Cancer Science最新文献

{"title":"Epithelial-Mesenchymal Transition and Genetically Driven Early Tumor Seedings in Extraneural Metastasis of Glioblastoma.","authors":"Seisaku Kanayama, Kentaro Watanabe, Minoru Tanaka, Junko Takita, Tomoki Todo","doi":"10.1111/cas.70126","DOIUrl":"https://doi.org/10.1111/cas.70126","url":null,"abstract":"<p><p>Genetic and cell biological analyses of this rare glioblastoma (GBM) case with rapidly progressive pleural metastasis revealed essential roles of epithelial-mesenchymal transition (EMT) and glioma stem-like cells (GSCs) in extraneural metastasis. Contrary to the common prediction, the metastatic lesion shared 73% of mutations and two fusion genes with the primary but not the recurrent tumor, indicating that extraneural metastasis occurs early in GBM progression. Functional assays using primary tumor-derived GSCs confirmed EMT-enhanced migratory behaviors. EMT and genetically driven early tumor seedings are crucial for extraneural GBM metastasis, emphasizing the need for further investigation into EMT pathways and GSC biology.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression.","authors":"Kosuke Hirose, Takaaki Masuda, Hajime Otsu, Taro Tobo, Kiyotaka Hosoda, Tadashi Abe, Yusuke Nakano, Masahiro Hashimoto, Takanari Tatsumi, Tomohiko Ikehara, Takashi Ofuchi, Shinsaku Itoyama, Yuki Ando, Yasuo Tsuda, Yusuke Yonemura, Keishi Sugimachi, Eiji Oki, Tomoharu Yoshizumi, Koshi Mimori","doi":"10.1111/cas.70119","DOIUrl":"https://doi.org/10.1111/cas.70119","url":null,"abstract":"<p><p>Polarity genes form intracellular protein complexes that establish epithelial cell polarity and homeostasis for various normal cellular functions. Partitioning Defective 6B (PARD6B), a polarity gene, functions as a scaffold node for the Par protein complex. However, its contribution to colon cancer is not well understood. In this study, we showed that PARD6B regulates tumor progression in colorectal cancer (CRC). PARD6B is located on chromosome 20, which is frequently amplified in CRC, and its expression in CRC correlates with DNA copy number amplification, including enhancer regions. Immunohistochemistry and single-cell analyses also showed that PARD6B expression was significantly higher in cancer cells. Furthermore, unlike other polarity gene groups comprising the Par complex, PARD6B mRNA expression was the only independent poor prognostic factor. In vitro and in vivo experiments revealed that PARD6B positively regulates cell proliferation and cell cycle progression. In silico analysis also showed that PARD6B expression positively regulated MYC expression, a pathway believed to be associated. Additional in silico and in vitro analyses supported the hypothesis that PARD6B regulates miR-34c, which directly targets and represses MYC expression. Pan-cancer analysis indicated that PARD6B is highly expressed in gastrointestinal tumors, including CRC, and that high PARD6B mRNA expression is a poor prognostic factor in other cancer types. In summary, highly expressed PARD6B can promote CRC growth by upregulating MYC expression while suppressing miR-34c expression, making PARD6B a potential prognostic biomarker and therapeutic target for CRC.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selinexor Reduces the Immunosuppression of Macrophages and Synergizes With CD19 CAR-T Cells Against B-Cell Lymphoma.","authors":"Wenjing Luo, Jia Xu, Chenggong Li, Lu Tang, Yingying Li, Xindi Wang, Zhuolin Wu, Yinqiang Zhang, Heng Mei, Yu Hu","doi":"10.1111/cas.70123","DOIUrl":"https://doi.org/10.1111/cas.70123","url":null,"abstract":"<p><p>CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved high response rates in patients with B-cell lymphoma. However, treatment failure and relapse can be attributable to CAR-T cell dysfunction and the immunosuppression of the tumor microenvironment. Combination therapy emerges as a solution strategy, and selinexor might be a potential candidate. In this study, we first established the ex vivo tumor microenvironment model by coculturing tumor cells and macrophages, followed by coculture with CAR-T cells, and identified that selinexor decreased CAR-T cell exhaustion and enhanced its cytotoxicity. Moreover, selinexor upregulated NGFR expression and boosted CAR-T cell proliferation. The ex vivo and in vivo results showed that selinexor prevented macrophages from polarizing to M2 populations. In the xenograft animal model, the sequential use of selinexor and CAR-T cells significantly reduced the tumor burden compared with selinexor or CAR-T cell monotherapies. In summary, our findings suggest that selinexor mitigates the immunosuppression of macrophages and improves CAR-T cell functionality, and the combination of selinexor and CAR-T cells may be a promising therapeutic strategy for B-cell lymphoma.