Advanced Therapeutics最新文献_第9页

Controlled Delivery of Paclitaxel via Stable Synthetic Protein Nanoparticles 通过稳定的合成蛋白纳米颗粒控制紫杉醇的输送

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-27 DOI: 10.1002/adtp.202400208

Ava Mauser, Isabel Waibel, Kaushik Banerjee, Anzar A. Mujeeb, Jingyao Gan, Sophia Lee, William Brown, Nigel Lang, Jason Gregory, Jeffery Raymond, Matthias Franzeb, Anna Schwendeman, Maria G. Castro, Joerg Lahann

{"title":"Controlled Delivery of Paclitaxel via Stable Synthetic Protein Nanoparticles","authors":"Ava Mauser, Isabel Waibel, Kaushik Banerjee, Anzar A. Mujeeb, Jingyao Gan, Sophia Lee, William Brown, Nigel Lang, Jason Gregory, Jeffery Raymond, Matthias Franzeb, Anna Schwendeman, Maria G. Castro, Joerg Lahann","doi":"10.1002/adtp.202400208","DOIUrl":"10.1002/adtp.202400208","url":null,"abstract":"Despite decades of intense research, glioma remains a disease for which no adequate clinical treatment exists. Given the ongoing therapeutic failures of conventional treatment approaches, nanomedicine may offer alternative options because it can increase the bioavailability of drugs and alter their pharmacokinetics. Here, a new type of synthetic protein nanoparticles (SPNPs) is reported that allow for effective loading and controlled release of the potent cancer drug, paclitaxel (PTX) – a drug that so far has been unsuccessful in glioma treatment due to hydrophobicity, low solubility, and associated delivery challenges. SPNPs are prepared by electrohydrodynamic (EHD) jetting of dilute solutions of PTX-loaded albumin made by high-pressure homogenization. After EHD jetting, PTX SPNPs possess a dry diameter of 165 ± 44 nm, hydrated diameter of 297 ± 102 nm, and a zeta potential of −19 ± 8 mV in water. For the SPNP formulation with a total PTX loading of 9.4%, the loading efficiency is 94%, and controlled release of PTX is observed over two weeks (6% burst release). PTX SPNPs are more potent (68% lethality) than free PTX (45% lethality using 0.2% dimethyl sulfoxide). PTX SPNPs in combination with IR show a significant survival benefit in glioma-bearing mouse models, avoid adverse liver toxicity, and maintain a normal brain architecture. Immunohistochemistry reveals a dramatic tumor size reduction including 40% long-term survivors without discernible signs of tumor. Using flexibly engineered SPNPs, this work outlines an efficient strategy for the delivery of hydrophobic drugs that are otherwise notoriously hard to deliver.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 11","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202400208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced Precision Immunotherapy of Colorectal Cancer through Chemo-Photothermal Nanoparticles via Endoplasmic Reticulum Stress Mediated Apoptotic Pathways 通过内质网应激介导的凋亡途径，化疗-光热纳米粒子增强结直肠癌的精准免疫疗法

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-27 DOI: 10.1002/adtp.202400045

Shanshan Wang, Zhiqiang Bi, Tianming Lu, Ruoning Qian, Jie Yu, Qiang Zhang, Hao Yang, Wenli Lu, Yuanyuan Guo, Xiaoqing Xin, Yong Bian, Ruogu Qi

{"title":"Enhanced Precision Immunotherapy of Colorectal Cancer through Chemo-Photothermal Nanoparticles via Endoplasmic Reticulum Stress Mediated Apoptotic Pathways","authors":"Shanshan Wang, Zhiqiang Bi, Tianming Lu, Ruoning Qian, Jie Yu, Qiang Zhang, Hao Yang, Wenli Lu, Yuanyuan Guo, Xiaoqing Xin, Yong Bian, Ruogu Qi","doi":"10.1002/adtp.202400045","DOIUrl":"10.1002/adtp.202400045","url":null,"abstract":"Colorectal cancer (CRC) stands out as one of the most prevalent gastrointestinal cancers. Current treatment strategies for CRC are significantly hindered by systemic toxicity and suboptimal therapeutic efficacy. This study aims to overcome these limitations by developing a robust tumor-targeting chemo-photothermal strategy, combining Bortezomib (BTZ) as a proteasome inhibitor, IR780 iodide as a near-infrared dye, and Photothermal Therapy (PTT) agent, with hyaluronic acid (HA) serving as the shell for tumor targeting, denoted as HA/PB@IR780. The investigations reveal the impressive tumor-targeting affinity of HA/PB@IR780, leading to a synergistic chemo-photothermal therapeutic effect both in vitro and in vivo. Additionally, this material demonstrates the capability for drug release triggered by low pH conditions. Moreover, HA/PB@IR780 induced the generation of reactive oxygen species (ROS), triggered cells apoptosis via the PERK-CHOP-Bcl-2 pathway, and induced Immunogenic Cell Death (ICD) in CT26 cells. Importantly, HA/PB@IR780 selectively targets tumor sites, mitigating systemic toxic side effects and significantly extending the survival of CT26 tumor-bearing mice. In conclusion, this designed tumor-targeting nanocarrier represents a promising and potentially effective platform for the precise treatment of CRC.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141502647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LTBP2 Knockdown Ameliorates Cardiac Fibrosis and Apoptosis via Attenuating NF-κB Signaling Pathway and Oxidative Stress in Mice with Cardiac Hypertrophy 敲除 LTBP2 可通过减轻 NF-κB 信号通路和氧化应激改善心肌肥厚小鼠的心肌纤维化和细胞凋亡

