Molecular Cancer最新文献

{"title":"PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies","authors":"Menglei Jin, Jun Fang, Junwen Peng, Xintian Wang, Ping Xing, Kunpeng Jia, Jianming Hu, Danting Wang, Yuxin Ding, Xinyu Wang, Wenlu Li, Zhigang Chen","doi":"10.1186/s12943-024-02176-8","DOIUrl":"https://doi.org/10.1186/s12943-024-02176-8","url":null,"abstract":"Immunotherapy targeting programmed cell death-1 (PD-1) and PD-L1 immune checkpoints has reshaped treatment paradigms across several cancers, including breast cancer. Combining PD-1/PD-L1 immune checkpoint blockade (ICB) with chemotherapy has shown promising efficacy in both early and metastatic triple-negative breast cancer, although only a subset of patients experiences durable responses. Identifying responders and optimizing immune drug selection are therefore critical. The effectiveness of PD-1/PD-L1 immunotherapy depends on both tumor-intrinsic factors and the extrinsic cell-cell interactions within the tumor microenvironment (TME). This review systematically summarizes the key findings from clinical trials of ICBs in breast cancer and examines the mechanisms underlying PD-L1 expression regulation. We also highlight recent advances in identifying potential biomarkers for PD-1/PD-L1 therapy and emerging evidence of TME alterations following treatment. Among these, the quantity, immunophenotype, and spatial distribution of tumor-infiltrating lymphocytes stand out as promising biomarkers. Additionally, we explore strategies to enhance the effectiveness of ICBs in breast cancer, aiming to support the development of personalized treatment approaches tailored to the unique characteristics of each patient’s tumor.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"37 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142753575","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":"Cancer liquid biopsies by Oxford Nanopore Technologies sequencing of cell-free DNA: from basic research to clinical applications","authors":"Hua-Qi Si, Peng Wang, Fei Long, Wei Zhong, Yuan-Dong Meng, Yuan Rong, Xiang-Yu Meng, Fu-Bing Wang","doi":"10.1186/s12943-024-02178-6","DOIUrl":"https://doi.org/10.1186/s12943-024-02178-6","url":null,"abstract":"Liquid biopsies, in particular, analysis of cell-free DNA, are expected to revolutionize the current landscape of cancer diagnostics and treatment. However, the existing methods for cfDNA-based liquid biopsies for cancer have certain limitations, such as fragment interruption and GC bias, which are likely to be resolved by the emerging Oxford Nanopore Technologies (ONT), characterized by long read-length, fast read-times, high throughput, and polymerase chain reaction-free. In this review, we summarized the current literatures regarding the feasibility and applications of cfDNA-based liquid biopsies using ONT for cancer management, a possible game-changer that we believe is promising in detecting multimodal biomarkers and can be applied in a wide range of oncology utilities including early screening, diagnosis, and treatment monitoring. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"69 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142753576","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":"Co-occurring mutations identify prognostic subgroups of microsatellite stable colorectal cancer","authors":"Luís Nunes, Jakob Mørkved Stenersen, Kushtrim Kryeziu, Tobias Sjöblom, Bengt Glimelius, Ragnhild A. Lothe, Anita Sveen","doi":"10.1186/s12943-024-02173-x","DOIUrl":"https://doi.org/10.1186/s12943-024-02173-x","url":null,"abstract":"Co-occurring mutations in pairs of genes can pinpoint clinically relevant subgroups of cancer. Most colorectal cancers (CRCs) are microsatellite stable (MSS) and have few frequent mutations. Large patient cohorts and broad genomic coverage are needed for comprehensive co-mutation profiling. Co-mutations were identified in a population-based Swedish cohort analyzed by whole-genome sequencing (n=819 stage I-IV MSS CRCs). Prognostic value was further evaluated in a publicly available dataset of clinically sequenced metastatic CRCs (MSK-IMPACT; n=934 MSS). Multivariable Cox proportional hazards analyses with clinicopathological parameters were performed for locoregional (stage I-III) and metastatic (stage IV and recurrent) cancers separately. Prevalent co-mutations were detected in 23 unique gene pairs, 20 of which included APC, TP53, KRAS and/or PIK3CA. Several co-mutations involving APC were associated with good overall survival in locoregional CRC, including APC-TCF7L2 (multivariable HR: 0.49, 95% CI 0.27-0.89). This co-mutation was prognostic also in metastatic cancers (multivariable HR: 0.49 and 0.37, 95% CI: 0.24-0.98 and 0.17-0.82 in the Swedish and MSK cohorts, respectively). APC-SOX9 co-mutations were mutually exclusive with APC-TCF7L2, and the co-mutations combined had stronger prognostic associations than APC alone in both metastatic cohorts. BRAF p.V600E-RNF43 co-mutations were associated with poor overall and recurrence-free survival in locoregional CRC (multivariable HR: 4.13 and 3.2, 95% CI: 1.78-9.54 and 1.53-8.04, respectively). We report a genome-wide evaluation of co-occurring mutations in MSS CRCs, and suggest that co-mutations can improve the prognostic stratification compared to single mutations alone.