Cancer research最新文献

{"title":"From Harmony to Discord: Multicellular Coordination in Tissues and Its Rewiring in Cancer.","authors":"Merve Dede,Vakul Mohanty,Ken Chen","doi":"10.1158/0008-5472.can-25-3155","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-3155","url":null,"abstract":"Tissue function emerges from coordinated interactions among diverse cell types, but how these interactions are structured and rewired in disease remains unclear. In a recent study, Shi and colleagues introduce CoVarNet, a computational framework that maps reproducible multicellular modules (CMs) across 35 human tissues using single-cell and spatial transcriptomics. These CMs, spanning immune, stromal, and endothelial cells, exhibit functional organization across tissue systems and dynamically respond to biological transitions such as aging and menopause. Importantly, cancer progression is marked by a breakdown of tissue-specific CMs and the emergence of a convergent cancer-associated ecosystem, cCM02. This rewiring reflects a fundamental reorganization of tissue architecture during malignancy and provides new opportunities for diagnostics and therapeutic targeting. The study signifies a conceptual advance from cell-centric to ecosystem-level biology and offers a generalizable framework for integrating multimodal data to dissect tissue-level coordination. Here, we discuss how CoVarNet redefines our understanding of tissue organization, its translational implications in oncology, and unresolved questions in modular tissue biology.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"111 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684045","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":"Prostate Cancer Cells Secrete PD-1 in Exosomes to Enhance Myeloid-Derived Suppressor Cell Activity and Promote Tumor Immune Evasion.","authors":"Jie Zhang,Weiwu Chen,Chen Zhang,Qian He,Xudong Wang,Jiayu Han,Peng Gao,Kunyu Wang,Haoze Xie,Feng Gao,Yining Guo,Wenhao Guo,Haofei Jiang,Jing Le,Ruichen Zang,Sisi Mo,Haobo Fan,Xiaoxiao Zhu,Xinrong Jiang,Fengbin Gao,Yanlan Yu,Guoqing Ding,Yicheng Chen","doi":"10.1158/0008-5472.can-24-3748","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-3748","url":null,"abstract":"PD-1 restrains effective killing of cancer cells by the immune system and is predominantly located on the surface of T cells or other immune cells. However, cancer cells also express PD-1 to varying degrees, which is commonly associated with a poor prognosis. Here, we investigated the regulation and function of PD-1 expression in prostate cancer (PCa) and revealed the impact on the tumor microenvironment. PD-1 expression in cancer cells positively correlated with Gleason grade and metastasis but negatively correlated with CD8+ T cell infiltration in PCa patients. PCa cells secreted PD-1 in exosomes that enhanced the activity of myeloid-derived suppressor cells (MDSCs) by activating JAK/STAT3 signaling. The activated MDSCs in turn reduced the infiltration of CD8+ T cells within the tumor, promoting tumor immune evasion. The ubiquitin-specific protease USP7 induced deubiquitination and elevated the abundance of PD-1 in PCa, and USP7 inhibition sensitized PCa tumors to anti-PD-1 antibody treatment. Given the modest efficacy of current immunotherapeutic approaches for PCa, strategies to inhibit the secretion of PD-1-bearing exosomes or USP7 function may emerge as promising immunostimulatory interventions for treating PCa.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"37 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684079","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":"Multi-omic Characterization of Pre- and Post-neoadjuvant Chemotherapy Treated Ovarian Cancer Reveals Mediators of Tumorigenesis and Chemotherapy Response","authors":"Mark C. Valentine, Mary M. Mullen, Emilee N. Kotnik, Matthew A. Powell, Premal H. Thaker, Carolyn K. McCourt, Lindsay M. Kuroki, Andrea R. Hagemann, Rebecca C. Arend, Alex S. Holehouse, Robi Mitra, David G. Mutch, Katherine C. Fuh","doi":"10.1158/0008-5472.can-24-3804","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-3804","url":null,"abstract":"High-grade serous ovarian cancer (HGSC) accounts for more than 200,000 deaths each year. Despite recent advances in treating HGSC with neoadjuvant chemotherapy, the majority of patients ultimately develop chemotherapy resistance. HGSC is characterized by TP53 mutations and widespread copy number alterations and occurs frequently in the setting of deleterious germline BRCA1/2 variations, but many cases lack putative driver mutations. Here, we performed whole-exome, whole-genome, and whole transcriptome sequencing along with mass spectrometry to characterize the molecular landscape of HGSC in 22 paired samples obtained before and after neoadjuvant chemotherapy. Responsiveness to chemotherapy