Cancer Cell International最新文献

{"title":"Elucidating the dynamic tumor microenvironment through deep transcriptomic analysis and therapeutic implication of MRE11 expression patterns in hepatocellular carcinoma.","authors":"Ruiqiu Chen, Chaohui Xiao, Zizheng Wang, Guineng Zeng, Shaoming Song, Gong Zhang, Lin Zhu, Penghui Yang, Rong Liu","doi":"10.1186/s12935-025-03931-7","DOIUrl":"10.1186/s12935-025-03931-7","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to explore the dynamic tumor microenvironment of hepatocellular carcinoma (HCC) through deep transcriptomic analysis and to identify key regulatory genes, among which MRE11 was further validated for its immunomodulatory and prognostic significance.</p><p><strong>Methods: </strong>We performed Summary-data-based Mendelian Randomization (SMR) analysis to identify genes causally associated with HCC and intersected these with DNA damage repair (DDR) genes, leading to the identification of MRE11. A comprehensive evaluation of MRE11 expression in HCC was conducted using transcriptomic data analysis. We collected data from 92 HCC patient samples and validated MRE11 expression differences in HCC tissues through qPCR, immunohistochemistry, and Western blotting. Publicly available single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics were utilized to explore MRE11's dynamic mechanisms in the tumor microenvironment (TME) of both primary and post-immunotherapy cases. We also screened for differentially expressed genes and constructed a robust HCC prognosis model using 101 machine-learning algorithms.</p><p><strong>Results: </strong>Our results demonstrated that high MRE11 expression is strongly associated with poor prognosis in HCC. In the primary TME, MRE11 regulates immune responses, facilitating immune evasion. Single-cell analysis revealed significant tumor heterogeneity in MRE11 high-expression groups, particularly in macrophages and malignant cells, where MRE11 regulates immune evasion and tumor progression via the cGAS-STING pathway and HGF-MET axis. Under immunotherapy, high MRE11 expression facilitated epithelial-mesenchymal transition (EMT) and extensive remodeling of the TME. Furthermore, MRE11 dynamically enhanced macrophage regulation, exhibiting immunosuppressive and tumor-invasive features. Finally, our prognostic model exhibited strong predictive accuracy across multiple datasets.</p><p><strong>Conclusion: </strong>High MRE11 expression is crucial in regulating the immune microenvironment in HCC, fostering immune evasion and driving tumor progression. MRE11 emerges as a promising biomarker for HCC diagnosis and a potential target for personalized immunotherapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"311"},"PeriodicalIF":6.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The endoplasmic reticulum stress-ferroptosis reciprocal signaling orchestrates anti-tumor effect of anlotinib in anaplastic thyroid cancer.","authors":"Yehao Guo, Juyong Liang, Lingling Ding, Jiajun Wu, Weidong Teng, Jiafeng Wang, Liehao Jiang, Zhuo Tan","doi":"10.1186/s12935-025-03947-z","DOIUrl":"10.1186/s12935-025-03947-z","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis-induced therapy is a promising approach for treating anaplastic thyroid carcinoma (ATC), a highly lethal form of cancer. However, the specific effects of two anti-angiogenic agents, lenvatinib and anlotinib, on ferroptosis in ATC are not well understood.</p><p><strong>Methods: </strong>Methods: To investigate the anticancer activity of lenvatinib and anlotinib in vivo, a subcutaneous tumor model was established in mice. The pharmacological effects of these agents on ATC cells were assessed using various assays, including CCK-8, colony formation, transwell, and sphere-forming assays. Angiogenesis was evaluated using a tubule formation assay. Reactive oxygen species (ROS) levels were measured by flow cytometry, and levels of ferroptosis and endoplasmic reticulum (ER) stress were determined through western blot assays. Immunohistochemistry analyses were used to profile the expression of GPX4, HO-1, PERK, and CHOP in tumor tissues.