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Rationale and design of Patient-centered Retrospective Observation of Guideline-Recommended Execution for Stroke Sufferers in China: China PROGRESS

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Stroke & Vascular Neurology 2019年第3期4卷 165-170页

作者： Zixiao Li Chunjuan wang Yong Jiang Xinmiao Zhang Ying Xian Liping Liu Xingquan Zhao Hongqiu Gu Xia Meng Hao Li Yilong wang yongjun wang Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Center of Stroke Beijing Institute for BrainDisordersBeijingChina Beijing Key Laboratory of Translational Medicine forCerebrovascular Disease BeijingChina Duke Clinical Research Institute North CarolinaUSA Neuro-intensive Care Unit Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina

Background In 2009,China launched ambitious healthcare reform plans to provide affordable and equitable basic healthcare for all patients,including the substantial number of patients who had a ***,little is known about the pattern of evidence-based stroke care and outcomes across hospitals,regions and time during the last *** The Patient-centered Retrospective Observation of Guideline-Recommended Execution for Stroke Sufferers in China(China PROGRESS)Study aims to use findings from a representative sample of Chinese hospitals over the last decade to improve future stroke care for patients hospitalised with ischaemic stroke(IS)or transient ischaemic attack(TIA).Design The China PROGRESS Study will use a two-stage cluster sampling method to identify over 32000 patient records from 208 hospitals across the Eastern,Central and Western geographical regions in *** assess the temporal trends in patient characteristics,treatment and outcomes,study investigators will select records from 2005,2010 and 2015.A double data reading/entry system will be developed to conduct this assessment.A central coordinating centre will monitor case ascertainment,data abstraction and data *** will examine patient characteristics,testing patterns,in-hospital treatment and outcomes,and variations across regions and across *** The China PROGRESS Study is the first nationally representative study that aims to better understand care quality and outcomes for patients with IS or TIA before and after the national healthcare reform in *** initiative will translate findings into clinical practices that improve care quality for patients who had a stroke and policy recommendations that allow these changes to be implemented *** approval This study has also been approved by the central institutional review board(IRB)at Beijing Tiantan Hospital.

关键词： PROGRESS Observation centered

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补骨脂素对环磷酰胺抑制小鼠骨髓间充质干细胞成骨分化的恢复作用

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中国组织工程研究 2025年第1期29卷 16-23页

作者：王成龙杨志烈常君丽赵永见赵东峰戴薇薇吴宏进张婕王利波谢颖唐德志王拥军杨燕萍上海中医药大学附属龙华医院科技中心实验室上海市200032 上海中医药大学附属龙华医院脊柱病研究所上海市200032 上海中医药大学附属龙华医院中医外科研究所上海市200032

背景:补骨脂素具有很强的抗骨质疏松活性,可能对化疗导致的骨质疏松具有恢复作用。目的:探讨补骨脂素对环磷酰胺抑制小鼠骨髓间充质干细胞成骨分化的恢复作用及机制。方法:分离培养C57BL/6小鼠骨髓间充质干细胞,以MTT法检测补骨脂素对... 详细信息

背景:补骨脂素具有很强的抗骨质疏松活性,可能对化疗导致的骨质疏松具有恢复作用。目的:探讨补骨脂素对环磷酰胺抑制小鼠骨髓间充质干细胞成骨分化的恢复作用及机制。方法:分离培养C57BL/6小鼠骨髓间充质干细胞,以MTT法检测补骨脂素对骨髓间充质干细胞活力的影响,以成骨诱导结合碱性磷酸酶染色确定补骨脂素对环磷酰胺抑制骨髓间充质干细胞成骨分化恢复作用的最佳剂量。采用RT-qPCR法检测补骨脂素干预不同时间点成骨分化标志基因Runx2、ALP、Osteocalcin、骨保护素及Wnt/β-catenin信号通路相关基因Wnt1、Wnt4、Wnt10b、β-catenin、c-MYC的mRNA表达;采用Western blot法检测补骨脂素干预不同时间点成骨特异性转录因子Runx2及Wnt/β-catenin信号通路相关基因Activeβ-catenin、DKK1、c-MYC、Cyclin D1的蛋白表达。结果与结论:(1)不同浓度补骨脂素对骨髓间充质干细胞活力没有显著影响;200μmol/L补骨脂素干预后对环磷酰胺诱导骨髓间充质干细胞成骨分化抑制的恢复作用最佳;(2)补骨脂素可以逆转环磷酰胺条件培养基导致的骨髓间充质干细胞成骨标志基因Runx2、ALP、Osteocalcin、骨保护素mRNA表达和Runx2蛋白表达的降低;(3)补骨脂素可以逆转环磷酰胺条件培养基导致的骨髓间充质干细胞Wnt/β-catenin通路相关基因Wnt4、β-catenin、c-MYC mRNA表达和Activeβ-catenin、c-MYC、Cyclin D1蛋白表达的降低以及DKK1蛋白表达的升高;(4)结果表明,环磷酰胺能抑制小鼠骨髓间充质干细胞成骨分化,补骨脂素对其具有恢复作用,且200μmol/L补骨脂素干预效果最佳,而这种保护作用可能与补骨脂素激活Wnt4/β-catenin信号通路有关。