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"80 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697101","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":"Single-cell RNA sequencing reveals immune microenvironment niche transitions during the invasive and metastatic processes of ground-glass nodules and part-solid nodules in lung adenocarcinoma","authors":"Yi-Feng Ren, Qiong Ma, Xiao Zeng, Chun-Xia Huang, Jia-Li Ren, Fang Li, Jia-Jing Tong, Jia-Wei He, Yang Zhong, Shi-Yan Tan, Hua Jiang, Long-Fei Zhang, Heng-Zhou Lai, Ping Xiao, Xiang Zhuang, Peng Wu, Li-Ting You, Wei Shi, Xi Fu, Chuan Zheng, Feng-Ming You","doi":"10.1186/s12943-024-02177-7","DOIUrl":"https://doi.org/10.1186/s12943-024-02177-7","url":null,"abstract":"Radiographically, ground-glass nodules (GGN) and part-solid nodules (PSN) in lung adenocarcinoma (LUAD) have significant heterogeneity in their clinical manifestations, biological characteristics, and prognosis. This study aimed to explore the heterogeneity of LUAD in different radiological phenotypes and associated factors influencing tumor evolution. We performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from eight and seven cases of GGN– and PSN–LUAD, respectively, at different disease stages, including minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC), and metastatic lung cancer (MLC). Additionally, we analyzed adjacent normal tissues from four cases. Immunohistochemistry, multiplex immunofluorescence, and external scRNA-seq data were employed to confirm the expression of signature genes as well as the distribution patterns of CXCL9 + TAMs and TREM2 + TAMs. A LUAD mouse model was generated using gene editing, organoid culture, and orthotopic transplantation techniques, and comprehensive analyses such as histopathology, RNA sequencing, and Western blotting were performed to validate key pathways. Diverse cellular compositions were observed in the tumor microenvironment (TME) during GGN– and PSN–LUAD invasion and metastasis. Notably, CXCL9 + and TREM2 + tumor-associated macrophages (TAMs) exhibited the most significant enrichment changes. It was found that GGN–LUAD exhibited a stronger immune response than PSN–LUAD, with increased interaction between CXCL9 + TAMs and CD8 + tissue-resident memory T cells during invasion stage (MIA–IAC). Conversely, greater interactions between TREM2 + TAMs and tumor cells were observed in PSN–LUAD during the MLC stage. Additionally, TREM2 + TAMs were found to differentiate into TREM2 + /SPP1 + and TREM2 + /SPP1– TAMs at different stages, which promotes tumor progression. This study also emphasizes that during the transdifferentiation process of GGN– and PSN–LUAD, IFN-γ activates the STAT1 signaling pathway to regulate the activation of CXCL9 + TAMs, and further recruiting CD8 + Trm cells and activating T cells through MHC class I antigen presentation. The role of the IFN-γ/STAT1 pathway in the occurrence and development of LUAD was further validated by animal experiments. Our findings offer a potential therapeutic strategy to maintain a dynamic balance within the TME and improve the immunotherapy efficacy by modulating the relative proportions and functional states of CXCL9 + TAMs and TREM2 + TAMs.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"12 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690833","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":"Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer","authors":"Shan Liu, Xingda Zhang, Wenzheng Wang, Xue Li, Xue Sun, Yuqian Zhao, Qi Wang, Yingpu Li, Fangjie Hu, He Ren","doi":"10.1186/s12943-024-02165-x","DOIUrl":"https://doi.org/10.1186/s12943-024-02165-x","url":null,"abstract":"Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving metabolic resistance in both primary and metastatic breast cancer, and how the unique metabolic environments in metastatic sites further complicate treatment. By targeting distinct metabolic vulnerabilities at both the primary and metastatic stages, new strategies could improve the efficacy of existing therapies and provide better outcomes for breast cancer patients.