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Chinese Journal of Integrative Medicine 2022年第7期28卷 579-585页

作者： DENG Bo JIA Li-qun WAN Dong-gui WANG Bao-yi CHENG Zhi-qiang DENG Chao Center of Science and Technology China-Japan Friendship HospitalBeijing 100029China Integrative Oncology Department of Chinese Medicine and Western Medicine China-Japan Friendship HospitalBeijing 100029China

Objective: To evaluate the efficacy of Wen-Luo-Tong Granules(WLT) local administration in the treatment of patients with peripheral neuropathy(PN) induced by chemotherapy or target therapy. Methods: This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT(39 cases) and control groups(39 cases) using a block randomization method. The WLT group received WLT(hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events(NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life QuestionnaireChemotherapy Induced Peripheral Neuropathy(QLQ-CIPN20), and Quality of Life Questionnaire-Core30(QLQ-C30). Results: After treatment, the PN grade in the WLT group was significantly lower than that in the control group(1.00±0.29 vs. 1.75±0.68, Ptherapy or target therapy.(Trial registration No. ChiCTR1900023862)

关键词： peripheral neuropathy chemotherapy target therapy Chinese medicine Wen-Luo-Tong randomized controlled trial

Advance in metabolism and target therapy in breast cancer stem cells

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World Journal of Stem Cells 2020年第11期12卷 1295-1306页

作者： Xu Gao Qiong-Zhu Dong Department of Breast Surgery Yiwu Maternity and Children HospitalYiwu 322000Zhejiang ProvinceChina Department of General Surgery Cancer Metastasis InstituteInstitutes of Biomedical SciencesHuashan HospitalFudan UniversityShanghai 200032China

Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell *** studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these ***-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional ***,the metabolic properties of cancer cells differ markedly from those of normal *** efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer *** targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer ***,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.

关键词： Breast cancer Cancer stem cells Metabolism Oxidative phosphorylation Tumor relapse target therapy

Progress in target therapy of advanced non-small cell lung cancer

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Drug Combination therapy 2021年第4期3卷 5-10页

作者： Li Zhang Rui Cao Department of Medical Oncology Konggang HospitalTianjin Medical University Cancer Institute&HospitalTianjin300308China

Lung cancer is one of the most common malignant tumors,and its morbidity and mortality are relatively *** for small cell lung cancer(SCLC),the mortality rate is between 80-90%.Unfortunately,more than 50%of lung cancer patients are diagnosed at an advanced *** traditional treatment for advanced non-small cell lung cancer(NSCLC)is *** recent years,with the rapid development of molecular pathology,we have a deeper understanding of the underlying pathological mechanism and heterogeneity of lung cancer,especially *** targeted therapy is more accurate because of its anti-tumor effect,and the incidence of adverse drug reactions is *** with chemotherapy in the traditional sense,the degree of damage to normal tissues is also significantly ***,it has become a research hotspot in recent *** article reviews the research progress of various molecular targeted drugs for the treatment of lung cancer based on domestic and foreign research literature and related data.

关键词： NSCLC target therapy targeted drugs Mutant gene

Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma

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Frontiers of Medicine 2016年第1期10卷 52-60页

作者： Zhi Xu Chunxiang Cao Haiyan Xia Shujing Shi Lingzhi Hong Xiaowei Wei Dongying Gu Jianmin Bian Zijun Liu Wenbin Huang Yixin Zhang Song He Nikki Pui-Yue Lee Jinfei Chen Department of Oncology Nanjing First Hospital Nanjing Medical University Nanjing 210006 China Department of General Surgery Nanjing First Hospital Nanjing Medical University Nanjing 210006 China Department of Pathology Nanjing First Hospital Nanjing Medical University Nanjing 210006 China Department of General Surgery Nantong Tumor Hospital Nantong 226361 China Department of Pathology Nantong Tumor Hospital Nantong 226361 China Department of Surgery Faculty of Medicine The University of Hong Kong Hong Kong China

Hepatocellular carcinoma （HCC） is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 16 （PPM1D） was highly expressed in the majority of HCC cases （approximately 59%） and significantly associated with high serum a-fetoprotein （AFP） level （P = 0.044）. Kaplan- Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCC- specific overall survival （HR, 2.799; 95% CI, 1.346-5.818, P = 0.006）. Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC.