</p><p><strong>Results: </strong>Both lenvatinib and anlotinib demonstrated dose- and time-dependent inhibition of Luciferase-8505 C-induced subcutaneous tumors in mice, with anlotinib showing greater efficacy than lenvatinib. In vitro experiments revealed that while both drugs were effective at inhibiting angiogenesis, anlotinib displayed superior antitumor effects in terms of cell viability, proliferation, tumor sphere formation, migration, and invasion. Mechanistic studies indicated that anlotinib induced ROS-mediated ferroptosis through the ER stress pathway, a response not observed with lenvatinib treatment.</p><p><strong>Conclusion: </strong>Anlotinib showed superior efficacy in treating ATC compared to lenvatinib, independent of their anti-angiogenic properties. The ability of anlotinib to induce ER stress-mediated ferroptosis suggests that targeting ferroptosis may hold promise as a therapeutic strategy for ATC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"310"},"PeriodicalIF":6.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The components and regulation of the Hippo pathway and its relationships with the progression and treatment of Non-small cell lung cancer (NSCLC).","authors":"Yuheng Feng, Xueting Gan, Xuezhu Rong, Qiang Han","doi":"10.1186/s12935-025-03946-0","DOIUrl":"10.1186/s12935-025-03946-0","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"309"},"PeriodicalIF":6.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAFs exosomal miR-21-5p suppresses ferroptosis and promotes proliferation and migration in osteosarcoma.","authors":"Xiaoying Niu, Wen Tian, Yuanmeng Ke, Yifan Li, Xinxin Zhang","doi":"10.1186/s12935-025-03930-8","DOIUrl":"10.1186/s12935-025-03930-8","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma is one of the malignant tumors in children and adolescents patients. Uncontrolled and unlimited proliferation and metastasis lead to poor overall survival. CAFs play a pivotal role in the osteosarcoma tumor microenvironment, exerting significant influence on prognosis and treatment outcomes. However, there remains a need for further exploration into the intricate molecular mechanisms underlying CAFs.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was employed to characterize the microenvironment of osteosarcoma. Tissue exosomal miRNA sequencing was conducted on tumor tissues and adjacent normal tissues to screen for abnormal expression of exosomal miRNAs. WGCNA analysis was used to identify target exosomal miRNAs. The relative expression of miR-21-5p was analyzed using qRT-PCR. The proliferation rate and migration ability of tumor cells were assessed using the CCK8 and Transwell method, respectively. Exosomes derived from cells were extracted and characterized via transmission electron microscopy and NTA analysis. siRNA interference was utilized to disrupt the expression of miR-21-5p in CAFs. Experiments in vivo validated the role of exosomal miR-21-5p in promoting malignant characteristics in osteosarcoma.</p><p><strong>Results: </strong>Single-cell RNA sequencing analysis of GSE162454 revealed the crucial role of CAFs in the pathogenesis of osteosarcoma. Tissue exosomal miRNA sequencing unveiled significant differential expression of miR-21-5p. Subsequently, aberrant upregulation of exosomal miR-21-5p exhibited a strong correlation with advanced clinical stage and poor prognosis in osteosarcoma. Further experiments in vitro indicated that elevated levels of miR-21-5p significantly enhanced proliferation and migration of osteosarcoma cells by suppressing ferroptosis. Moreover, experiments in vivo validated the capacity of CAFs-derived exosomal miR-21-5p to promote tumor growth and weight, thereby demonstrating their ability to deliver miR-21-5p to osteosarcoma cells and induce proliferation and migration through inhibition of ferroptosis.</p><p><strong>Conclusions: </strong>Our findings indicate that exosomal miR-21-5p could potentially serve as a therapeutic target in osteosarcoma, providing initial evidence for further clinical investigation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"308"},"PeriodicalIF":6.