Drug Resistance Updates最新文献

{"title":"HSA-templated synergistic platform boosts radiotherapy via enhanced radiosensitization and ferroptosis induction","authors":"Xiaofei Fan ,&nbsp;Jiahao Liu ,&nbsp;Shudong Xie ,&nbsp;Hongpei Tan ,&nbsp;Ze Mi ,&nbsp;Pengpeng Zhang ,&nbsp;Xiaoqian Ma ,&nbsp;Qi Liang ,&nbsp;Min Yang ,&nbsp;Yingzi Ming ,&nbsp;Pengfei Rong","doi":"10.1016/j.drup.2025.101293","DOIUrl":"10.1016/j.drup.2025.101293","url":null,"abstract":"<div><div>Radiotherapy efficacy in cancer treatment is frequently compromised by tumor radioresistance, limited immune activation, and off-target toxicity. To address these challenges, we developed a multifunctional nanosystem (FPPF@HC), combining FePt-PEG-FA nanoparticles encapsulated in an HSA-CaP hybrid shell. This platform prolongs systemic circulation, effectively targets tumors via the enhanced permeability and retention effect, and facilitates active folate receptor-mediated uptake. In the acidic tumor microenvironment, the nanoparticles release FePt cores, triggering ferroptosis through Fe²⁺-mediated Fenton reactions, oxidative stress, lipid peroxidation, and subsequent tumor cell death. Concurrently, ferroptosis-induced immunogenic cell death enhances dendritic cell maturation and CD8⁺ effector T cell infiltration, remodeling the tumor immune microenvironment. In vitro and in vivo studies demonstrated significantly improved tumor suppression, radiosensitivity, and immune activation compared with radiotherapy alone. Comprehensive biosafety evaluations indicated minimal systemic toxicity. This nanosystem offers a promising strategy for overcoming radioresistance and improving clinical outcomes in cancer therapy.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101293"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug resistance in breast cancer: Mechanisms and strategies for management","authors":"Guo-Yu Wu ,&nbsp;Ming-Zhu Xiao ,&nbsp;Wei-Chao Hao ,&nbsp;Zhao-Shou Yang ,&nbsp;Xin-Ran Liu ,&nbsp;Dian-Shuang Xu ,&nbsp;Zhong-Xing Peng ,&nbsp;Lu-Yong Zhang","doi":"10.1016/j.drup.2025.101288","DOIUrl":"10.1016/j.drup.2025.101288","url":null,"abstract":"<div><div>Therapeutic resistance remains a significant challenge in breast cancer treatment, often driven by factors such as genetic mutations, dysregulation of receptors and signaling pathways, alterations in drug metabolism and transport, cellular heterogeneity, and modifications in the tumor microenvironment. As a highly heterogeneous and complex disease, breast cancer exhibits distinct molecular and histopathological characteristics, necessitating tailored therapeutic approaches. This article reviews recent advancements in understanding therapy resistance across four major subtypes — Luminal A, Luminal B, HER2-enriched, and triple-negative breast cancer (TNBC) — and explores potential strategies to overcome resistance, providing insights into developing novel therapeutic interventions. Notably, TNBC patients have limited treatment options, with chemotherapy remaining the standard approach and immunotherapy emerging as an adjunct strategy. We concisely overview key mechanisms contributing to therapy resistance and discuss innovative therapeutic strategies, including combination regimens, molecularly targeted therapies, photodynamic therapy, and ferroptosis-inducing treatments. Additionally, we highlight recent advancements in multi-omics data integration and artificial intelligence-driven approaches in breast cancer research. Future efforts should focus on refining predictive models, optimizing combination therapies, and leveraging artificial intelligence to enhance treatment efficacy, ultimately overcoming resistance and improving long-term outcomes for breast cancer patients.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101288"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNF217-KEAP1-NRF2 feedback loop confers therapeutic resistance by inhibiting ferroptosis in esophageal squamous cell carcinoma","authors":"Sifen Wang ,&nbsp;Chao Zhang ,&nbsp;Sha Zhou ,&nbsp;Shiliang Liu ,&nbsp;Qiaoqiao Li ,&nbsp;Xingyuan Cheng ,&nbsp;Ruixi Wang ,&nbsp;Baoqing Chen ,&nbsp;Yue Li ,&nbsp;Mian Xi","doi":"10.1016/j.drup.2025.101296","DOIUrl":"10.1016/j.drup.2025.101296","url":null,"abstract":"<div><div>Resistance to chemoradiotherapy is a crucial factor limiting the efficacy of therapy and prognosis of esophageal cancer. It is necessary to elucidate the key genes and regulatory mechanisms responsible for therapeutic resistance in