关键词：环磷酰胺骨髓间充质干细胞成骨分化补骨脂素 Wnt4 β-catenin

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Polyphyllin Ⅰ enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth via downregulating the Wnt/β-catenin pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 251-259页

作者： CHANG Junli ZHAO Fulai SUN Xingyuan MA Xiaoping ZHAO Peng ZHOU Chujie SHI Binhao GU Wenchao wang yongjun YANG Yanping Spine Disease Institute Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China Department of Diagnostic and Interventional Radiology University of TsukubaIbaraki 315-0114Japan

OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling ***:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry *** morphology of cancer cells was observed with inverted phase contrast *** migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell *** expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting ***:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma *** synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling ***:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.

关键词： osteosarcoma tumor necrosis factor-related apoptosis-inducing ligand Wnt signaling pathway beta-catenin polyphyllinⅠ

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Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence

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Stroke & Vascular Neurology 2020年第2期5卷 116-120页

作者： Wanliang Du Xingquan Zhao Yilong wang Yuesong Pan Gaifen Liu Anxin wang Ruijun Ji Liping Liu Hongqiu Gu Kehui Dong Penglian wang yongjun wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease BeiingChina Center of Stroke Beijing Institute for Brain DisordersBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina

Objective Gastrointestinal(GI)bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of ***,it is unknown whether GI bleeding increases risk for recurrence of *** this study,we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke(AIS),using the China National Stroke Registry(CNSR).Methods This study included 22216 patients who had an ischaemic stroke included in the CNSR from 2007 to *** analysed baseline patient characteristics,GI bleeding and outcomes of patients who had an AIS,specifically stroke recurrence at 3,6 and 12 *** used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke *** Of the 12415 patients included in our study,12.3%,15.5%and 17.7%had a stroke recurrence at 3,6 and 12 months,*** bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months(adjusted OR 1.481,95%CI 1.118 to 1.962),6 months(adjusted OR 1.448,95%CI 1.106 to 1.896)and 12 months(adjusted OR 1.350;95%CI 1.034 to 1.763).Conclusion GI bleeding was associated with the increased risk of stroke recurrence after an AIS.

关键词： bleeding Gastrointestinal acute

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Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-Ⅱ (TRACE Ⅱ): rationale and design

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Stroke & Vascular Neurology 2022年第1期7卷 71-76页

作者： Shuya Li Bruce C V Campbell Lee H Schwamm Marc Fisher Mark Parsons Hao Li Yuesong Pan yongjun wang China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Medicine and Neurology University of MelbourneMelbourneVictoriaAustralia Department of Neurology and Comprehensive Stroke Center Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology Liverpool HospitalSouth Western Sydney Clinical SchoolSydneyNew South WalesAustralia