was determined for each patient. Evidence at the DNA, RNA, and protein level revealed numerous defects in cell-cell and cell-matrix interactions as well as disruption of cell polarity and cytoskeletal regulation in HGSC, indicating that defects in epithelial integrity were present in the majority of HGSC patients. Non-responsive HGSC harbored subclones with putative survival mutations. Additionally, ineffective nonsense mediated decay resulted in the persistence of transcripts with frameshift mutations that were translated into aberrant proteins detectable in HGSC samples. Together, these findings suggest that HGSC may arise through defects in maintenance of epithelial integrity that lead to shedding of malignant cells throughout the peritoneum, and the presence of resistant subclones prior to chemotherapy may decrease the chemosensitivity of patients.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"6 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677454","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":"Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer.","authors":"Kristina Drizyte-Miller,Lars D Engstrom,Jeffrey A Klomp,Clint A Stalnecker,Addison G Stamey,Khalilah E Taylor,Mallory K Roach,Ryan Robb,Laura M Waters,Andrew Calinisan,Seamus Degan,Wen-Hsuan Chang,Xousaen M Helu,David Nguyen,Elisa Baldelli,Mariaelena Pierobon,Emanuel F Petricoin,David M Briere,Jill Hallin,James G Christensen,Kirsten L Bryant,Adrienne D Cox,Peter Olson,Channing J Der","doi":"10.1158/0008-5472.can-25-1507","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-1507","url":null,"abstract":"Protein arginine methyltransferase 5 (PRMT5) is a synthetic lethal target in MTAP-deleted (MTAP-del) cancers. The MTA-cooperative PRMT5 inhibitor BMS-986504 exhibited potent and selective anti-tumor activity in MTAP-del preclinical models and demonstrated activity in MTAP-del patients without the toxicity associated with previous PRMT5 inhibitors. Here, we focused on pancreatic ductal adenocarcinoma (PDAC), ~22% of which are MTAP-del, and demonstrated that BMS-986504 suppressed PRMT5 function and cell growth in MTAP-del cells and xenograft models. CRISPR/Cas9 loss-of-function screens implicated co-targeting KRAS as a combination strategy. Concurrent inhibition of PRMT5 and KRASG12C/D enhanced and prolonged suppression of PDAC growth. RNA-sequencing analysis revealed that PRMT5 inhibition disrupted RNA splicing of genes essential for PDAC growth. While PRMT5 and KRAS regulated distinct transcriptomes, they converged on pathways governing cancer cell growth and expression of PDAC-essential genes. These findings provide rationale for combined inhibition of PRMT5 and KRAS in MTAP-deleted/KRAS-mutant PDAC.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"66 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684106","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":"CRISPR-Drug Combinatorial Screening Identifies Effective Combination Treatments for MTAP-deleted Cancer.","authors":"Nikola Knoll,Sarah Masser,Blanka Bordas,Richard Y Ebright,Guangyan Li,Devishi Kesar,Eliana Destefanis,Nicholas Kania,Diego J Rodriguez,Jayu Jen,Sydney E Zagar,Caleb Mensah,Zixin Chen,Samuel J Moffitt,Erhumuoghene M Enakireru,Yao He,Baomou Feng,Mira K Chokshi,Cyrus Y Jin,Srivatsan Raghavan,William R Sellers,Kathleen M Mulvaney","doi":"10.1158/0008-5472.can-25-1464","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-1464","url":null,"abstract":"CDKN2A/MTAP co-deletion occurs frequently in non-small cell lung cancer and other solid tumors, including glioblastoma and pancreatic ductal adenocarcinoma. Lung cancer remains the leading cause of cancer-related mortality, and fewer than 15% of glioblastoma or pancreatic cancer patients survive 5 years, underscoring the need for more effective therapies. PRMT5 is a synthetic-lethal dependency in MTAP-null tumors and an attractive therapeutic target for CDKN2A/MTAP-deleted cancers. A new revolutionary class of inhibitors, referred to as MTA-cooperative PRMT5 inhibitors, has shown promising results in ongoing early phase clinical trials. Nonetheless, effective cancer treatment typically requires therapeutic combinations to improve response rates and defeat emergent resistant clones. Thus, we sought to determine whether perturbation of other pathways could improve the efficacy of MTA-cooperative PRMT5 inhibitors. A paralog and single gene targeting CRISPR library was used to screen MTAP-deleted cancers in the presence or absence of MTA-cooperative PRMT5 inhibitors. Loss of several genes sensitized to PRMT5 inhibition, including members of the MAPK pathway. Chemical inhibition of MAPK pathway members using KRAS, MEK, ERK, and RAF inhibitors synergized with PRMT5 inhibition to kill CDKN2A/MTAP-null, RAS-active tumors. Further, MTA-cooperative PRMT5 inhibitors combined with either KRAS or RAF inhibitors led to complete responses in vivo, emphasizing the potential benefit for patients. Lastly, cell lines resistant to KRAS inhibition were not resistant to MTA-cooperative PRMT5 inhibitors and vice versa, suggesting non-cross-reactive mechanisms of resistance. Overall, this study identifies therapeutic combinations with MTA-cooperative PRMT5 inhibitors that may offer significant benefit to patients.