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered EVs-Mediated miR-222 Targeting PTEN/FN1 Axis Reverses Anthracycline Resistance in HER2-Negative Breast Cancer.","authors":"Sujin Yang, Mei Yang, Quanfeng Shao, Dandan Wang, Shanliang Zhong, Suyu Yang, Haiyan Gao, Xihu Qin, Weixian Chen","doi":"10.1111/cas.70118","DOIUrl":"https://doi.org/10.1111/cas.70118","url":null,"abstract":"<p><p>Anthracycline resistance represents a critical therapeutic challenge in breast cancer treatment, wherein alterations in the tumor immune microenvironment and enhanced cellular resistance mechanisms facilitate chemoresistance progression. Transcriptome analysis of 142 HER2-negative breast cancer patients undergoing anthracycline-based chemotherapy revealed four distinct tumor-infiltrating cell subtypes, with subtype D exhibiting elevated M1 macrophage infiltration and superior prognostic outcomes. Differential expression analysis identified miR-222 as the predominantly upregulated microRNA in adriamycin-resistant cells, while Tandem Mass Tag mass spectrometry-based quantitative analysis elucidated PTEN as its direct target and FN1 as a crucial downstream mediator. Engineered extracellular vesicles (EVs) carrying a miR-222 inhibitor were developed to reverse adriamycin resistance via PTEN/FN1 signaling modulation. Molecular docking analysis found specific PTEN-FN1 protein interactions characterized by stable hydrogen bonds at ARG142-ASP23 and ARG15-GLU95. In xenograft models, EVs-mediated delivery of the miR-222 inhibitor significantly attenuated MCF-7/ADR tumor progression through miR-222 suppression and PTEN restoration, with concordant molecular alterations observed in serum-derived EVs. Our findings establish a novel mechanism of EVs-mediated drug resistance through the microRNA-222/PTEN/FN1 axis and present Engineered EVs as a promising therapeutic strategy for anthracycline resistance in breast cancer, while highlighting circulating EVs profiles as potential treatment monitoring biomarkers.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of KLHL Gene Family Member KLHL5 in Colorectal Cancer Progression and Prognosis.","authors":"Konomu Uno, Hirotada Nishie, Hiromi Hiyoshi, Kyosuke Habu, Jun Nakayama, Sota Tate, Tomohisa Sakaue, Eiji Kubota, Mamoru Tanaka, Takaya Shimura, Hiromi Kataoka, Takashi Joh, Shigeki Higashiyama","doi":"10.1111/cas.70107","DOIUrl":"https://doi.org/10.1111/cas.70107","url":null,"abstract":"<p><p>The KLHL gene family member KLHL5, which is a constituent factor of the RING E3 ubiquitin ligase complex, is expressed in various types of cancers and plays a role in cancer pathophysiology. In this study, we identified KLHL5 as a potential biomarker for predicting the prognosis of colorectal cancer (CRC) from 42 KLHL family genes using transcriptome profiles generated by RNA-seq analysis of The Cancer Genome Atlas colorectal adenocarcinoma (TCGA-COAD). We further investigated the implication of KLHL5 in CRC using pathological examination and bioinformatics analyses. Clinicopathological analyses revealed that KLHL5 was more highly expressed in CRC than in adjacent normal mucosa, and its expression level increased concomitantly with the CRC stage (p < 0.05). KLHL5 expression was associated with poor prognostic factors such as depth of invasion (p < 0.001), lymphovascular invasion (p = 0.029), and lymph node metastasis (p = 0.025). Notably, KLHL5 exhibited heterogeneous expression within the tumor, with pronounced expression observed at the invasive front of the tumor (p < 0.0001). Through bioinformatics analyses, we determined that elevated KLHL5 expression in CRC is significantly associated with poor prognosis. Furthermore, analysis from the Gene Expression Omnibus database indicated that KLHL5 expression was more pronounced in the common molecular subtype (CMS) 4 CRC, which is characterized as highly advanced, and the overall and recurrence-free survival rates were poor compared to other CMS groups. Our findings indicate that KLHL5 plays a pivotal role in the progression and development of CRC, and can be used as a potential biomarker and therapeutic target for CRC treatment.