Background and purpose Tenecteplase(TNK)is a promising agent for treatment of acute ischaemic stroke(AIS).We hypothesised that recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)is non-inferior to rt-PA in achieving excellent functional outcome at 90 days,when administered within 4.5 hours of ischaemic stroke *** and design Tenecteplase Reperfusion therapy in Acute ischemic Cerebrovascular Events(TRACE)is a phase Ⅲ,multicentre,prospective,randomised,open-label,blinded-end point non-inferiority *** eligible for intravenous thrombolysis therapy are randomised to rhTNK-tPA 0.25 mg/kg(single bolus)to a maximum of 25 mg or rt-PA 0.9 mg/kg(10%bolus+90%infusion/1 hour)to a maximum of 90 *** considered necessary for the patient’s health may be given at the discretion of the investigator during 90-day *** outcomes The primary study outcome is excellent functional outcome defined as modified Rankin Scale(mRS)0–1 at 90 *** efficacy outcomes include favourable functional outcome defined as mRS≤2 at 90 days,ordinal distribution of mRS and major neurological improvement on the National Institutes of Health Stroke *** outcomes are symptomatic intracranial haemorrhage within 36 hours and death from any *** There is no completed registration study of TNK in AIS *** Ⅱ strives to provide evidence for a new drug application for rhTNK-tPA in AIS within 4.5 hours through a well-designed and rigorously executed randomised trial in China.

关键词： infusion acute rational

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Detailed phenotype of RNF213 p.R4810K variant identified by the Chinese patients with acute ischaemic stroke or transient ischaemic attack

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Stroke & Vascular Neurology 2023年第6期8卷 503-510页

作者： Hongyu Zhou Jing Jing Yuehua Pu Wei Li Xia Meng Anxin wang Yingting Zuo Zhe Xu Qin Xu Yue Suo Hao Li yongjun wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Tiantan Neuroimaging Center of Excellence Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Monogenic Disease Diagnosis Center for Neurological Disorders and Precision Medicine Research Center for Neurological Disorders Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina Center of excellence for Omics Research(CORe) Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina

Background and purpose The ring finger protein 213 gene(RNF213)p.R4810K variant increased the risk of acute ischaemic stroke(AIS)attributable to intracranial arterial stenosis(ICAS)in the Japanese and Korean *** this study,we aimed to examine the prevalence of the RNF213 p.R4810K variant in Chinese patients with AIS or transient ischaemic attack and identify the phenotype of the *** We analysed data from the Third China National Stroke *** included participants were divided into two groups by carrier status of the p.R4810K *** aetiological classification was conducted according to the Trial of Org 10172 in Acute Stroke Treatment(TOAST)*** presence of ICAS and extracranial arterial stenosis(ECAS)was defined as 50%-99%stenosis or occlusion of any intracranial and extracranial *** regression models and Cox regression models were used to evaluate the association of the p.R4810K variant with TOAST classification,stenosis phenotypes and clinical *** A total of 10381 patients were enrolled,among which 56(0.5%)had the heterozygote GA genotype for *** variant carriers were younger(p=0.01),and more likely to suffer from peripheral vascular disease(p=0.04).The p.R4810K variant was associated with large-artery atherosclerosis(LAA)(adjusted OR=1.94,95%CI 1.13 to 3.33),anterior circulation stenosis(adjusted OR=2.12,95%CI 1.23 to 3.65)and ECAS(adjusted OR=2.29,95%CI 1.16 to 4.51).Nevertheless,the p.R4810K variant was not associated with recurrence,poor functional outcome and mortality at 3 months and 1 *** The RNF213 p.R4810K variant was associated with LAA,anterior circulation stenosis and ECAS in Chinese *** the low carrying rate and only 1-year follow-up information,caution should be taken to interpret our findings in no statistically significant association between the p.R4810K variant and stroke prognosis in Chinese patients.

关键词： patients transient younger

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Clopidogrel with aspirin in High- risk patients with Acute Non- disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial

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Stroke & Vascular Neurology 2021年第2期6卷 280-285页