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting.","authors":"Ying Chen, Xin Tang, Liran Zhu, Yi Wang, Gaopeng Li, Wulin Yang","doi":"10.1186/s12935-025-03942-4","DOIUrl":"10.1186/s12935-025-03942-4","url":null,"abstract":"<p><strong>Background: </strong>The N-formyl peptide receptor family (FPRs) is implicated in the progression of diverse cancer types, yet studies specifically exploring their roles in breast cancer remain scarce.</p><p><strong>Methods: </strong>A comprehensive analysis integrating bulk RNA-seq transcriptomics, methylomics, single-cell transcriptomics, and spatial single-cell transcriptomics data was conducted to elucidate the distinctive characteristics of FPRs in breast cancer. This study particularly focused on delineating the e xpression profiles of FPR3 across distinct breast cancer subtypes, while systematically investigating its prognostic implications and association with macrophage polarization patterns in breast cancer patients. Furthermore, molecular docking analysis was performed to screen potential therapeutic compounds targeting FPR3, providing insights into its druggability.</p><p><strong>Results: </strong>Notably, FPR3 was found to be highly expressed in macrophages within breast cancer tissues, with a notably elevated level in HER2-positive and triple-negative breast cancer (TNBC) subtypes, both of which are associated with poor prognosis. FPR3 expression inversely correlates with promoter methylation levels. Further analysis of pan-cancer immune infiltration patterns uncovered a striking association between FPR3 and macrophage infiltration, as well as their polarization status. Knockdown of FPR3 expression in macrophages markedly enhanced the expression of IL6, TNF-α, and TGF-β, while significantly reducing IL10 levels, indicative of a shift towards an M1-like macrophage phenotype. Through computational molecular docking analyses, Otamixaban and Rivaroxaban emerged as promising candidate inhibitors of FPR3.</p><p><strong>Conclusions: </strong>These findings underscore the profound infiltration of FPR3 + macrophages in breast cancer patients with adverse prognoses, highlighting FPR3 as a potential therapeutic target for intervening breast cancer aggressiveness.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"306"},"PeriodicalIF":6.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxypalmatine promotes apoptosis and protective autophagy in lung cancer cells via the PI3K/AKT pathway.","authors":"Ge Qiao, Zhanghao Huang, Youlang Zhou, Jiahai Shi","doi":"10.1186/s12935-025-03939-z","DOIUrl":"10.1186/s12935-025-03939-z","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"307"},"PeriodicalIF":6.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic information.","authors":"Kokichi Miyamoto, Ryuichi Yoshida, Kazuya Yasui, Kunitoshi Shigeyasu, Kazuhiro Yoshida, Tomokazu Fuji, Kosei Takagi, Yuzo Umeda, Kazuyuki Matsumoto, Yuki Fujii, Toshiaki Takahashi, Kazuya Moriwake, Masashi Kayano, Takeyoshi Nishiyama, Yasuo Nagai, Hideki Yamamoto, Hironari Kato, Hiroshi Tazawa, Mizuki Morita, Motoyuki Otsuka, Toshiyoshi Fujiwara","doi":"10.1186/s12935-025-03894-9","DOIUrl":"10.1186/s12935-025-03894-9","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all cancers; hence, multidisciplinary treatment is essential for patients with PDAC. Although the resectability status, tumour marker, KRAS circulating tumour DNA (mutKRAS-ctDNA) mutations, and GATA binding 6 (GATA6) expression status are promising prognostic biomarkers, their effective integration before and after surgery remains unclear.</p><p><strong>Methods: </strong>In this retrospective cohort study, patients with PDAC who had undergone radical resection were enrolled, and pre- and postoperative independent factors associated with poor prognosis were identified using Cox hazard modelling. Risk stratification systems were developed using the identified prognostic factors and investigated for the ability to predict prognosis.