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric Signet Ring Cell Carcinoma in a Helicobacter pylori-Positive 10-Year-Old Boy: A Case Report and Literature Review.","authors":"Xiaoxuan Li, Xinchi Luan, Wenjuan Yu, Shibo Wang, Xiangxue Li, Lihua Zhang, Siyi Zhang, Jialin Song, Jing Guo, Shasha Wang, Wensheng Qiu, Jing Lv","doi":"10.1111/cas.70112","DOIUrl":"https://doi.org/10.1111/cas.70112","url":null,"abstract":"<p><p>Gastric cancer is rare in pediatric populations, with gastric signet ring cell carcinoma (GSRCC) being an exceptionally infrequent subtype. We report a case of GSRCC in a 10-year-old Chinese boy with no family history of cancer. The diagnosis was established via gastroscopy, endoscopic ultrasound, and imaging examinations. Early detection allowed a successful distal gastrectomy with D2 lymph node dissection. Postoperative whole-exome sequencing (WES) revealed no clinically significant mutations but identified some somatic alterations. Notably, gastric biopsy pathology demonstrated strong positivity for Helicobacter pylori (H. pylori) infection. Additionally, we comprehensively reviewed the existing pediatric GSRCC cases, suggesting the potential role of H. pylori infection in the pathogenesis of pediatric gastric cancer.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PC4 Potentially Predicts Chemoradiation-Induced Antitumor Immunity in Esophageal Squamous Cell Carcinoma.","authors":"Jieyong Tian, Xiaoying Wei, Huiquan Liu, Qingsong Pang, Dong Qian, Haiming Dai","doi":"10.1111/cas.70117","DOIUrl":"https://doi.org/10.1111/cas.70117","url":null,"abstract":"<p><p>Chemoradiotherapy (CRT) induces an antitumor immune response in esophageal squamous cell carcinoma (ESCC), and thereby has enormous potential by itself and in combination with immune checkpoint inhibitors (ICI). Our previous studies indicated that human positive cofactor 4 (PC4) was an independent predictor of poor survival in patients with ESCC or lung cancer who were treated with definitive chemoradiation, with a mechanism involving the enhancement of nonhomologous end joining (NHEJ)-mediated DNA repair. Due to the important role of double-strand DNA (dsDNA) in the antitumor immune response, the present study aims to investigate PC4 as a predictor of pathological response and antitumor immune response in ESCC patients who underwent neoadjuvant CRT. In ESCC, low PC4 expression levels have significant power to predict pCR. In particular, pCR is 61.2% in patients with low PC4 expression, but only 23.4% in patients with high PC4. Both disease-free survival (DFS) and overall survival (OS) are significantly longer for patients with low PC4 than for those with high PC4. In agreement with our previous finding that PC4 participates in NHEJ-mediated DNA repair, our further analysis indicates that the expression of PC4 is not only significantly negatively correlated with cyto-free dsDNA in postoperative specimens, but also with tumor-infiltrating CD8⁺T lymphocytes (CD8⁺TILs) and GZMB⁺CD8⁺TILs, suggesting a possible mechanism that high PC4 negatively regulates the antitumor response and therefore results in poor prognosis. Together, our findings demonstrate that low expression of PC4 is a potential biomarker for predicting the antitumor immune response to chemoradiation in patients with operable locally advanced ESCC.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dauricine Overcomes Osimertinib Resistance in Lung Cancer by Inducing Ferroptosis via Stabilizing SAT1.","authors":"Biying Men, Zhijie Chen, Haotian Ge, Zhuoying Yang, Liang Yun, Jianjun Jiang, Meijuan Dian, Yujing He, Zehao Zhou, Ruihao Zhang, Tianbao Yan, Zichao Li, Yingxin Zhang, Yongjie He, Junming He, Xuguang Rao, Shuan Rao","doi":"10.1111/cas.70113","DOIUrl":"https://doi.org/10.1111/cas.70113","url":null,"abstract":"<p><p>Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) widely used to treat advanced nonsmall cell lung cancer (NSCLC) with EGFR mutations. However, resistance to osimertinib frequently develops, limiting its long-term effectiveness. In this study, we used osimertinib-resistant lung cancer cell lines and lung cancer patient-derived organoids to demonstrate the potential of dauricine, a bioactive compound derived from menispermum dauricum, to overcome osimertinib resistance in lung cancer cells. Mechanistic studies reveal that dauricine, when combined with osimertinib, efficiently induces ferroptosis in resistant lung cancer cells. Notably, RNA interference and pharmacological inhibition assays identify SAT1, a key enzyme involved in polyamine metabolism and oxidative stress regulation, as a critical mediator of the synergistic effects observed with the dauricine-osimertinib combination therapy. Furthermore, we show that dauricine can directly interact with and stabilize SAT1 to enhance its activity. In vivo, when administered with osimertinib, dauricine significantly suppresses tumor growth in osimertinib-resistant lung cancer models. These findings provide novel insights into the role of SAT1 in overcoming osimertinib resistance and suggest that combining dauricine with osimertinib could be a promising therapeutic strategy to improve the efficacy of EGFR-TKI therapy in resistant NSCLC.