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"74 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678940","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":"Myofibroblast-derived extracellular vesicles facilitate cancer stemness of hepatocellular carcinoma via transferring ITGA5 to tumor cells","authors":"Yang Xiao, Ping Tao, Keke Zhang, Liuyan Chen, Jinyu Lv, Zhiwei Chen, Lu He, Hongling Jia, Jian Sun, Mingrong Cao, Jian Hong, Chen Qu","doi":"10.1186/s12943-024-02170-0","DOIUrl":"https://doi.org/10.1186/s12943-024-02170-0","url":null,"abstract":"Myofibroblasts constitute a significant component of the tumor microenvironment (TME) and play a pivotal role in the progression of hepatocellular carcinoma (HCC). Integrin α5 (ITGA5) is a crucial regulator in myofibroblasts of malignant tumors. Therefore, the potential of ITGA5 as a novel target for the therapeutic strategy of HCC should be investigated. Digital scanning and analysis of the HCC tissue microarray were performed to locate the distribution of ITGA5 and conduct the prognosis analysis. CRISPR Cas9-mediated ITGA5 knockout was performed to establish the ITGA5-KO myofibroblast cell line. Extracellular vesicles (EVs) derived from LX2 were extracted for the treatment of HCC cells. Subsequently, the sphere-forming ability and the stemness markers expression of the treated HCC cells were examined. An orthotopic HCC mouse model with fibrotic injury was constructed to test the outcomes of ITGA5-targeting therapy and its efficacy in the programmed death-ligand 1 (PD-L1) treatment. Co-immunoprecipitation/mass spectrometry and transcriptome data were integrated to delve into the mechanism. The tissue microarray results revealed that ITGA5 was highly enriched in the stromal myofibroblasts of HCC tissues and contributed to enhanced tumor progression and poor prognosis. Notably, ITGA5 transmission via extracellular vesicles (EVs) from myofibroblasts to HCC cells induced the acquisition of cancer stem cell-like properties. Mechanistically, ITGA5 directly bind to YES1, facilitating the activation of YES1 and its downstream pathways, thereby enhancing the stemness of HCC cells. Furthermore, the blockade of ITGA5 impeded tumor progression driven by ITGA5+ myofibroblasts and enhanced the efficacy of treatment with PD-L1 in a mouse model of HCC. Our findings elucidated a novel mechanism by which the EV-mediated transfer of ITGA5 from myofibroblasts to tumor cells augmented HCC stemness. ITGA5-targeting therapy helped prevent the progression of HCC and improved the efficacy of PD-L1 treatment. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"73 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678556","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 mitochondria: restoring the antitumor efficacy of exhausted T cells","authors":"Mei-Qi Yang, Shu-Ling Zhang, Li Sun, Le-Tian Huang, Jing Yu, Jie-Hui Zhang, Yuan Tian, Cheng-Bo Han, Jie-Tao Ma","doi":"10.1186/s12943-024-02175-9","DOIUrl":"https://doi.org/10.1186/s12943-024-02175-9","url":null,"abstract":"Immune checkpoint blockade therapy has revolutionized cancer treatment, but resistance remains prevalent, often due to dysfunctional tumor-infiltrating lymphocytes. A key contributor to this dysfunction is mitochondrial dysfunction, characterized by defective oxidative phosphorylation, impaired adaptation, and depolarization, which promotes T cell exhaustion and severely compromises antitumor efficacy. This review summarizes recent advances in restoring the function of exhausted T cells through mitochondria-targeted strategies, such as metabolic remodeling, enhanced biogenesis, and regulation of antioxidant and reactive oxygen species, with the aim of reversing the state of T cell exhaustion and improving the response to immunotherapy. A deeper understanding of the role of mitochondria in T cell exhaustion lays the foundation for the development of novel mitochondria-targeted therapies and opens a new chapter in cancer immunotherapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"641 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670670","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":"Stool and blood biomarkers for colorectal cancer management: an update on screening and disease monitoring.","authors":"Alessandro Mannucci, Ajay Goel","doi":"10.1186/s12943-024-02174-w","DOIUrl":"10.1186/s12943-024-02174-w","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers have revolutionized the management of colorectal cancer (CRC), facilitating early detection, prevention, personalized treatment, and minimal residual disease (MRD) monitoring. This review explores current CRC screening strategies and emerging biomarker applications.