esophageal squamous cell carcinoma (ESCC). In this study, we found a relationship between ferroptosis and therapeutic sensitivity in ESCC and identified the ring finger protein 217 (RNF217) as a new regulator of ferroptosis associated with resistance to chemoradiotherapy in ESCC. Mechanistically, RNF217 interacts with kelch like ECH associated protein 1 (KEAP1) and promotes its ubiquitination and degradation, resulting in nuclear factor erythroid 2-related factor 2 (NRF2) evading KEAP1-mediated degradation and, consequently, enhanced NRF2 signaling and led to ferroptosis resistance. Furthermore, NRF2 facilitated the transcription of RNF217 by binding to antioxidant response elements in the RNF217 promoter upon irradiation. Overall, our findings indicate that the RNF217-KEAP1-NRF2 feedback loop is a previously unrecognized mechanism regulating resistance to chemoradiotherapy in ESCC and could be a target to overcome therapeutic resistance in ESCC.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101296"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteasomes suppress anticancer drug-induced cytotoxicity by inhibiting mitochondrial protein import and promoting ROS-BNIP3-mediated mitophagy","authors":"Ling Li ,&nbsp;Yangyang Feng ,&nbsp;Jingbo Zhou ,&nbsp;Fangyuan Shao ,&nbsp;Yuzhong Peng ,&nbsp;Sitian Zang ,&nbsp;Josh Haipeng Lei ,&nbsp;Heng Sun ,&nbsp;Dongyang Tang ,&nbsp;Shiqi Lin ,&nbsp;Jinghong Chen ,&nbsp;Hanghang Li ,&nbsp;Xiangpeng Chu ,&nbsp;Yunfeng Qiao ,&nbsp;Xinyu Guo ,&nbsp;Kakun Wu ,&nbsp;Xiaoling Xu ,&nbsp;Chu-Xia Deng","doi":"10.1016/j.drup.2025.101294","DOIUrl":"10.1016/j.drup.2025.101294","url":null,"abstract":"<div><div>Multidrug resistance (MDR) is associated with increased proteasome activity, which facilitates the clearance of damaged proteins and reduced mitochondrial activity, which contributes to quiescence. However, the mechanistic link between protein damage, mitochondrial dysfunction, and proteasome activity remains elusive. Here, we demonstrate that chemical drugs bind to newly synthesized mitochondrial proteins, which are largely unfolded and are coimported into the mitochondrion before appearing in the lysosome and/or nucleus. This triggers a mitochondrion-lysosome–mediated chain reaction, including the integrity stress response (ISR) and the mitochondrial unfolded protein response (UPR^mt), followed by increased lysosome biogenesis and PINK1–Parkin independent but ROS–BNIP3–mediated mitophagy. We further observed that proteasomes are the main controller of the mitochondrion-lysosome reaction by monitoring proteostasis, suppressing mitochondrial protein import and promoting mitophagy under both normal and drug-treated conditions. The combination of chemical drugs and the proteasome inhibitor bortezomib (BTZ) triggered excessive mitochondrial import of damaged proteins, overwhelming mitochondrial capacity, causing mitochondrial membrane damage, profound mitochondrial ROS production, lysosome membrane permeabilization, impaired mitophagy, and proteostasis stress-induced cell death.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101294"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering nanoplatforms of bacterial outer membrane vesicles to overcome cancer therapy resistance","authors":"Qing-Qing Chai ,&nbsp;Dan Li ,&nbsp;Min Zhang ,&nbsp;Yong-Wei Gu ,&nbsp;Ai-Xue Li ,&nbsp;Xin Wu ,&nbsp;Xiao-Yan Liu ,&nbsp;Ji-Yong Liu","doi":"10.1016/j.drup.2025.101277","DOIUrl":"10.1016/j.drup.2025.101277","url":null,"abstract":"<div><div>Resistance to cancer therapy is driven by physical barriers, tumor heterogeneity, selective therapeutic pressure, immunosuppressive tumor microenvironment (TME) and others. Bacterial outer membrane vesicles (OMVs) represent a promising nanotherapeutic platform to combat cancer therapy resistance. This review discusses the dual roles of OMVs in tumorigenesis and cancer therapy, highlighting their potential applications to enhance treatment efficacy. OMVs from pathogenic bacteria, such as <em>Fusobacterium nucleatum</em> and <em>Helicobacter pylori</em>, exacerbate chemoresistance by reshaping TME through hypoxia-induced metabolic reprogramming and immune evasion, while OMVs from some bacteria, such as probiotics, counteract immunosuppression by promoting cytotoxic T-cell infiltration and macrophage polarization. As bio-derived and conveniently engineered drug delivery platforms, OMVs maximize the synergetic anticancer effect by pathogen associated molecular patterns and the