作者： yongjun wang Claiborne Johnston Philip M Bath Xia Meng Jing Jing Xuewei Xie Anxin wang Yuesong Pan Anding Xu Qiang Dong Yilong wang Xingquan Zhao Zixiao Li Hao Li Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina The University of Texas at Austin Dell Medical School AustinTexasUSA Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK Department of Neurology The First Affiliated HospitalJinan University GuangzhouGuangzhouGuangdongChina Department of Neurology Huashan HospitalState Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Background In patients with a minor ischaemic stroke or transient ischaemic attack(TIA),separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin(clopidogrel-aspirin)or ticagrelor plus aspirin(ticagrelor-aspirin)are more effective than aspirin alone in stroke secondary ***,these two sets of combination have not been directly *** clopidogrel was less effective in stroke patients who were CYP2C19 loss-of function(LOF)allele carriers,whether ticagrelor-aspirin is clinically superior to clopidogrel-aspirin in this subgroup of patients with stroke is *** To describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events(CHANCE-2)*** CHANCE-2 is a randomised,double-blind,double-dummy,placebo-controlled,multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are CYP2C19 LOF allele carriers:ticagrelor(180 mg loading dose on day 1 followed by 90 mg twice daily on days 2-90)or clopidogrel(300 mg loading dose on day 1 followed by 75 mg daily on days 2-90),plus open-label aspirin with a dose of 75-300 mg on day 1 followed by 75 mg daily on day *** will be followed for 1 *** outcomes The primary efficacy outcome is any stroke(ischaemic or haemorrhagic)within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 *** The CHANCE-2 trial will evaluate whether ticagrelor-aspirin is superior to clopidogrel-aspirin for minor stroke or TIA patients who are CYP2C19 LOF allele carriers.

关键词： CYP2C19 aspirin patients

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The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

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Asian Journal of Pharmaceutical Sciences 2017年第3期12卷 285-291页

作者： Zhenbao Li Wenhui Tao Dong Zhang Chunnuan Wu Binbin Song Shang wang Tianyang wang Mingming Hu Xiaohong Liu yongjun wang Yinghua Sun Jin Sun School of Pharmacy Shenyang Pharmaceutical UniversityNo.103Wenhua RoadShenyang 110016China Tianjin Medical University Cancer Hospital Tianjin 300060China China Resources Double-crane Pharmaceutical Co. Ltd.No.1Wangjing Lize East RoadChaoyang DistrictBeijingChina. Municipal Key Laboratory of Biopharmaceutics School of PharmacyShenyang Pharmaceutical UniversityNo.103Wenhua RoadShenyang 110016China

A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGANPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.

关键词： Atorvastatin calcium AC-PLGA-NPs Probe ultrasonication and evaporation method Oral bioavailability

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Neuromodulation-Based Stem Cell Therapy in Brain Repair:Recent Advances and Future Perspectives

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Neuroscience Bulletin 2021年第5期37卷 735-745页

作者： Ti-Fei Yuan Yi Dong Li Zhang Jieyu Qi Chun Yao yongjun wang Renjie Chai Yan Liu Kwok-Fai So Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China State Key Laboratory of Brain and Cognitive Sciences the University of Hong KongJiulongHong Kong SARChina Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education East China Normal UniversityShanghai 200241China Joint International Research Laboratory of CNS Regeneration Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhou 510632China Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhou 510632China Key Laboratory for Developmental Genes and Human Disease Ministry of EducationInstitute of Life SciencesSoutheast UniversityNanjing 210096China Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNanjing 226001China Institute for Stem Cell and Neural Regeneration State Key Laboratory of Reproductive MedicineSchool of PharmacyNanjing Medical UniversityNanjing 211166China

Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site,orchestrate the differentiation process, and promote the integration of neural circuitry for functional *** these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.

关键词： Stem cell Rehabilitation Neuromodulation Transcranial magnetic stimulation Transcranial direct current stimulation Deep brain stimulation

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Recent progress in drug delivery

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1145-1162页

作者： Chong Li Jiancheng wang Yiguang wang Huile Gao Gang Wei Yongzhuo Huang Haijun Yu Yong Gan yongjun wang Lin Mei Huabing Chen Haiyan Hu Zhiping Zhang Yiguang Jin College of Pharmaceutical Sciences Southwest UniversityChongqing 400715China Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China Key Laboratory of Smart Drug Delivery Ministry of EducationFudan UniversityShanghai 201203China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmaceutical Sciences(Shenzhen) Sun Yat-sen UniversityGuangzhou 510275China School of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Drug delivery systems(DDS)are defined as methods by which drugs are delivered to desired tissues,organs,cells and subcellular organs for drug release and absorption through a variety of drug *** usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility,drug aggregation,low bioavailability,poor biodistribution,lack of selectivity,or to reduce the side effects of therapeutic *** 2015-2018,significant progress in the research on drug delivery systems has been achieved along with advances in related fields,such as pharmaceutical sciences,material sciences and biomedical *** review provides a conciseoverview of current progress in this research area through its focus on the delivery strategies,construction techniques and specific *** is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.

关键词： Pharmaceutics Drug delivery system Basic research Application Delivery strategy

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