关键词： PPM1D hepatocellular carcinoma prognosis target therapy

Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第15期20卷 4128-4140页

作者： Bhavna Rani Yuan Cao Andrea Malfettone Ciprian Tomuleasa Isabel Fabregat Gianluigi Giannelli Department of Medical Biosciences and Human Oncology Padiglione Semeiotica Medica70124 BariItaly Bellvitge Biomedical Research Institute (IDIBELL) 08028 BarcelonaSpain Department of Hematology Center for Genomics and Translational MedicineIuliu Hatieganu University of Medicine and Pharmacy400012 Cluj NapocaRomania Department of Physiological Sciences Ⅱ University of Barcelona08028 BarcelonaSpain

Hepatocellular carcinoma is difficult to treat,primarilybecause the underlying molecular mechanisms drivingclinical outcome are still poorly *** suggests that the tissue microenvironmenthas a role in the biological behavior of the *** clinical issue is to identify the best target fortherapeutic ***,we discuss the hypothesis that the entire tissue microenvironment might beconsidered as a biological ***,the tissuemicroenvironment consists of several cellular and biochemical components,each of which displays a distinctbiological *** discuss the major components ofthis environment and consider how they may interactto promote tumor/host crosstalk.

关键词： Tissue microenvironment Hepatocellular carcinoma Transforming growth factor-beta Laminin-5 Cancer stem cells therapy target therapy

Bone/cartilage targeted hydrogel: Strategies and applications

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Bioactive Materials 2023年第5期23卷 156-169页

作者： Hao Zhang Shunli Wu Weikai Chen Yan Hu Zhen Geng Jiacan Su Institute of Translational Medicine Shanghai UniversityShanghai200444China Musculoskeletal Organoid Research Center Shanghai UniversityShanghai200444China School of Medicine Shanghai UniversityShanghai200444China School of Environmental and Chemical Engineering Shanghai UniversityShanghai200444China

The skeletal system is responsible for weight-bearing,organ protection,and *** diseases caused by trauma,infection,and aging can seriously affect a patient’s quality of *** targeted biomaterials are suitable for the treatment of bone *** with bone-targeted properties can improve drug utilization and reduce side effects.A large number of bone-targeted micro-nano materials have been ***,only a few studies addressed bone-targeted *** large size of hydrogel makes it difficult to achieve systematic ***,local targeted hydrogel still has significant *** in bone/cartilage extracellular matrix and bone cells provide binding sites for bone-targeted *** delivery systems featuring microgels with targeting properties is a key construction strategy for bone-targeted ***,injectable hydrogel drug depot carrying bone-targeted drugs is another *** this review,we summarize the bone-targeted hydrogel through application environment,construction strategies and disease *** hope this article will provide a reference for the development of bone-targeted *** also hope this article could increase awareness of bone-targeted materials.

关键词： Bone Cartilage Hydrogel target therapy Bone disease

The crucial roles of m^(6)A RNA modifications in cutaneous cancers:Implications in pathogenesis,metastasis,drug resistance,and targeted therapies

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Genes & Diseases 2023年第6期10卷 2320-2330页

作者： Cong Huang Kaoyuan Zhang Yang Guo Changbing Shen Xiaoming Liu Haiyan Huang Xia Dou Bo Yu Department of Dermatology Skin Research Institute of Peking University Shenzhen HospitalPeking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China Department of Dermatology Skin Research Institute of Peking University Shenzhen HospitalPeking University Shenzhen HospitalShenzhenGuangdong 518036China