payloads. These functional payloads include siRNAs, cytotoxicity and molecular agents, and immune checkpoint inhibitors. Bacterial OMVs demonstrate unique advantages through their capacity to penetrate physical barriers, achieve tumor-specific targeting, activate immune responses, to overcome cancer therapy resistance. A successful example is the OMV-based nanoplatform with engineered OMVs co-delivering CD47-siRNA and doxorubicin to overcome drug resistance by inducing immunogenic cell death and dendritic cell activation of glioblastoma. Furthermore, OMV-based cancer vaccines presented with tumor antigens or hybridized with tumor-derived membranes enhance dendritic cell maturation and antigen-specific T-cell responses, reversing treatment resistance. By addressing challenges in mass production and safety concerns, OMVs-based platforms can be developed as powerful tools for more effective and personalized cancer treatments.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101277"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining homologous recombination deficiency status in pancreatic ductal adenocarcinoma: Clinical implications for evaluating response to platinum chemotherapy","authors":"Yanxia Wang ,&nbsp;Fancheng Kong ,&nbsp;Xiaohua Situ ,&nbsp;Tiantian Yang ,&nbsp;Tianqi Sun ,&nbsp;Zhongpeng Xie ,&nbsp;Pingling Wang ,&nbsp;Yu Chen ,&nbsp;Neng Jiang ,&nbsp;Yu Dong ,&nbsp;Zhaofan Luo ,&nbsp;Zunfu Ke","doi":"10.1016/j.drup.2025.101291","DOIUrl":"10.1016/j.drup.2025.101291","url":null,"abstract":"<div><h3>Aims</h3><div>Pancreatic ductal adenocarcinoma (PDAC) remains a daunting malignancy with limited therapeutic options; effective biomarkers are needed to improve its treatment decision-making. The aim of this study is to evaluate the role of homologous recombination deficiency (HRD) in assessing the response to platinum chemotherapy in PDAC.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on 264 patients diagnosed with PDAC. Tumor tissue samples were subjected to next-generation sequencing (NGS) to assess DNA damage repair (DDR) gene mutation landscape and HRD score. The integrated HRD score was calculated as the unweighted sum of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transition (LST) scores. The associations between HRD status and clinical outcomes in patients receiving platinum treatment were systematically analyzed.</div></div><div><h3>Results</h3><div>Patients with <em>BRCA1/2</em> biallelic loss-of-function (BILOF) status and/or an HRD score ≥ 42 were predefined as HRD-positive. According to this HRD status definition, 4.9 % (n = 13) of the 264 patients were identified as HRD-positive, identifying a broader population than using <em>BRCA1/2</em> BILOF alone (1.9 %, n = 5). Patients with <em>BRCA1/2</em> mutations (<em>BRCA1/2 </em>^m), presented a lower frequency of alteration in genes related to non-homologous end joining (NHEJ) and mismatch repair (MMR) genes than those with <em>BRCA1/2</em> wild-type (<em>BRCA1/2 </em>^wt), with mutations observed in 46.15 % (6/13) of <em>BRCA1/2 </em>^m versus 72.91 % (183/251) of <em>BRCA1/2 </em>^wt patients. The median HRD score (23) in patients with DNA damage repair (DDR) gene BILOF mutations was notably higher than that in those with non-BILOF mutations in DDR genes (9). HRD-positive patients demonstrated markedly longer progression-free survival (PFS) (median PFS 44.1 months) than HRD-negative patients (median PFS 12.2 months) when the patients received first-line platinum-based adjuvant treatment (<em>P</em> = 0.035). Specifically, patients with <em>BRCA1/2</em> BILOF exhibited a substantial clinical benefit from platinum therapy, with none of these patients experiencing disease progression or death during follow-up.</div></div><div><h3>Conclusions</h3><div><em>BRCA1/2</em> BILOF plays a crucial role in identifying PDAC patients for first-line platinum-based adjuvant treatment, and HRD positive status, defined by <em>BRCA1/2</em> BILOF and/or an HRD score ≥ 42, broadens the pool of eligible patients, and helps avoid ineffective treatment due to intrinsic drug resistance.