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-26 DOI: 10.1002/adtp.202300451

Yifeng Wang, Dongxu Hua, Kun Zhao, Qiyang Xie, Xiaoguang Wu, Min Gao, Wanling Huang, Wen Huang, Peng Li, Yanhui Sheng

{"title":"LTBP2 Knockdown Ameliorates Cardiac Fibrosis and Apoptosis via Attenuating NF-κB Signaling Pathway and Oxidative Stress in Mice with Cardiac Hypertrophy","authors":"Yifeng Wang, Dongxu Hua, Kun Zhao, Qiyang Xie, Xiaoguang Wu, Min Gao, Wanling Huang, Wen Huang, Peng Li, Yanhui Sheng","doi":"10.1002/adtp.202300451","DOIUrl":"10.1002/adtp.202300451","url":null,"abstract":"At present, there is no therapeutic approach available to reverse the progression of pathological fibrosis and ventricle chamber stiffening. This study is designed to explore the effects of latent transforming growth factor-beta-binding protein 2 (LTBP2) on cardiac fibrosis in hypertrophic cardiomyopathy and the underlying mechanisms. The key differential gene LTBP2 is identified by mRNA sequencing. Ang II-induced cells and mice are treated with LTBP2 si-RNA or knockdown adenovirus, respectively, and the indicators of cardiac function, oxidative stress, cardiac fibrosis, apoptosis, and remodeling are examined. The underlying mechanism is elucidated in vitro by oxidative stress and an agonist of nuclear factor-kappa B (NF-κB). LTBP2 is upregulated in the cardiac tissue of mice with Ang II-mediated HF. The knockdown of LTBP2 enhanced cardiac function, attenuated cardiac fibrosis, apoptosis, hypertrophy, and oxidative stress injury, and suppressed NF-κB expression. These results are validated in vitro. The effects of LTBP2 gene silencing are reversed by either NF-κB or oxidative stress agonists in vitro. Taken together, these findings suggest that LTBP2 knockdown alleviates HF by inhibiting cardiac fibrosis, apoptosis, and hypertrophy via attenuating NF-κB signaling pathway and oxidative stress. Thus, targeting LTBP2 may be a novel approach to the treatment of HF.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141502704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Doxofylline: Advancing and Empowering Equitable Asthma and COPD Management Beyond Tradition 多索茶碱：超越传统，促进并增强哮喘和慢性阻塞性肺病的公平管理

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-26 DOI: 10.1002/adtp.202400103

Mario Cazzola, Clive P. Page, Luigino Calzetta, Paola Rogliani, Maria Gabriella Matera

引用次数: 0

Latest Progress on Tuberculosis and HIV Co‐Infection: A Closer Look at People of Different Ages 结核病和艾滋病病毒双重感染的最新进展：不同年龄段人群的近距离观察

IF 4.6 4区医学

Advanced Therapeutics Pub Date : 2024-06-26 DOI: 10.1002/adtp.202400033

Anna Yusuf Aliyu, Oluwatoyin A. Adeleke

引用次数: 0

Tumor Growth Inhibition and Induced the Immunogenic Death of Tumor Cells in Prostate Tumor Bone Metastases by Photothermal Therapy Mediated with Au Nanoparticles Modified with PDA 用 PDA 修饰的金纳米颗粒介导的光热疗法抑制前列腺肿瘤骨转移灶中肿瘤的生长并诱导肿瘤细胞的免疫性死亡

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-25 DOI: 10.1002/adtp.202300433

Ran Bin, Chen Zhu, Rao Yunjia, Yan Jin, Wang Jie, Xiao Dongqin, Lin Tao, Feng Gang

