Cancer letters最新文献

{"title":"Tumor metastasis and recurrence: The role of perioperative NETosis.","authors":"Fu Zeng, Yuwen Shao, Jingyi Wu, Jingwen Luo, Ying Yue, Yang Shen, Yanghanzhao Wang, Yuxin Shi, Dan Wu, Juan P Cata, Shuofei Yang, Hao Zhang, Changhong Miao","doi":"10.1016/j.canlet.2024.217413","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217413","url":null,"abstract":"<p><p>Although surgical resection of tumor mass remains the mainstay of curative therapeutic management for solid tumors, accumulating studies suggest that these procedures promote tumor recurrence and metastasis. Regarded as the first immune cells to fight against infectious or inflammatory insults from surgery, neutrophils along with their ability of neutrophil extracellular traps (NETs) production has attracted much attention. A growing body of evidence suggests that NETs promote cancer metastasis by stimulating various stages, including local invasion, colonization, and growth. Therefore, we discussed the mechanism of NETosis induced by surgical stress and tumor cells, and the contribution of NETs on tumor metastasis: aid in the tumor cell migration and proliferation, evasion of immune surveillance, circulating tumor cell adhesion and establishment of a metastatic niche. Lastly, we summarized existing NET-targeting interventions, offering recent insights into potential targets for clinical intervention.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"611 ","pages":"217413"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892282","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":"TIM3 on natural killer cells regulates antibody-dependent cellular cytotoxicity in HER2-positive gastric cancer.","authors":"Chikanori Tsutsumi, Kenoki Ohuchida, Hirono Tsutsumi, Yuki Shimada, Yutaka Yamada, Kiwa Son, Sayuri Hayashida, Naoki Katayama, Yuki Mochida, Chika Iwamoto, Nobuhiro Torata, Kohei Horioka, Koji Shindo, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Keiichi Ota, Eiji Iwama, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Takashi Morisaki, Yoshinao Oda, Isamu Okamoto, Masafumi Nakamura","doi":"10.1016/j.canlet.2024.217412","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217412","url":null,"abstract":"<p><p>Therapies targeting HER2 are the standard treatment for HER2-positive gastric cancer (GC). Trastuzumab, a monoclonal antibody against HER2, exerts anti-tumor activity through cell growth regulation and antibody-dependent cellular cytotoxicity (ADCC). ADCC is induced by the binding of trastuzumab to Fcγ receptor III (CD16) in natural killer (NK) cells. However, the relationship between immune checkpoint (IC) molecules of NK cells and trastuzumab-induced ADCC is poorly understood. We performed single-cell RNA sequencing (scRNA-seq) and immunohistochemistry to identify IC molecules associated with CD16 expression in NK cells of GC patients. Additionally, we conducted in vitro assays with HER2-transfected GC cells and in vivo experiments using a mouse HER2-positive GC model to assess expression changes in IC molecules in NK cells and their ligands during trastuzumab treatment. In GC patients, the expression of TIM3, an IC molecule, was strongly correlated with that of CD16 in NK cells. In vitro assays showed that ADCC with trastuzumab increased TIM3 expression in NK cells. scRNA-seq analysis revealed that TIM3 expression of cytotoxic NK cells was elevated in HER2-positive GC patients treated with trastuzumab. HMGB1, a TIM3 ligand, was expressed at higher levels in HER2-transfected GC cells than in controls. Furthermore, HMGB1 expression was higher in HER2-positive GC patients treated with trastuzumab compared to untreated HER2-positive GC patients. In the mouse HER2-positive GC model, anti-TIM3 antibodies and trastuzumab demonstrated synergistic anti-tumor effects without toxicity. This study suggests the combined anti-TIM3 antibody and trastuzumab therapy may have potential as a new treatment strategy for HER2-positive GC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"611 ","pages":"217412"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892279","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":"WEE1 confers resistance to KRAS^G12C inhibitors in non-small cell lung cancer.","authors":"Gaku Yamamoto, Kosuke Tanaka, Ryo Kamata, Hitoshi Saito, Tomoko Yamamori-Morita, Takehiro Nakao, Jie Liu, Shunta Mori, Shigehiro Yagishita, Akinobu Hamada, Yuki Shinno, Tatsuya Yoshida, Hidehito Horinouchi, Yuichiro Ohe, Shun-Ichi Watanabe, Yasushi Yatabe, Hidenori Kitai, Satoshi Konno, Susumu S Kobayashi, Akihiro Ohashi","doi":"10.1016/j.canlet.2024.217414","DOIUrl":"10.1016/j.canlet.2024.217414","url":null,"abstract":"<p><p>KRAS^G12C inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS^G12C-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS^G12C inhibitors must be developed. Through