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Bone marrow mesenchymal stem cells-derived exosomes for penetrating and targeted chemotherapy of pancreatic cancer

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1563-1575页

作者： Yu Zhou Wenxi Zhou xinli chen Qingbing Wang Chao Li Qinjun chen Yu Zhang Yifei Lu Xiaoyi Ding chen Jiang Department of Interventional Radiology Ruijin HospitalShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China Key Laboratory of Smart Drug Delivery Ministry of EducationState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 200032China

Pancreatic ductal adenocarcinoma(PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix(ECM). Based on the theory that bone marrow mesenchymal stem cells(BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes(Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel(PTX) and gemcitabine monophosphate(GEMP)-an intermediate product of gemcitabine metabolismd-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy in vivo and in vitro, plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance(Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.

关键词： targeted metabolism chemotherapy

Substance P-modified human serum albumin nanoparticles loaded with paclitaxel for targeted therapy of glioma

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Acta Pharmaceutica Sinica B 2018年第1期8卷 85-96页

作者： Chunhui Ruan Lisha Liu Yifei Lu Yu Zhang Xi He xinli chen Yujie Zhang Qinjun chen Qin Guo Tao Sun chen Jiang Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Medical NeurobiologyDepartment of Pharmaceutics School of Pharmacy Fudan University

The blood–brain barrier(BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme(GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel(PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles(NPs). Here we characterize PTX-loaded human serum albumin(HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P(SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content(7.89%) and entrapment efficiency(85.7%) with a spherical structure(about 150 nm) and zeta potential of -12.0 mV. The in vitro drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells(BCECs) and U87 cells was greatly *** low IC_(50), prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.

关键词： Human serum albumin Paclitaxel Drug delivery Substance P Blood–brain barrier Glioma

GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy

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Acta Pharmaceutica Sinica B 2019年第4期9卷 832-842页

作者： Qin Guo Chao Li Wenxi Zhou xinli chen Yu Zhang Yifei Lu Yujie Zhang Qinjun chen Donghui Liang Tao Sun chen Jiang Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Medical Neurobiology Department of Pharmaceutics School of Pharmacy Fudan University

Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for *** purpose of this work is to construct a self-assembled glutathione(GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription(RCT) method. GSH-responsive cationic polymer polyethyleneimine(pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid(DHA), a targeting molecule, which is a substrate of glucose transporter 1(GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.

关键词： MiRNA21 Dehydroascorbic acid Rolling circle transcription Self-assembly RNAi nanoparticle Tumor-targeting Nanomedicine Cancer treatment

A New Method for Comprehensive Evaluation of Air Quality in Urban Agglomeration

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Atmospheric and Climate Sciences 2021年第3期11卷 547-562页

作者： Li Lei xinli chen Wei Liu Business School Jiangnan University Wuxi China School of Social Development and Public Policy Fudan University Shanghai China School of Internet of Things Engineering Jiangnan University Wuxi China

In this study, a new method for a comprehensive evaluation of air quality in urban agglomerations was developed based on a prototype used to solve the spatial Steiner-Weber point. With this method, the air quality information of each city in the city group is aggregated into an optimal gathering point, and then the air quality of the city group is then dynamically evaluated each year. According to the relevant data of the China Statistical Yearbook 2018, we applied this method to aggregate the air quality indices of the major cities in the Beijing-Tianjin-Hebei urban agglomeration from 2014 to 2017. Using the plant growth simulation algorithm (PGSA), the optimal assembly points were calculated to be of a higher accuracy, compared to the traditional mean value aggregation method. Finally, the air quality of the Beijing-Tianjin-Hebei urban agglomeration during each year was evaluated dynamically based on the obtained assembly points. The results show that the air quality of the urban agglomeration is ranked as follows: Y2016Y2015Y2017Y2014.