{"title":"Tumor Growth Inhibition and Induced the Immunogenic Death of Tumor Cells in Prostate Tumor Bone Metastases by Photothermal Therapy Mediated with Au Nanoparticles Modified with PDA","authors":"Ran Bin, Chen Zhu, Rao Yunjia, Yan Jin, Wang Jie, Xiao Dongqin, Lin Tao, Feng Gang","doi":"10.1002/adtp.202300433","DOIUrl":"10.1002/adtp.202300433","url":null,"abstract":"Upon progression to the metastatic stage, prostate tumors commonly exhibit multi-drug resistance. Combining multiple treatment protocols can be beneficial in overcoming this resistance, which is often attributed to tumor heterogeneity. Recently, nano-photosensitizer-mediated photothermal therapy is shown to inhibit tumor growth through multiple pathways, including thermal ablation and activation of the antitumor immune response. In this study, gold nanoparticles (Au) are selected as the core photosensitizer. Then, the photothermal conversion of Au is augmented through dopamine coating, and the chemotherapy drug doxorubicin (DOX) is grafted to the dopamine coating. The release of DOX from DOX-loaded dopamine-modified gold nanoparticles (Au@PDA@DOX) occurred in response to an acidic environment. The combination of chemotherapy and thermal ablation better inhibits the growth, migration, and invasion of tumor cells and induced tumor cell apoptosis and necrosis in vitro. More importantly, thermal ablation induces the immunogenic death of prostate tumor cells (RM-1) cells. The transition of prostate tumors from a “cold” to a “hot” tumor with immunogenicity is observed. The combination effectively activates the antitumor immune response, inhibits tumor growth, and alleviated bone damage by tumors in vivo. It is indicated that Au@PDA@DOX nanoparticles will offer a novel treatment protocol for prostate tumor bone metastases.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stability of Free and Liposomal Encapsulated RNA on a Mucoadhesive PVA Polymer for Esophageal RNA Drug Targeting Using the EsoCap System 利用 EsoCap 系统将游离和脂质体包裹的 RNA 稳定在具有黏附性的 PVA 聚合物上，实现食管 RNA 药物靶向治疗

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-25 DOI: 10.1002/adtp.202300446

Aileen Weide, Friederike Brokmann, Bettina Appel, Christoph Rosenbaum, Julius Krause, Una Janke, Mihaela Delcea, Werner Weitschies, Sabine Müller

{"title":"Stability of Free and Liposomal Encapsulated RNA on a Mucoadhesive PVA Polymer for Esophageal RNA Drug Targeting Using the EsoCap System","authors":"Aileen Weide, Friederike Brokmann, Bettina Appel, Christoph Rosenbaum, Julius Krause, Una Janke, Mihaela Delcea, Werner Weitschies, Sabine Müller","doi":"10.1002/adtp.202300446","DOIUrl":"10.1002/adtp.202300446","url":null,"abstract":"The development of RNA and oligonucleotide-based therapeutics is a longstanding goal and is currently gaining significant attention. Several RNA-based drugs are approved for clinical use. Others are under investigation or in preclinical trials. This study have initiated the development of RNA drugs for localized use in the esophagus, utilizing the EsoCap System. This system's core component is a mucoadhesive film that carries the RNA drug and is precisely applied to the esophagus. Research into the stability and properties of naked and liposomal-encapsulated RNA on mucoadhesive polymer film reveals that RNAs remain stable in various conditions without degradation, RNA leakage, or liposome fusion observed. The liposome size also remains constant after application on the film, drying, and rehydration. These findings pave the way for RNA drug development for esophageal diseases and their administration via the EsoCap system.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202300446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141502705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular Trafficking Pathway and ROS Scavenging Activity of Glycol Chitosan-Coated Cerium Oxide Nanoparticles in a Pathological AMD-Like Model 乙二醇壳聚糖包裹的氧化铈纳米粒子在病理型老年黄斑变性模型中的细胞内运输途径和 ROS 清除活性

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-20 DOI: 10.1002/adtp.202400030

Yong-Su Kwon, Zongchao Han

{"title":"Intracellular Trafficking Pathway and ROS Scavenging Activity of Glycol Chitosan-Coated Cerium Oxide Nanoparticles in a Pathological AMD-Like Model","authors":"Yong-Su Kwon, Zongchao Han","doi":"10.1002/adtp.202400030","DOIUrl":"10.1002/adtp.202400030","url":null,"abstract":"Age-related macular degeneration (AMD) is a degenerative eye disease that primarily affects the macula. AMD is a leading cause of vision loss in individuals over the age of 65, particularly more common in Caucasians than in other racial groups. Cerium oxide nanoparticles (CNPs) have emerged as highly promising nanomaterials in the treatment of AMD due to their potent antioxidant properties. In pathological damages of AMD conditions, characterized by oxidative stress resulting from an overproduction of reactive oxygen species (ROS), CNPs possess significant promise for attenuating the pathogenic processes and advancing therapeutic interventions. Despite their potential clinical applications, the widespread use of CNPs is greatly hampered by limited water solubility, and concerns have arisen about their potential impact on normal ROS production in mitochondria. Here, the antioxidative activity of glycol chitosan-coated CNPs (namely, GCCNPs) and their behavior in mouse primary RPE (mRPE) cells are reported through an in vitro trafficking study. This findings demonstrate that GCCNPs effectively neutralize excessive ROS and prefer to exclusively accumulate in cytosol without any uptake in the nucleus and mitochondria of the mRPE cells. Moreover, GCCNPs demonstrated therapeutic effects by reducing the ROS level in a laser-induced choroidal neovascularization (CNV) AMD-like murine model.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bacterial Influence on Pharmacokinetics of Tacrolimus and Sulfasalazine through Regulation of Host Metabolism 细菌通过调节宿主代谢影响他克莫司和磺胺沙拉嗪的药代动力学