unbiased high-throughput screening of 1395 kinase inhibitors, we identified adavosertib, a WEE1 inhibitor, as a promising combination partner of sotorasib. The combination of sotorasib and adavosertib exhibited synergistic antiproliferative activities both in vitro and in vivo, irrespective of TP53, STK11, and KEAP1 co-mutation profiles. WEE1 inhibition potentiated MCL-1-mediated apoptosis in sotorasib-treated cancer cells. Mechanistically, the combination downregulated MCL-1 protein levels by attenuating de novo translation and enhancing its degradation. WEE1 overexpression conferred resistance against sotorasib via MCL-1 upregulation. Moreover, cells that acquired sotorasib resistance profoundly upregulated both WEE1 and MCL-1 proteins, highlighting WEE1 as a crucial driver of sotorasib resistance. Importantly, WEE1 inhibition re-sensitized resistant cells to sotorasib treatment. The current findings demonstrate that combined inhibition of KRAS^G12C and WEE1 not only exhibits synergistic antitumor efficacy but also overcomes resistance to KRAS^G12C inhibitors, thus representing a novel therapeutic strategy for KRAS^G12C-mutant NSCLC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217414"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892326","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 mechanistic, functional, and clinical perspective on targeting CD70 in cancer.","authors":"Sandeep Kumar, Sowdhamini Mahendiran, Rakesh Sathish Nair, Harsh Vyas, Sunil Kumar Singh, Piush Srivastava, Saket Jha, Basabi Rana, Ajay Rana","doi":"10.1016/j.canlet.2024.217428","DOIUrl":"10.1016/j.canlet.2024.217428","url":null,"abstract":"<p><p>The oncoimmunology research has witnessed notable advancements in recent years. Reshaping the tumor microenvironment (TME) approach is an effective method to improve antitumor immune response. The T cell-mediated antitumor response is crucial for favorable therapeutic outcomes in several cancers. The United States Food and Drug Administration (FDA) has approved immune checkpoint inhibitors (ICIs) for targeting the immune checkpoint proteins (ICPs) expressed in various hematological and solid malignancies. The ICPs are T cell co-inhibitory molecules that block T cell activation and, thus, antitumor response. Currently, most of the FDA-approved ICIs are antagonistic antibodies of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). In contrast to ICPs, the T cell costimulatory molecules are required for T cell activation, expansion, and effector function. However, the abrupt expression of these costimulatory molecules in tumors presents a concern for T cell-mediated antitumor response. One of the T cell costimulatory molecules, the cluster of differentiation 70 (CD70), has emerged as a druggable target in various hematological and solid malignancies due to its role in T cell effector function and immune evasion. The present review describes the expression of CD70, factors affecting the CD70 expression, the physiological and clinical relevance of CD70, and the current approaches to target CD70 in hematological and solid malignancies.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217428"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892266","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":"m6A demethylation of NNMT in CAFs promotes gastric cancer progression by enhancing macrophage M2 polarization.","authors":"Tsz Kin Mak, Kuan Li, Zidan Zhao, Kexin Wang, Leli Zeng, Qilang He, Weiqun Lu, Wei Chen, Yulong He, Jia Li, Changhua Zhang","doi":"10.1016/j.canlet.2024.217422","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217422","url":null,"abstract":"<p><p>Cancer associated fibroblasts (CAFs) are the predominant stromal cells in the tumor microenvironment of gastric cancer (GC), interacting with both immune and tumor cells to drive cancer progression. However, the precise link between these interactions and their potential as therapeutic targets remains poorly understood. In this study, we identified for the first time that nicotinamide N-methyltransferase (NNMT) derived from CAFs promoted M2 macrophage polarization, which, in turn, facilitated the proliferation and migration of GC cells. Additionally, we discovered that NNMT expression in CAFs was regulated by the Fat mass and obesity related protein (FTO) via m6A demethylation. Both NNMT and FTO were highly expressed in tumor tissues and CAFs, with a positive correlation between FTO and NNMT levels in clinical samples. Mechanistically, FTO bound to NNMT mRNA, reducing m6A modification and enhancing NNMT expression. Knockdown of either NNMT or FTO in CAFs effectively inhibited M2 macrophage polarization and suppressed GC progression. These findings were validated in patient-derived organoid models and nude mouse models of GC. Collectively, our data revealed that FTO promoted M2 macrophage polarization by regulating the m6A demethylation of NNMT in CAFs, thereby driving GC progression. This identified a potential novel target for GC diagnosis and therapy.