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101291"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets","authors":"Mingyang Jiang ,&nbsp;Jinlong Wang ,&nbsp;Yize Li ,&nbsp;Ke Zhang ,&nbsp;Tao Wang ,&nbsp;Zhandong Bo ,&nbsp;Shenyi Lu ,&nbsp;Raquel Alarcón Rodríguez ,&nbsp;Ruqiong Wei ,&nbsp;Mingtao Zhu ,&nbsp;Christophe Nicot ,&nbsp;Gautam Sethi","doi":"10.1016/j.drup.2025.101276","DOIUrl":"10.1016/j.drup.2025.101276","url":null,"abstract":"<div><div>Cancer continues to be a primary cause of death, resulting in substantial mortality and illness globally. It remains a significant global health issue, greatly affecting morbidity and mortality across the world. Therapeutic resistance poses a major challenge to cancer treatments, acting as a significant barrier to the effectiveness of both standard and targeted therapies. This resistance develops through various mechanisms that allow tumor cells to adapt to and escape the damaging effects of chemotherapy, radiation, and targeted therapies. Ultimately, this leads to disease recurrence and progression. This review examines the dual roles of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) in promoting chemoresistance and metastasis. EMT is a dynamic and reversible biological process in which epithelial cells acquire mesenchymal characteristics, increasing their invasiveness and resistance to programmed cell death. CSCs are a subset of cancer cells with the ability to self-renew and play a crucial role in tumor relapse and resistance to treatment. EMT and CSCs are closely interconnected, collaboratively enhancing cancer cell plasticity, metastatic ability, and treatment resistance. The initiation of EMT in cancer cells can generate a CSC-like population, which promotes tumor recurrence and spread. This interaction highlights the importance of targeting both EMT and CSC pathways to develop more effective treatment strategies that address treatment resistance and prevent metastasis. Promising approaches include using natural substances, small molecules, and nanotechnology to block critical signaling pathways and interfere with resistance mechanisms. A more thorough understanding of the molecular factors underlying EMT and CSC plasticity is crucial for crafting personalized treatments that target tumor heterogeneity and improve clinical outcomes.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101276"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “A highly potent small-molecule antagonist of exportin-1 selectively eliminates CD44+ CD24- enriched breast cancer stem-like cells” [Drug Resist. Updates 66 (2023) 100903]","authors":"Caigang Liu ,&nbsp;Yixiao Zhang ,&nbsp;Jiujiao Gao ,&nbsp;Qi Zhang ,&nbsp;Lisha Sun ,&nbsp;Qingtian Ma ,&nbsp;Xinbo Qiao ,&nbsp;Xinnan Li ,&nbsp;Jinchi Liu ,&nbsp;Jiawen Bu ,&nbsp;Zhan Zhang ,&nbsp;Ling Han ,&nbsp;Dongyu Zhao ,&nbsp;Yongliang Yang","doi":"10.1016/j.drup.2025.101297","DOIUrl":"10.1016/j.drup.2025.101297","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"Article 101297"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of synthetic lethality in overcoming cancer therapy resistance: Emerging paradigm and recent advances.","authors":"Qingyi Xiong, Jinmei Jin, Jiayi Lin, Bohan Zhang, Yixin Jiang, Zhe Sun, Lijun Zhang, Ye Wu, Guozhi Zhao, Jiang-Jiang Qin, Xin Luan","doi":"10.1016/j.drup.2025.101290","DOIUrl":"10.1016/j.drup.2025.101290","url":null,"abstract":"<p><p>Cancer therapy resistance remains a major barrier to successful treatment, often leading to reduced clinical efficacy or cancer relapse. Synthetic lethality (SL) has emerged as a promising strategy to exploit genetic vulnerabilities in cancer cells, allowing for more selective and less toxic therapies. By leveraging the genetic or non-genetic adaptations that cancer cells develop under therapeutic pressure, SL-based therapies provide a more precise and less toxic treatment approach. Additionally, SL-driven drug combinations not only delay development of drug resistance but also enhance therapeutic efficacy, representing a transformative shift in cancer management. A comprehensive understanding of SL mechanisms in the context of drug resistance is essential for advancing effective treatment strategies. This review highlights recent advances in SL research, emphasizing the gene screening techniques in overcoming cancer therapy resistance.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"83 ","pages":"101290"},"PeriodicalIF":21.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A covalent gambit: An irreversible inhibitor to checkmate drug resistance in tuberculosis","authors":"Chunxia Jiang, Dan Wang, Liujun Xu","doi":"10.1016/j.drup.2025.101314","DOIUrl":"https://doi.org/10.1016/j.drup.2025.101314","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"20 1","pages":"101314"},"PeriodicalIF":24.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}