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-20 DOI: 10.1002/adtp.202300449

David A. Cooper, Abhinav Bhushan

{"title":"Bacterial Influence on Pharmacokinetics of Tacrolimus and Sulfasalazine through Regulation of Host Metabolism","authors":"David A. Cooper, Abhinav Bhushan","doi":"10.1002/adtp.202300449","DOIUrl":"10.1002/adtp.202300449","url":null,"abstract":"The unpredictable oral bioavailability of established drugs like tacrolimus and sulfasalazine presents a significant clinical challenge. This variability can lead to either toxicity or insufficient therapeutic effect. It is known that alterations in drug transporters and metabolic enzymes influence drug bioavailability. Recent evidence suggests that the indirect metabolism by gut microbes could influence transporters and enzymes which can affect the bioavailability of oral drugs. In this study, the pharmacokinetics of tacrolimus and sulfasalazine are modeled under varying host colonic conditions induced by the bacteria E. coli Nissle 1917 and Bifidobacterium adolescentis. Insight is provided into the sensitivity of pharmacokinetics to the bacterial influence on expression of intestinal drug transporters and cytochrome p450 enzymes. Our findings demonstrate that bacterial modulation reduces tacrolimus peak blood concentration compared to healthy renal transplant patients. Conversely, bacterial presence leads to a two-fold increase in sulfasalazine's peak plasma concentration compared to healthy subjects. These results suggest that incorporating the gut bacteria's influence on colonic transporters and enzymes can improve the explanation of pharmacokinetic variability. This approach has the potential to refine pharmacokinetic models and ultimately address the challenge of variable oral drug bioavailability.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202300449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141502707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Urine Liquid Biopsies via Highly Integrated Digital PCR System for Accurate Detection of Bladder Cancer 通过高度集成的数字 PCR 系统进行尿液液体活检，准确检测膀胱癌

IF 3.7 4区医学

Advanced Therapeutics Pub Date : 2024-06-17 DOI: 10.1002/adtp.202400191

Yue Zhang, Ming Xu, Zhihong Wu, Fan Yang, Lu Zhang, Yiquan Liu, Jiahao Lv, Shuyue Xiang, Beiyuan Fan, Zijian Zhao, Yanzhao Li, Yang Yu

{"title":"Urine Liquid Biopsies via Highly Integrated Digital PCR System for Accurate Detection of Bladder Cancer","authors":"Yue Zhang, Ming Xu, Zhihong Wu, Fan Yang, Lu Zhang, Yiquan Liu, Jiahao Lv, Shuyue Xiang, Beiyuan Fan, Zijian Zhao, Yanzhao Li, Yang Yu","doi":"10.1002/adtp.202400191","DOIUrl":"10.1002/adtp.202400191","url":null,"abstract":"Bladder cancer (BC) is a prevalent urological tumor with high recurrence rates, requiring long-term monitoring. Although cystoscopy is the primary diagnostic method, its invasiveness and cost hinder routine screening and follow-up. This study aimed to develop a novel diagnostic tool utilizing newly developed on-chip heating dPCR platform, which features integrated and rapid temperature control capabilities, for non-invasive BC detection. The dPCR platform is improved by integrating a multi-color detection system, enabling precise quantification of mutant allelic fraction (MAF) of TERT promoter mutations with a limit of detection (LOD) of 0.29%. Diagnostic performance is enhanced by integrating the NRN1 methylation biomarker and employing machine learning to optimize biomarker weighting. Testing the model on urine samples from controls (n = 35) and BC patients (n = 41) yielded a sensitivity of 0.92, specificity of 0.94, and an AUC of 0.98, surpassing conventional cytology in sensitivity while maintaining comparable specificity. Furthermore, the model effectively differentiated between normal controls and different stages, achieving accuracies of 0.92, 0.71, and 0.79 for NC, stage I, and stage II+ respectively. These findings suggest the proposed dPCR assays could serve as a sensitive and non-invasive approach for BC detection in clinical practice.","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"7 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141502706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0