N6-methyladenosine(m^(6)A)is the most abundant internal modification on *** is a dynamical and reversible process,which is regulated by m^(6)A methyltransferase and m^(6)A *** m^(6)A modified RNA can be specifically recognized by the m^(6)A reader,leading to RNA splicing,maturation,degradation or *** abnormality of m^(6)A RNA modification is closely related to a variety of biological processes,especially the occurrence and development of *** studies have shown that m^(6)A RNA modification is involved in the pathogenesis of skin ***,the precise molecular mechanisms of m^(6)A-mediated cutaneous tumorigenesis have not been fully ***,this review will summarize the biological characteristics of m^(6)A modification,its regulatory role and mechanism in skin cancers,and the recent research progress of m^(6)A-related molecular drugs,aiming to provide new ideas for clinical diagnosis and targeted therapy of cutaneous cancers.

关键词： Cutaneous squamous cell carcinoma Cutaneous melanoma m6A modification m^(6)A-related drugs target therapy

Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3410-3426页

作者： Honglin Tang Yanan Xue Bowen Li Xiaojie Xu Fu Zhang Jiajing Guo Qijun Li Tingting Yuan Yuan Chen Yubin Pan Yuan Ping Da Li Department of Medical Oncology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310058China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang UniversityHangzhou 310003China

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine(GEM) with the molecular-targeted drug erlotinib(Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuliresponsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA(siRNA) for synergistic pancreatic cancer treatment. This “all-in-one”delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor(PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

关键词： Chemotherapy target therapy siRNA Nanomedicine Hybrid membrane Drug antagonism Pancreatic carcinoma Patient-derived tumor

B cells biology in systemic lupus erythematosus—from bench to bedside

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Science China(Life Sciences) 2015年第11期58卷 1111-1125页

作者： ZHAO LiDan YE YanXia ZHANG Xuan Department of Rheumatology & Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Systemic lupus erythematosus(SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE. In this article, mechanisms of self-tolerance loss of B cells and promising B cell-targeting therapies in lupus are reviewed and discussed.

关键词： systemic lupus erythematosus B cell pathogenesis target therapy

Recent advances in targeted stimuli-responsive nano-based drug delivery systems combating atherosclerosis

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Chinese Chemical Letters 2022年第4期33卷 1705-1717页

作者： Yilin Song Huaqing Jing Long Binh Vong Jinping Wang Nan Li Tianjin Key Laboratory of Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China Key Laboratory of Molecular Biophysics of Hebei Province Institute of BiophysicsSchool of SciencesHebei University of TechnologyTianjin 300401China School of Biomedical Engineering International UniversityHo Chi Minh 700000Vietnam Vietnam National University Ho Chi Minh City(VNU-HCMC) Ho Chi Minh 700000Vietnam

Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, the development of carriers precisely delivering the therapeutic agents to the target sites is the primary goal, which could minimize the potential adverse effects and be more effective in treating lesions. Due to the precise location, real-time monitoring, AS microenvironment response, and low toxicity, stimuli-responsive nano-based drug delivery systems(NDDSs) have been a promising approach in AS treatments. Herein, we will systematically summarize the recent advances in stimuli-responsive NDDSs for AS treatment, including internal stimuli(reactive oxygen species, enzyme, shear stress, and pH) and external stimuli(light, ultrasound, and magnetism) responsive NDDSs. Besides, we will also summarize in detail the classification of stimuli-responsive NDDSs for AS, such as organic NDDSs(e.g., lipid-based and polymer-based nanomaterials), inorganic NDDSs(e.g., metal-based nanoparticles and nonmetallic nanomaterials), and composite multifunctional NDDSs. Finally, the critical challenges and prospects of this field will also be proposed and discussed.

关键词： Atherosclerosis stimuli-responsive Nano-based drug delivery systems Theranostics target therapy