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GSH-Sensitive Pt（Ⅳ） Prodrug-Loaded Phase-Transitional Nanoparticles with A Hybrid Lipid-Polymer Shell for Precise Theranostics against Ovarian Cancer

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GSH-Sensitive Pt（Ⅳ） Prodrug-Loaded Phase-Transitional Nan...

2018年第十二届中国药物制剂大会

作者： Hui Huang Yang Dong Yanhua Zhang Dan Ru Zhihua Wu Jiali Zhang Ming Shen 孙颖 Yourong Duan State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Renji Hospital School of Medicine Shanghai Jiao Tong University

Platinum（Ⅱ）-based anticancer drugs dominate the chemotherapy field of ovarian cancer. However, the patient’s quality of life has severely limited owing to dose-limiting toxicities and the advanced disease at the time of diagnosis. New theranostic strategies to diagnose and overcome chemotherapy toxicities is highly desirable. Herein, multifunctional tumor-targeted nanosized ultrasound contrast agents（GSH-sensitive Pt（Ⅳ） prodrug-loaded phase-transitional nanoparticles, Pt（Ⅳ） NP-cRGD） are developed for precise theranostics against ovarian cancer. Pt（Ⅳ） NP-cRGD are composed of a perfluorohexane liquid core, a hybrid lipidpolymer shell with PLGA12 k-PEG2 k and DSPE-PEG1 k-Pt（Ⅳ）, and an active targeting ligand, the cRGD peptide. Pt（Ⅳ）, a popular alternative to cisplatin, was covalently attached to DSPE-PEG1 k to form the prodrug, which fine-tuned lipophilicity and improved cellular uptake. Pt（Ⅳ） NP-cRGD exhibited strong echogenic signals and excellent echo persistence under an US field. In addition, the GSH-sensitive and UStriggered drug delivery system maximized the therapeutic effect while reducing the toxicity of chemotherapy. The mechanistic studies confirmed that Pt（Ⅳ） NP-cRGD with US consumed glutathione and enhanced ROS levels, which further causes mitochondria-mediated apoptosis. Thus, the nanosized UCAs in this work may provide a useful insight into the development of various multifunctional UCAs for precise theranostics against various cancers.

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Analysis of Adaptation Process of Evidence-Based Interventions by Taking Post-Stroke Dysphagia Screening As an Example--Based on a Series of Empirical studies

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Journal of Integrative Nursing 2019年第3期1卷 123-131页

作者： Xiao-Yan ZHANG Jun-Qiang ZHAO Shang-Qian GAO Li-Jiao YAN Xue-Jing LI Jing-Ya MA Yu-Fang HAO School of Nursing Beijing University of Chinese MedicineBeijingChina Best Practice Spotlight Organization Beijing University of Chinese MedicineBeijingChina Collaborating Center of Joanna Briggs institute Beijing University of Chinese MedicineBeijingChina School of Nursing University of OttawaOttawaCanada Department of General Surgery Peking University First HospitalBeijing 100034China

Background:Evidence-based interventions(EBIs)are frequently adapted or modified during the implementation process to meet the needs of the target context,public health professionals,or health practitioners.However,little is known about how the EBIs of the same clinical problem at a different time(sustainability)and a different setting(scalability)should be adapted to facilitate implementation.To address this gap,this research aims to analyze the adaptations process of EBIs by taking post-stroke dysphagia screening as an example based on a series of empirical studies.Methods:We reviewed three best practice implementation projects of post-stroke dysphagia identification and management in China's Mainland,and conducted a comparative analysis of three projects of dysphagia screening practical decision-making according to core elements of evidence-based nursing(EBN).Results:We identified the core elements of EBN that influence decision-making in each best practice implementation project.The decision-making of screening time and tool for dysphagia in the three projects varied.Project 1:Post-stroke dysphagia was screened using Water Swallow Test(WST)before the first intake of liquid or food.Project 2:A sustainability study based on project 1,post-stroke dysphagia was screened using Standardized Swallowing Assessment(SSA)before the first intake of liquid or food,within 24 hours of admission.Project 3:A community scalability study based on project 2,post-stroke dysphagia was screened using Water Swallow Test(WST)before the first intake of liquid or food,within 24 hours after referral.Conclusions:Adaption of EBIs needs to fully consider the best available external evidence from systematic research,clinical expertise,patient preferences,as well as context.

关键词： Adaptation Evidence-based nursing Stroke Dysphagia Screen Implementation

Computational studies on second-order nonlinear optical properties of solid-state materials

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Computational studies on second-order nonlinear optical prop...