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Histone Methyltransferase SETDB1 in Normal and Malignant Hematopoiesis.","authors":"Yu-Hsuan Chang, Susumu Goyama","doi":"10.1111/cas.70116","DOIUrl":"https://doi.org/10.1111/cas.70116","url":null,"abstract":"<p><p>SET domain bifurcated histone methyltransferase 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase, functioning in transcriptional silencing of the transposable elements (TEs), endogenous retroviruses (ERVs), interferon-stimulated genes (ISGs), and immune cell-related molecules. SETDB1 collaborates with cofactors such as ATF7IP and TRIM28 and functions in concert with DNA methylation to maintain gene repression in both stem cells and differentiated somatic cells. Given its gene targets, recent studies have shown that SETDB1 is a critical immune checkpoint gene in both solid and hematological tumors. In this review, we first discuss the role of SETDB1 in gene regulation through its histone methyltransferase activity, including an overview of its structural features and key cofactors. We then highlight the lineage-specific roles of SETDB1 in both normal hematopoietic processes and hematological malignancies, emphasizing its function as an immune checkpoint molecule that suppresses natural killer (NK) cell-mediated antileukemia responses.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Profiling Reveals the Distinctions Among MTX-Associated DLBCL, EBV-Positive Mucocutaneous Ulcer, and EBV + DLBCL.","authors":"Takumi Takahashi, Keisuke Sawada, Takahisa Yamashita, Wataru Yamamoto, Yosuke Iijima, Akiko Adachi, Makoto Kashimura, Takayuki Tabayashi, Masahiro Kizaki, Takahiro Kaneko, Jun-Ichi Tamaru, Morihiro Higashi, Shuji Momose","doi":"10.1111/cas.70111","DOIUrl":"https://doi.org/10.1111/cas.70111","url":null,"abstract":"<p><p>The WHO recently changed the outline of immunodeficiency/dysregulation (IDD)-associated lymphoproliferative disorders (LPDs)/lymphomas from underlying IDD settings to an overarching framework and accommodates commonalities in histology, the involvement of various oncogenic viruses, and specific clinical/therapeutic consequences. A mutational analysis has been performed on post-transplantation and HIV-positive lymphomas, but not on other iatrogenic immunodeficiency (OII)-associated LPDs mainly caused by methotrexate (MTX) to treat rheumatoid arthritis. We herein conducted next-generation sequencing (NGS) to examine the genetic spectrum along with a fluorescence in situ hybridization analysis of 9p24.1 and PD-L1 expression in 37 MTX-associated diffuse large B-cell lymphoma (DLBCL) cases, 17 Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) cases, and 26 EBV-positive DLBCL (EBV + DLBCL) cases. Targeted NGS identified 177 mutations. The mutation frequency was significantly higher in EBV^- MTX-DLBCL than in EBV-positive LPDs/lymphomas (EBVMCU, EBV⁺ MTX-DLBCL, and EBV + DLBCL). Regrowth or resistance to spontaneous regression after MTX withdrawal was more likely in EBV^- MTX-DLBCL than in EBV⁺ MTX-DLBCL. Therefore, accumulated gene mutations, sustained by the restored immune status in EBV^- MTX-DLBCL, may affect clinical outcomes after MTX discontinuation. Several unique genetic findings were obtained for each category. Fewer TET2/DNMT3A and CD58 mutations in OII-LPD/lymphomas (EBVMCU and MTX-DLBCL) than in EBV + DLBCL indicate that clonal hematopoiesis and an immune evasion-related background contributed less to lymphomagenesis in OII-LPDs. MYD88^L265P/CD79B^Y196 mutations were only detected in EBV^- MTX-DLBCL. SOCS1 mutations were significantly more frequent in EBV-positive LPD/lymphoma categories, irrespective of the immune status, than in EBV^- MTX-DLBCL. These results reveal distinct genetic features among MTX-DLBCL (EBV+/-), EBVMCU, and EBV + DLBCL.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}