关键词： Urban Agglomeration Air Quality Optimal Information Aggregation Dynamical Evaluation Plant Growth Simulation Algorithm

Modified Maze lines plus pulmonary vein isolation created by radiofrequency catheter ablation on the atrial wall to treat atrial fibrillation in elderly

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Journal of Geriatric Cardiology 2005年第2期2卷 95-100页

作者： Caiyi LU Shiwen WANG Xinping DU Yinglong HOU Qiao XUE xinli WU Rui chen Peng LIU The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China The Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China

Objective To evaluate the effect of modified Maze lines plus pulmonary vein (PV) isolation created by radiofrequency catheter ablation (RFCA) on atrial wall guided by a novel geometry mapping system in the treatment of elderly patients with paroxysmal atrial fibrillation (PAF). Methods After regular electrophysiological study, transseptal punctures were achieved twice with Swartz L1 and R1 sheaths. PV angiographies were conducted to evaluate their orifices and branches. A balloon electrode array catheter with 64 electrodes was put in the middle of the left atrium. Atrium geometry was constructed using Ensite 3000 Navx system. Two RFCA lesion loops and three lines (modified Maze) were created on left and right atrial walls. Each lesion point was ablated for 30 seconds with preset temperature 50 (ae) and energy 30W. The disappearance or 80% decrease of the amplitude of target atrial potential and 10 to 20(|), decrease of ablation impedance were used as an index of effective ablation. Results A total of 11 patients (7 male and 4 female, mean age, 68.7±5.1 years) were enrolled. PAF history was 7.9±4.5 years. PAF could not be prevented by mean 3.1±1.6 antiarrhythmic agents in 6.3±3.4 years. None of the patients had complications with structural heart disease or stroke. Left atrial diameter was 41.3±3.6 mm and LVEF was 59.2±3.7% on echocardiography. Two loops and three lines were completed with 67.8±13.1 (73-167) lesion points. Altogether 76-168 (89.4±15.3) lesion points were created in each patient. PAF could not be provoked by rapid burst pacing up to 600 beat per minute delivered from paroxysmal coronary sinus electrode *** PV electrical isolation was confirmed by three-dimensional activation mapping. Mean procedure time was 2.7±0.6 hours and fluoroscopy time was 17.8±9.4 minutes. Patients were discharged with oral aspirin and without antiarrhythmic agents. During follow up of 6.5±1.8 months, seven patients were PAF symptom free (63.6%). PAF attacks were decr

关键词： paroxysmal atrial fibrillation electrophysiology MAZE ablation pulmonary vein ablation

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法国海权兴衰及战略研究述略

太平洋学报 2016年第9期24卷 55-63页

作者：陈新丽冯传禄华中科技大学湖北武汉430074 武汉大学湖北武汉430072

近代以降,法国的海权兴衰与其国家命运密切交织,其经验与教训并存,并也因此而成为诸多国外研究者思考海权理论、海军战略的重要历史素材。同时,法国作为陆海复合型国家最具代表性者之一,其海权思想对世界海权理论发展也有自身独特贡献... 详细信息

近代以降,法国的海权兴衰与其国家命运密切交织,其经验与教训并存,并也因此而成为诸多国外研究者思考海权理论、海军战略的重要历史素材。同时,法国作为陆海复合型国家最具代表性者之一,其海权思想对世界海权理论发展也有自身独特贡献。但迄今国内学界关于法国海权的研究和成果仍显零散,且存在相关认知误区。今日,中国面向海洋的发展战略面临转型,迫切需要相关理论供给和经验借鉴,因此,对以法国为代表的陆海复合型国家的海权发展和战略研究确有重视和加强之必要。

关键词：法国海权研究研究综述

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天友绿色设计中心超低能耗设计与运行研究

暖通空调 2015年第3期45卷 9-15页

作者：何青陈鑫力天友建筑设计股份有限公司

探讨了绿色建筑节能项目如何在被动式节能技术优先的条件下发挥主动式节能技术的作用和效能,从而降低建筑能耗。重点介绍了主动式节能技术的三要素——低碳节能的冷热源、多种高效节能的空调末端和全面自控监测系统,以及所采取的主动式... 详细信息

探讨了绿色建筑节能项目如何在被动式节能技术优先的条件下发挥主动式节能技术的作用和效能,从而降低建筑能耗。重点介绍了主动式节能技术的三要素——低碳节能的冷热源、多种高效节能的空调末端和全面自控监测系统,以及所采取的主动式节能运行策略。结合被动式与主动式节能技术在该项目中的实际应用效果,倡导绿色建筑应从满足人体舒适度和降低能耗需求的角度出发,采用合理的运行策略使两种节能技术相融合,从而实现理想的节能效果。

关键词：绿色建筑被动式节能技术主动式节能技术舒适度节能低碳运行策略