中国化学会第十二届全国量子化学会议

作者： Zuju MA Kechen WU State Key Laboratory of Structural Chemistry Laboratory of Theoretical and Computational ChemistryFujian Institute of Research on the Structure of MatterChinese Academy of Sciences

The solid-state nonlinear optical（NLO）materials play critical roles in the extension of laser frequencies tunnable through unltravoilet to infrared spectroscopic regions.In the past decades,the development of NLO materials has made great progress,but it is still a challenge to develop novel solid-state materials with significant NLO properties particularly applied in mid-to-far infrared region.We present the recent advances in the computational studies on the second-order NLO properties of solid-state materials within the first principle DFT framework.The studies revealed some potential NLO materials:（1）the strain-induced improvements of second-order NLO response of strontium tetraborate crystal opening a new way to exploring NLO crystals;（2）simulations of LO and NLO properties of mercury iodate crystal predicting its applications in IR region;（3）evolutions of the structure-NLO property relationship of the multifunctional NLO material Na As Se2crystal.The computational study using quantum chemical approximations such as DFT methods now becomes an important tool to accelerate the discovery of advanced NLO solid-state materials.Our presented results showed the efforts along this way.

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Bone cancer-induced hypersensitivity is not necessarily correlated with spinal microglial CX3CR1 overexpression in mice

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Bone cancer-induced hypersensitivity is not necessarily corr...

中国神经科学学会第十二届全国学术会议

作者： Xin Zhao Huizhu Liu Benlong Liu Hui Li Ning Lü Yu-Qiu Zhang institute of Neurobiology Institutes of Brain Science State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science Fudan University

Objective Bone cancer pain is one of the most severe symptoms in cancer patients. Previous studies have suggested that spinal microglia activation is necessary for the development of inflammatory and neuropathic pain. Our recent study showed that spinal microglial activation contributed to the maintenance of advanced bone cancer pain in a rat model. However, there is a large variation in spinal microglial activation in bone cancer pain due to differences in species/strains and origins of tumor cells. CX3CR1, a sole receptor of chemokine CX3 CL1 in the central nervous system, specifically expressed in spinal microglia. CX3 CL1/CX3CR1 signaling plays a crucial role in pathological pain via neuron-microglia communication. The present study explored whether microglial CX3CR1 in the spinal dorsal horn is involved in bone cancer pain in a mouse model. Methods Bone cancer pain model was established by injecting Lewis lung carcinoma cells into the tibia in mice. By means of immunohistochemistry and western blotting, the expression level of CX3CR1, fractalkine, GFAP and Iba1（marker of microglia） was detected. Results（1） Significant mechanical allodynia and thermal hyperalgesia developed in 14 d and persisted for at least 28 d in the ipsilateral hindpaw to tumorburned limb in both wide type mice and CX3CR1 knockout mice following Lewis lung carcinoma cells inoculation.（2）Spinal CX3CR1 and Iba-1（a marker of microglia） expression did not change during 7-28 days after tumor inoculation, while the expression level of GFAP gradually increased.（3）Intrathecal injection of a neutralizing antibody against CX3CR1 did not attenuate established hypersensitivity on wide type mice on day 21 post-tumor. Conclusion These results suggests that unlike in inflammatory and neuropathic pain, as well as in rat bone cancer pain, mice CX3CR1 in spinal microglia may be not involved in bone cancer pain.

关键词： Microglia CX3CR1 Fractalkine Bone Cancer Pain

Molecular Analyses of Early-Onset Gastric Cancer in Brazilian Patients: <i>TP</i>53 Mutations, Cadherin-Catenin and Mucins Proteins Expression

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Journal of Cancer Therapy 2013年第1期4卷 33-42页

作者： Edaise Maria da Silva J. H. T. G. Fregnani Ghyslaine Martel Wilson Luiz Costa Jr. Felipe José Fernández Coimbra Maria Isabel Waddington Achatz Pierre Hainaut Fernando Augusto Soares Department of Anatomic Pathology Hospital AC Camargo Sao Paulo Brazil Research and Teaching institute Barretos Cancer Hospital Barretos Brazil International Agency for Research on Cancer Molecular Carcinogenesis Group Lyon France Department of Abdominal Surgery Hospital AC Camargo Sao Paulo Brazil Department of Oncogenetics Hospital AC Camargo Sao Paulo Brazil.