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"14 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684110","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":"Catch Me If You Can: Could Y Chromosome Loss Spread in Cancer?","authors":"Zihai Li","doi":"10.1158/0008-5472.can-25-3058","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-3058","url":null,"abstract":"The recent surge in studies of loss of the Y chromosome (LOY) in cancer has challenged long-standing assumptions about the Y chromosome as largely dispensable outside of sex determination and spermatogenesis. In the latest paper, the labs of Knott and Theodorescu present provocative evidence suggesting that LOY in tumor cells correlates with LOY in tumor-infiltrating immune cells and, most unexpectedly, that LOY may be \"contagious\" within the tumor microenvironment. These findings, while intriguing, demand cautious interpretation and rigorous validation. Notably, while the authors observe correlation between tumor LOY and stromal LOY, the causal mechanisms remain obscure. Moreover, the notion that LOY can be induced in non-malignant immune cells by LOY tumor cells warrants both excitement and further experimental scrutiny. Nonetheless, this study serves as a catalyst for renewed interest in the functional relevance of the Y chromosome in cancer and aging. As Darwin alluded, sexuality and its chromosomal determinants remain among biology's deepest mysteries. The current work opens a new chapter in this exploration, albeit one that must be read with both curiosity and scientific rigor.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"109 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652276","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":"Pan-Cancer Spatial Profiling Reveals Conserved Subtypes and Niches of Cancer-Associated Fibroblasts.","authors":"Hani Jieun Kim, Travis Ruan, Alexander Swarbrick","doi":"10.1158/0008-5472.CAN-25-2181","DOIUrl":"10.1158/0008-5472.CAN-25-2181","url":null,"abstract":"<p><p>Solid cancers are complex \"ecosystems\" comprised of diverse cell types and extracellular molecules, in which heterotypic interactions significantly influence disease etiology and therapeutic response. However, our current understanding of tumor microenvironments remains incomplete, hindering the development and implementation of novel tumor microenvironment-targeted drugs. To maximize cancer therapeutic development, we require a system-level understanding of the malignant, stromal, and immune states that define the tumor and determine treatment response. In their recent study, Liu and colleagues took a new approach to resolving the complexity of stromal heterogeneity. They leveraged extensive single-cell spatial multiomic datasets across various cancer types and platforms to identify four conserved spatial cancer-associated fibroblast (CAF) subtypes, classified by their spatial organization and cellular neighborhoods. Their work expands upon prior efforts to develop a CAF taxonomy, which primarily relied on single-cell RNA sequencing and yielded a multitude of classification systems. This study advances our understanding of CAF biology by establishing a link between spatial context and CAF identity across diverse tumor types. Departing from recent single-cell transcriptomic studies that employed a marker-based approach for substate identification, Liu and colleagues conducted de novo discovery of CAF subtypes using spatial neighborhood information alone. By positioning spatial organization as the defining axis of CAF heterogeneity, this research redefines CAF classification and provides a new framework for exploring the rules governing tumor ecosystems and developing novel ecosystem-based therapeutic strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":" ","pages":"2555-2557"},"PeriodicalIF":12.