过文献回顾、半结构式访谈、2轮专家咨询及预调查后形成... 详细信息

目的:编制中青年冠心病患者健康素养量表并检验其信效度,为医护人员对该群体的健康教育及管理提供参考。方法:基于Paasche-Orlow和Wolf健康素养模式和知识-态度-行为(KAP)理论,通过文献回顾、半结构式访谈、2轮专家咨询及预调查后形成初始量表;2022年9月至2023年1月便利选取204例中青年冠心病患者进行调查,对量表进行项目分析及信效度检验。结果:中青年冠心病患者健康素养量表包含3个维度,18个条目,条目水平内容效度指数为0.8~1.0,量表水平内容效度指数为0.952;共提取出资源获取与利用、医患沟通、自我护理3个公因子,各因子的条目载荷均>0.4,累计方差贡献率为69.001%;量表的Cronbach′s α系数为0.933,各维度的Cronbach′s α系数分别为0.919,0.865,0.920。结论:中青年冠心病患者健康素养量表具有良好的信效度,可用于评估中青年冠心病患者健康素养水平。

关键词：中青年冠心病健康素养量表编制

Gemcitabine derivative improved antitumor activity and potential to circumvent gemcitabine resistance

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Gemcitabine derivative improved antitumor activity and poten...

第十二届全国免疫学学术大会

作者： CHEN Zhe ZHENG Yuanqiang WU Lan cui zhengrong SHI Yanchun Inner Mongolia Key Laboratory of Molecular Biology Inner Mongolia Medical University Pharmaceutics Division College of Pharmacythe University of Texas at Austin

Gemcitabine(2’,2’-difluorodeoxycytidine) is a deoxycytidine analog with antitumor activity against a wide variety of solid tumors such as pancreatic,non-small cell lung,breast,and ovarian cancers,alone or in combination with other chemotherapeutic ***,short half-life due to extensive deamination at 4-amino site by action of cytidine deaminase(CDA),side effects and drug resistance limit its *** improve its antitumor efficacy and/or safety profiles,modification of gemcitabine was *** 4-amino groupand/or 5’position were usually *** main purpose of the synthesis of gemcitabine derivativemay involved(i) protect the 4-N group from deamination,(ii)deliver more therapeutics to tumorsand/orreduce toxicity,(iii) improve storage stability,(iv) possible apply in deoxycytidine kinase(dCK) deficient tumor cells and(v) overcome nucleoside transporters deficiency-based cancer cell ***,coupling of some compounds can significantly increase lipid solubility of gemcitabine,which is potential to circumvent gemcitabine resistance caused by decreased expression of nucleoside ***,Sobot and coworkers reported gemcitabine-squalene conjugate(SQ-Gem) encapsulated into nanoparticles,which were shown to be strongly interacted with the low-density lipoproteins(LDLs) in the human blood,and improved pharmacological *** prompted us to study the mechanism of gemcitabine derivative more *** review is intended to show the research progress of gemcitabine derivative,with a special emphasis on the application of gemcitabine derivativein overcoming cancer cell resistance to gemcitabine and its increased antitumor activity.

关键词： Gemcitabine gemcitabine derivative resistance antitumor activity

A Novel Research Strategy of Nanomedicines Targeting Tumorassociated Macrophages (TAMs) on Solid Tumors

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A Novel Research Strategy of Nanomedicines Targeting Tumoras...

第十一届全国免疫学学术大会

作者： SHI Yanchun WANG Cai Xia CHEN Zhe cui zhengrong ZHENG Yuanqiang Inner Mongolia Key Laboratory of Molecular Biology Inner Mongolia Medical University

The tumor microenvironment has an important influence on cancer biological and clinical behavior and ***-associated macrophages(TAMs)derived from peripheral blood monocytes have been confirmed to play an important rol... 详细信息

关键词： Nanomedicine Tumor-associated macrophages Gemcitabine Solid tumor

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基于层级约束的多无人车编队包含控制

汽车工程 2023年第8期45卷 1333-1342页

作者：吴其林林育明崔峥嵘赵晓敏合肥学院先进制造工程学院合肥230601 合肥工业大学汽车与交通工程学院合肥230009

针对多无人系统的编队包含控制问题,本文提出一种自适应鲁棒控制方法。针对系统中的领航者层和跟随者层分别设计对应的编队、包含以及避撞行为约束,并由Udwadia-Kalaba方程求得满足约束所需的理想驱动力。通过渐亏型自适应律估计系统的... 详细信息

针对多无人系统的编队包含控制问题,本文提出一种自适应鲁棒控制方法。针对系统中的领航者层和跟随者层分别设计对应的编队、包含以及避撞行为约束,并由Udwadia-Kalaba方程求得满足约束所需的理想驱动力。通过渐亏型自适应律估计系统的不确定参数,从而补偿不确定性影响。然后,采用李雅普诺夫函数方法验证了所设计控制的稳定性。最后,数值仿真结果显示:含时变不确定性的受控系统在完成编队包含行为的同时无任何碰撞发生。

关键词：约束编队包含控制自适应鲁棒控制不确定性