Early gastric carcinomas may develop with a molecular profile differing from sporadic carcinomas occurring at a later age. In this study, we analyzed a retrospective series of 88 patients with gastric adenocarcinoma diagnosed before the age of 45 years for the presence of TP53 mutations, clinicopathological features and immunohistochemistry to evaluate the expression of markers considered to be important in gastric carcinogenesis (E-cadherin, β-catenin, MUC1, MUC2, MUC5AC, MUC6 and p53). The majority of proportion of tumors were diffuse-type (70%) and advanced stage (56%). Familial history of cancer was positive in 21% of the cases. There was a significant association between altered expression of E-cadherin and β-catenin, and between p53 expression and perineural invasion. TP53 mutations were detected in 14.5% of evaluated cases, including a germline mutation (p.R337H) in a 12-year old patient. Overall survival analysis showed significant differences in relation with tumor stage and histopathology. The evaluated biomarkers did not present prognostic value in non-exploratory multivariate analyses. The low frequency of TP53 mutations in this series suggests these alterations are not a major molecular event in gastric cancer occurring at early age, although the identification of a case with germline p.R337H mutation is consistent with the hypothesis that a small proportion of early, apparently sporadic gastric cancer, may be associated with widespread Brazilian founder mutations. Further studies are needed to evaluate the prognostic significance of markers for specific groups of patients according to tumor histology and familial history.

关键词： Early-Onset Gastric Cancer Young Patients Cellular Adhesion TP53 Mutations

Association of Elevated Yes-Associated Protein Expression with Gastric Cancer and Its Clinicopathological Features: A Meta-Analysis

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Journal of Biosciences and Medicines 2020年第2期8卷 96-109页

作者： Qian Peng Ting Yuan Xingmei Duan Jianyou Shi Lan Bai Jiying Yu Lei Zhong Radiation Oncology Key Laboratory of Sichuan Province Sichuan Cancer Hospital & Institute Sichuan Cancer Center School of Medicine University of Electronic Science and Technology of China Chengdu China Personalized Drug Therapy Key Laboratory of Sichuan Province Department of Pharmacy Sichuan Provincial People’s Hospital School of Medicine University of Electronic Science and Technology of China Chengdu China

Objectives: To evaluate the difference of YAP-positive expression between GC and adjacent tissues, as well as the association of elevated YAP expression with clinicopathological features of GC. Methods: PubMed, Embase, Web of Science databases and the Chinese National Knowledge Infrastructure (CNKI) were searched from inception up to December 2018. The pooled ORs and corresponding 95% CIs were used to assess the strength of association. The heterogeneity among eligible studies was evaluated by the Q-test and I2 values. The sensitivity analysis was performed by sequential omission of individual studies. Moreover, Begg’s test and Egger’s test were used to evaluate publication bias. Results: A total of 2229 patients from 16 studies were included in this meta-analysis. The results showed that positive YAP expression was closely correlated with GC but not adjacent non-tumor tissue (OR = 8.08, 95% CI = 4.41 - 14.80). Additionally, YAP overexpression was found to be associated with more advanced TNM stage (OR = 2.68, 95% CI = 1.61 - 4.48), deeper invasion depth (OR = 2.05, 95% CI = 1.32 - 3.19), and lymph node metastasis (OR = 1.95, 95% CI = 1.29 - 2.96). No significant correlation was observed between YAP overexpression and degree of differentiation (OR = 1.17, 95% CI = 0.63 - 2.16), as well as gender of patients (OR = 1.12, 95% CI = 0.91 - 1.37) or tumor size (OR = 1.11, 95% CI = 0.82 - 1.49) of gastric cancer. Conclusions: This meta-analysis demonstrated that YAP might be a promising diagnostic marker and even a therapeutic target for gastric cancer.

关键词： Yes-Associated Protein Gastric Cancer Clinicopathological Feature Meta-Analysis

Biocompatible organic dots with aggregation-induced emission for in vitro and in vivo fluorescence imaging

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中国科学：化学 2013年第9期43卷 1211-1211页

作者： LI Kai DING Dan ZHAO QiuLi SUN JingZhi TANG Ben Zhong LIU Bin institute of Materials Research and Engineering 3 Research Link Singapore 117602 Department of Chemical and Biomolecular Engineering National University of Singapore 4 Engineering Drive 4 Singapore 117576 Singapore MOE Key Laboratory of Macromolecule Synthesis & Functionalization Institute of Biomedical Macromolecules Department of Polymer Science & Engineering Zhejiang University Hangzhou 310027 China Department of Chemistry The Hong Kong University of Science & Technology Clear Water Bay Kowloon Hong Kong China SCUT-HKUST Joint Research Laboratory State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 China