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172941","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":"Bacterial Therapeutics: Addressing the Affordability Gap in Cancer Therapy","authors":"Kejsi Prifti, Chiswili Yves Chabu, Koichi S. Kobayashi, Jianxun Song, Arum Han, Paul de Figueiredo","doi":"10.1158/0008-5472.can-25-0870","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-0870","url":null,"abstract":"The global cancer care burden is projected to reach $25 trillion by 2050, with the United States experiencing increasing costs from $57 billion to $209 billion. The application of expensive cellular immunotherapies (exceeding $300,000 per treatment) will exacerbate escalating cancer care costs. Bacteria-based immunotherapies are emerging as safe, lower-cost alternatives. Recent synthetic biology and artificial intelligence advances may enable the development of next-generation bacterial therapies with reduced toxicity. These systems can bypass cold chain constraints and be manufactured at &amp;lt;$10/dose, offering more than 30,000-fold cost savings compared to cell therapies. Therefore, as they evolve, bacterial therapies could transform cancer care by improving outcomes and alleviating global healthcare economic pressures.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"30 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629826","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":"Genomic and Single-Cell Analyses Characterize Patient-Derived Tumor Organoids to Enable Personalized Therapy for Head and Neck Squamous Cell Carcinoma.","authors":"Jung Hyun Um, Yueyuan Zheng, Qiong Mao, Chehyun Nam, Hua Zhao, Yoon Woo Koh, Su-Jin Shin, Young Min Park, De-Chen Lin","doi":"10.1158/0008-5472.CAN-24-2850","DOIUrl":"10.1158/0008-5472.CAN-24-2850","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) remains a significant health burden because of tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. In this study, we enrolled 31 patients with HNSCC for the establishment of patient-derived tumor organoids (PDO), which faithfully maintained the genomic features and histopathologic traits of the primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, with ex vivo drug sensitivity correlating with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor transcriptional heterogeneity (ITH) in PDOs, paralleling patient tumors. Notably, a hybrid epithelial-mesenchymal transition-like ITH program was associated with cisplatin resistance and poor patient survival. Functional analyses identified amphiregulin as a potential regulator of the hybrid epithelial-mesenchymal state. Moreover, amphiregulin contributed to cisplatin resistance via EGFR pathway activation, corroborated by clinical samples. In summary, HNSCC PDOs serve as reliable and versatile models, offer predictive insights into ITH programs and treatment responses, and uncover potential therapeutic targets for personalized medicine.</p><p><strong>Significance: </strong>Profiling of patient-derived organoids uncovers intertumoral heterogeneity and a hybrid epithelial-mesenchymal transition program conferring cisplatin resistance and highlights amphiregulin as a regulator of cellular plasticity and potential therapeutic target for HNSCC treatment.</p>","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":" ","pages":"2726-2742"},"PeriodicalIF":12.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966134","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":"FADD Activation in Hepatocellular Carcinoma Potentiates CD8+T Cell Responses and Sensitizes to Immune Checkpoint Inhibitors","authors":"Jiahuan Lu, Thomas Ting-Hei. Chan, Yun Wang, Jingya Wang, Zhewen Xiong, Jingqing Li, Yixuan Zhang, Huanyu Wang, Jintian Chen, Weiqin Yang, Jing Wang, Yalin Tu, Howard H.W. Leung, Raymond Wai Ming. Lung, Wei Kang, Man Tong, Dan Michelle. Wang, Qi-Nian Wu, Zhao-Lei Zeng, Alfred Sze Lok. Cheng, Ka-Fai To, Anthony W.H. Chan, Jingying Zhou","doi":"10.1158/0008-5472.can-24-3854","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-3854","url":null,"abstract":"Turning immunologically “cold” tumors “hot” is required for effective immune checkpoint inhibitor (ICI) treatment in hepatocellular carcinoma (HCC). Here, we identified Fas-associated death domain (FADD) as a key molecule upregulated in HCC with dense tumor-infiltrating CD8+ T cells and better response to ICIs. CRISPR-mediated knockout of Fadd in murine HCC cells led to increased tumor weights in immunocompetent, but not immunodeficient, mice. FADD deficiency also led to decreased intratumoral infiltration of CD8+ T cells and lower production of IFN-γ and TNF-ɑ. Mechanistically, phosphorylated FADD translocated into the nucleus where it interacted with Sam68 to upregulate NF-κB-induced transcription of CCL5, thereby promoting CD8+ T cell recruitment. Treatment with anti-PD-1 triggered FADD phosphorylation in ICI-sensitive tumors, which was not observed in ICI-resistant tumors. FADD activation through genetic or pharmacologic approaches overcame ICI resistance in orthotopic and spontaneous HCC mouse models in vivo. Together, these findings provide insights into combinatory immunotherapy approaches for HCC patients.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"23 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629832","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}