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217422"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892306","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":"Neutrophils in cancer drug resistance: Roles and therapeutic opportunities.","authors":"Hao Liu, Hongyu Zhao, Mingzhen Zhou, Xiaodi Zhao, Yuanyuan Lu","doi":"10.1016/j.canlet.2024.217417","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217417","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is closely associated with the therapeutic response and clinical outcome of cancer drug therapies, which mainly include immunotherapy, chemotherapy and targeted therapy. Neutrophils that infiltrate tumors, also known as tumor-associated neutrophils (TANs), constitute a primary part of the TME. However, the functional importance of TANs in cancer drug therapy has long been overlooked because of their relatively short life span. Recent studies have shown that TANs play crucial protumoral or antitumoral roles in cancer drug treatment, largely because of their diversity and plasticity. This review describes the development, heterogeneity and recruitment of neutrophils in the context of cancer and emphasizes the role and mechanisms of TANs in cancer drug resistance. Additionally, several potential neutrophil-targeted strategies are discussed.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"611 ","pages":"217417"},"PeriodicalIF":9.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892275","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":"FSTL1 sustains glioma stem cell stemness and promotes immunosuppressive macrophage polarization in glioblastoma.","authors":"Fengqi Zhou, Jincheng Tao, Huiqing Gou, Shuheng Liu, Dong Yu, Junxia Zhang, Jianxiong Ji, Ning Lin, Yingyi Wang","doi":"10.1016/j.canlet.2024.217400","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217400","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) play a crucial role in glioblastoma (GBM) progression by interacting with glioma stem cells (GSCs). These interactions lead to the polarization of TAMs toward an M2 phenotype, which, in turn, enhances the stem-like traits and malignant progression of GSCs. Our study shows that FSTL1, a protein released by GSCs, is significantly elevated in gliomas and linked to the progression of the disease. By suppressing FSTL1 in a mouse model, we observed reduced tumor growth and a decrease in M2 macrophages. In vitro studies show that FSTL1 from GSCs promotes M2 polarization and infiltration. Importantly, GSCs utilize autocrine FSTL1 to interact with TLR2, which inhibits the endocytosis-lysosomal degradation pathway mediated by EGFR, resulting in the activation of the PI3K-AKT signaling pathway that is critical for maintaining their self-renewal. These findings underscore the importance of FSTL1 in GSC maintenance and M2 macrophage polarization, suggesting that interventions targeting the FSTL1/TLR2 pathway could provide a novel therapeutic approach for GBM patients.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"611 ","pages":"217400"},"PeriodicalIF":9.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892336","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":"Enhancing cancer radiotherapy efficacy using NanOx, a novel oxygenating perfluorocarbon nanoemulsion that reverses tumour hypoxia.","authors":"Maitiú Ó Murchú, Xuehua Lin, Melissa Anne Tutty, Christina Cahill, Ian Miller, Lasse Jensen, Adriele Prina-Mello, Niamh Lynam-Lennon, Stephen G Maher, Helena Kelly, Jacintha O'Sullivan","doi":"10.1016/j.canlet.2024.217406","DOIUrl":"10.1016/j.canlet.2024.217406","url":null,"abstract":"<p><p>Radiotherapy is used to treat over 50 % of cancer patients. It is often used in combination with surgery, chemotherapy, and immunotherapy, for cancers of the breast, lung, oesophagus, and rectum. Ionising radiation predominantly exerts its anti-cancer effect through both direct DNA damage and indirectly via water radiolysis and the production of reactive oxygen species. This DNA damage is made permanent in the presence of molecular oxygen; however, it is reversible under hypoxia. Therefore, hypoxia confers significant radiotherapy resistance and given that it is a common feature of most solid tumours it offers a unique tumour vulnerability to exploit to improve radiotherapy efficacy. Many efforts to increase radiotherapy efficacy by oxygen delivery have failed due to limited efficacy and toxicity. To address this, we have developed a biocompatible, oxygenating perfluorocarbon nanoemulsion (nPFC) with imaging capacity via microCT with the view of delivering this intratumourally. We have demonstrated that this nPFC is biocompatible using an in vitro 3D liver hepatotoxicity model and in vivo using a developmental zebrafish embryo model. We have also shown that our nPFC can load and deliver a significant amount of molecular oxygen, reverse hypoxia, and enhance cellular radiosensitivity in an established in vitro isogenic model of acquired radioresistance in oesophageal adenocarcinoma (OAC) in accordance with the oxygen enhancement effect. Overall, this study demonstrates a potential method of enhancing cancer radiotherapy efficacy by locoregional oxygen delivery to hypoxic cells with acquired radioresistance.