Fluorescent probes play a key role in modern biomedical research.As compared to inorganic quantum dots(QDs)composed with heavy metal elements,organic dye-based fluorescent nanoparticles have higher biocompatibility and are richer in variety.However,traditional organic fluorophores tend to quench fluorescence upon aggregation,which is known as aggregation-caused quenching(ACQ)effect that hinders the fabrication of highly emissive fluorescent nanoparticles.In this work,we demonstrate the synthesis of organic fluorescent dots with aggregation-induced emission(AIE)in far-red/near-infrared(FA/NIR)region.A conventional ACQ-characteristic fluorescent dye,3,4:9,10-tetracarboxylic perylene bisimide(PBI),is converted into an AIE fluorogen through attaching two tetraphenylethylene(TPE)moieties.The fluorescent dots with surface folic acid groups are fabricated from PBI derivative(DTPEPBI),showing specific targeting effect to folate receptor-overexpressed cancer cells.In vivo studies also suggest that the folic acid-functionalized AIE dots preferentially accumulate in the tumor site through enhanced permeability and retention(EPR)effect and folate receptor-mediated active targeting effect.The low cytotoxicity,good FR/NIR contrast and excellent targeting ability in in vitro/in vivo imaging indicate that the AIE dots have great potentials in advanced bioimaging applications.

关键词：荧光成像生物相容性生物医学发光点光聚集体内体外诱导

Stress Corrosion Cracking （SCC） of Nickel-base Weld Metals in PWR Primary Water

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Stress Corrosion Cracking （SCC） of Nickel-base Weld Metals...

中国材料大会2012

作者： Ru Xiong Yingjie Qiao Guiliang Liu School of Materials Science and Chemical Engineering Harbin Engineering University National Key Laboratory of Reactor Fuel and Materials Nuclear Power Institute of China

ISBN: (纸本)9783037856086;3037856084

This discussion reviewed the occurrence of stress corrosion cracking （SCC） of alloys 182 and 82 weld metals in primary water （PWSCC） of pressurized water reactors （PWR） from both operating plants and laboratory experiments. Results from in-service experience showed that more than 340 Alloy 182/82 welds have sustained PWSCC. Most of these cases have been attributed to the presence of high residual stresses produced during the manufacture aside from the inherent tendency for Alloy 182/82 to sustain SCC. The affected welds were not subjected to a stress relief heat treatment with adjacent low alloy steel components. Results from laboratory studies indicated that time-to-cracking of Alloy 82 was a factor of 4 to 10 longer than that for Alloy 182. PWSCC depended strongly on the surface condition, surface residual stresses and surface cold work, which were consistent with the results of in-service failures. Improvements in the resistance of advanced weld metals, Alloys 152 and 52, to PWSCC were discussed.

关键词： Alloy 182 and 82 Alloy 152 and 52 PWSCC Residual stress Cold-work

Optical source profiles of brown carbon in size-resolved particulate matter from biomass burning over Guanzhong Plain,China

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Optical source profiles of brown carbon in size-resolved par...

第十五届海峡两岸气胶技术研讨会

作者： Yali Lei Zhenxing Shen Department of Environmental Science and Engineering Xi'an Jiaotong University Key Lab of Aerosol Chemistry & Physics Institute of Earth EnvironmentChinese Academy of Sciences

Emissions from biomass burning can be significant contributors to brown carbon(Br C).Biomass burning samples for both PM samples and size-resolved samples were collected from maize straw smoldering in the "Heated Kang" and maize-straw briquette in an advanced stove.Optical properties of brown carbon(Br C) for both water soluble extracts and methanol soluble extracts were determined with UV-vis spectrometer,including light absorption coefficient(babs),absorption ? ngstr?m exponent(AAE),and mass absorption cross-section(MAC).Carbonaceous aerosol species,including organic carbon(OC),element carbon(EC),eight carbon fractions as well as water soluble potassium(K+) were also measured.AAE and MAC365 values of the methanol extracts for smoldering burning in the "Heated Kang" were 6.66(300-500 nm) and 1.77 m g.AAE and MAC365 values for methanol extracts from straw briquettes burning in an advanced stove were 5.9 ± 0.6 and 1.28 ± 0.32 m g,respectively.Size distributions for babs365,MAC365,and water soluble K from all biomass burning samples displayed a unimodal size distribution,peaking at the size advanced stove,the values for(advanced stove was that the proportions of MAC365 values for the size range of studies(0.30 m g for 1 kgh and 0.28 m g for 1 kgh) were much higher than those from briquette burning(0.18 m g for 1 kgh and 0.15 m g for 1.2 kgh).Methanol extracts absorbs more than water extracts for all size ranges and wavelengths.The results highlighted that the burning straw briquettes burning in ad

关键词： biomass burning maize straw size-resolved BrC light absorption coefficient