</p><p><strong>Main body: </strong>We summarize the landscape of non-invasive CRC screening and MRD detection strategies, discuss the limitations of the current approaches, and highlight the promising potential of novel biomarker solutions. The fecal immunochemical test remained the cornerstone of CRC screening, but its sensitivity has been improved by assays that combined its performance with other stool analytes. However, their sensitivity for advanced adenomas and the patient compliance both remain suboptimal. Blood-based tests promise to increase compliance but require further refinement to compete with stool-based biomarker tests. The ideal scenario involves leveraging blood tests to increase screening participation, and simultaneously promote stool- and endoscopy-based screening among those who are compliant. Once solely reliant on upfront surgery followed by stage and pathology-driven adjuvant chemotherapy, the treatment of stage II and III colon cancer has undergone a revolutionary transformation with the advent of MRD testing after surgery. A decade ago, the concept of using a post-surgical test instead of stage and pathology to determine the need for adjuvant chemotherapy was disruptive. Today, a blood test may be more informative of the need for chemotherapy than the stage at diagnosis.</p><p><strong>Conclusion: </strong>Biomarker research is not just improving, but bringing a transformative change to CRC clinical management. Early detection is not just getting better, but improving thanks to a multi-modality approach, and personalized treatment plans are not just becoming a reality, but a promising future with MRD testing.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":"259"},"PeriodicalIF":27.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the predictive and immunomodulatory potential of transient receptor potential melastatin family-related CCNE1 in pan-cancer.","authors":"Nan Zhang, Hao Zhang, Shuyu Li, Wantao Wu, Peng Luo, Zaoqu Liu, Yu Chen, Zhiwei Xia, Chenshen Huang, Quan Cheng","doi":"10.1186/s12943-024-02169-7","DOIUrl":"10.1186/s12943-024-02169-7","url":null,"abstract":"<p><p>Millions of new cases of cancer are diagnosed worldwide each year, making it a serious public health concern. Developments in customized therapy and early detection have significantly enhanced treatment for and results from cancer. Therefore, it is important to investigate new molecular biomarkers. In this study, we created an efficient transient receptor potential melastatin (TRPM) family members-related TRPM-Score for 17 solid tumors. CCNE1, produced from TRPM-Score, was found to be an exceptional biomarker through several sophisticated machine learning and deep learning computational techniques. TRPM-Score and CCNE1 immunotherapeutic prediction, immunological characteristics, and predictive value were thoroughly assessed. In most cancer types, CCNE1 was a substantially dangerous marker. Additional in vitro tests validated CCNE1's immunomodulatory properties, demonstrating that silencing impeded macrophage movement and decreased PD-L1 expression. Additionally, CCNE1 may accurately predict responses to cancer immunotherapy. These findings indicate that the TRPM family-particularly CCNE1, which is associated with TRPM-is a significant player in the pan-cancer domain and can be utilized as a therapeutic target and prognostic biomarkers, especially in immuno-oncology. The thorough characterization of the TRPM family and the discovery of CCNE1 as a crucial downstream effector mark important developments in our comprehension of pan-cancer biology.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":"258"},"PeriodicalIF":27.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cuproptosis, ferroptosis and PANoptosis in tumor immune microenvironment remodeling and immunotherapy: culprits or new hope.","authors":"Xiaojie Zhang, Bufu Tang, Jinhua Luo, Yang Yang, Qiaoyou Weng, Shiji Fang, Zhongwei Zhao, Jianfei Tu, Minjiang Chen, Jiansong Ji","doi":"10.1186/s12943-024-02130-8","DOIUrl":"10.1186/s12943-024-02130-8","url":null,"abstract":"<p><p>Normal life requires cell division to produce new cells, but cell death is necessary to maintain balance. Dysregulation of cell death can lead to the survival and proliferation of abnormal cells, promoting tumor development. Unlike apoptosis, necrosis, and autophagy, the newly recognized forms of regulated cell death (RCD) cuproptosis, ferroptosis, and PANoptosis provide novel therapeutic strategies for tumor treatment. Increasing research indicates that the death of tumor and immune cells mediated by these newly discovered forms of cell death can regulate the tumor microenvironment (TME) and influence the effectiveness of tumor immunotherapy. This review primarily elucidates the molecular mechanisms of cuproptosis, ferroptosis, and PANoptosis and their complex effects on tumor cells and the TME. This review also summarizes the exploration of nanoparticle applications in tumor therapy based on in vivo and in vitro evidence derived from the induction or inhibition of these new RCD pathways.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":"255"},"PeriodicalIF":27.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}