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217406"},"PeriodicalIF":9.1,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880665","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":"Targeting UBE2T suppresses breast cancer stemness through CBX6-mediated transcriptional repression of SOX2 and NANOG.","authors":"Keshen Wang, Qichen He, Xiangyan Jiang, Tao Wang, Zhigang Li, Huiguo Qing, Yuman Dong, Yong Ma, Bin Zhao, Junchang Zhang, Haonan Sun, Zongrui Xing, Yuxia Wu, Wenbo Liu, Junhong Guan, Ailin Song, Yan Wang, Peng Zhao, Long Qin, Wengui Shi, Zeyuan Yu, Huinian Zhou, Zuoyi Jiao","doi":"10.1016/j.canlet.2024.217409","DOIUrl":"10.1016/j.canlet.2024.217409","url":null,"abstract":"<p><p>Breast cancer stem cells (BCSCs) are the main cause of breast cancer recurrence and metastasis. While the ubiquitin-proteasome system contributes to the regulation of BCSC stemness, the underlying mechanisms remain unclear. Here, we identified ubiquitin-conjugating enzyme E2T (UBE2T) as a pivotal ubiquitin enzyme regulating BCSC stemness through systemic screening assays, including single-cell RNA sequencing (scRNA-seq) and stemness-index analysis. We found that patients with high UBE2T expression exhibited worse prognosis than those with low expression (10-year PFS: 55.95 % vs. 85.08 %), which are consistent across various subtypes of breast cancers. Genetic ablation of UBE2T suppresses BCSC stemness and tumor progression in organoids and spontaneous MMTV-PyMT mice, dependent on the transcriptional inactivation of pluripotency genes SOX2 and NANOG. Mechanically, UBE2T collaborates with the E3 ligase TRIM25 to perform K48-linked polyubiquitination and degradation of CBX6 at K214, which deficiency helps to promote the transcription of SOX2 and NANOG and enhances BCSC stemness. The pharmacological inhibitor of UBE2T significantly reduced the expression of NANOG and SOX2, suppressed tumor progression, and demonstrated synergistic effects when combined with chemotherapeutics, but not with other treatments. Collectively, our study revealed that the UBE2T-TRIM25-CBX6 axis can regulate BCSC stemness and offers a potentially therapeutic strategy to combat breast cancer in a clinical translation setting.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217409"},"PeriodicalIF":9.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880897","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":"Salivary adenoid cystic carcinoma-derived α2,6-sialylated extracellular vesicles increase vascular permeability by triggering ER-stress in endothelial cells and promote lung metastasis.","authors":"Qi Dong, Ming Dong, Xue Liu, Jiasheng Zhou, Saixuan Wu, Ziyao Liu, Weidong Niu, Tingjiao Liu","doi":"10.1016/j.canlet.2024.217407","DOIUrl":"10.1016/j.canlet.2024.217407","url":null,"abstract":"<p><p>Salivary adenoid cystic carcinoma (SACC) tends to metastasize to the lungs in the early stages of the disease. Factors secreted by the primary tumor can induce the formation of a supportive microenvironment in distant organs prior to metastasis, a process known as pre-metastatic niche (PMN) formation. Extracellular vesicles (EVs) participate in PMN formation. In this study, α2,6-sialylation of EVs derived from SACC cells with high metastatic potential increased vascular permeability, thereby facilitating tumor metastasis to the lungs. Mechanistic studies indicated that EV α2,6-sialylation triggers protein kinase R-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (eIF2α)-dependent activation of endoplasmic reticulum (ER) stress in the endothelium, leading to the disruption of vascular endothelial cadherin membrane expression. Sialidase or an ER stress inhibitor rescued vascular permeability induced by SACC EVs, which decreased the number of SACC cells extravasating into the lungs both in vitro and in vivo. This study identified a critical role of α2,6-sialylation of SACC EVs in lung metastasis. The findings indicate that EV α2,6-sialylation-induced ER stress in endothelial cells might be a therapeutic target for preventing SACC lung metastasis.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217407"},"PeriodicalIF":9.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876169","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}