</p><p><strong>Results: </strong>A total of 91 patients with PDAC were included (median follow-up duration, 28 months). Borderline resectable or locally advanced cancer at diagnosis, elevated carbohydrate antigen 19-9 (CA19-9) level, and mutKRAS-ctDNA-positive status were identified as independent preoperative factors associated with poor prognosis. The postoperative factors significantly associated with shorter overall survival were low GATA6 expression, elevated CA19-9 level, and mutKRAS-ctDNA-positive status. Finally, the preoperative and postoperative risk scoring systems developed using Cox modelling hazard ratio values could significantly stratify prognosis after curative resection for PDAC.</p><p><strong>Conclusion: </strong>A risk stratification system based on liquid biopsy, specialised for each phase (pre- and post-surgery), has been proven to be a useful, simple, and practical prognostic prediction clinical tool to determine the optimal multidisciplinary treatment protocol for PDAC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"305"},"PeriodicalIF":6.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on the mechanisms of CSF3R mutations in leukemogenesis and treatment strategies.","authors":"Ningxuan Wang, Xiangan Li, Chenyang She, Jun Zhang","doi":"10.1186/s12935-025-03941-5","DOIUrl":"10.1186/s12935-025-03941-5","url":null,"abstract":"<p><p>Leukemia is a malignant clonal disease originating from hematopoietic stem cells. Its pathogenesis is associated with multiple factors, including biological, physical, chemical, genetic, and other hematological diseases. Previous studies have shown that a high mutation rate (>80%) of colony-stimulating factor receptor 3 (CSF3R) is observed in chronic neutrophilic leukemia (CNL) patients, and these mutations activate downstream signaling pathways, leading to the proliferation of neutrophils. In-depth research on the CSF3R genes and their related mechanisms will help further reveal the mechanisms of leukemia development and provide potential targets for treatment. Therefore, this paper mainly focuses on the roles of colony-stimulating factor 3 (CSF3R) in hematopoiesis and the occurrence of leukemia, with particular attention to the roles of CSF3R in the JAK-STAT, PI3K-AKT, and MAPK-ERK signaling pathways.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"304"},"PeriodicalIF":6.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N7-methylguanosine (m7G) modification in breast cancer: clinical significances and molecular mechanisms.","authors":"Tianyao Yang, Chunyan Chen, Fangfang Wang, Lan Yue","doi":"10.1186/s12935-025-03859-y","DOIUrl":"10.1186/s12935-025-03859-y","url":null,"abstract":"<p><p>The therapeutic strategies for advanced breast cancer (BC) continue to present significant challenges. Consequently, the implementation of precise diagnostic biomarkers and prognostic targets is essential for effective BC management. Recently, N7-methylguanosine (m7G) modification has garnered considerable attention in the context of various cancer types. In this study, we conducted a comprehensive literature review to explore the potential role of m7G in the tumorigenesis of BC. Analysis of thirteen relevant studies revealed that m7G methyltransferases were usually aberrantly expressed in BC, including TNBC and breast invasive carcinoma. m7G modifications in mRNA, tRNA, and rRNA can ultimately affect the expression of target genes (i.e., m7G regulators [e.g., METTL1/WDR4], m7G-associated genes [e.g. P27 and AGO2], m7G-related lncRNAs [e.g., LINC01871 and LINC00115], and m7G-related miRNAs [e.g. miR-7 and miR-139]) and regulate BC-related biological functions. These novel insights indicate that m7G modification and its regulators hold significant potential for future clinical applications in the diagnosis and treatment of BC. In the future, how to apply m7G modifications to identify the implementation of clinically personalized BC treatment needs to be further explored.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"303"},"PeriodicalIF":6.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme oxygenase-1 leads to cisplatin resistance in nasopharyngeal carcinoma by reducing oxidative stress and ferroptosis.","authors":"Zhongqiang Cheng, Lixian Huang, Yanshu Zhang, Kaiyue Yue, Shunmo Jia, Zhijie Fang, Zhiqiang Lin","doi":"10.1186/s12935-025-03908-6","DOIUrl":"10.1186/s12935-025-03908-6","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal carcinoma (NPC) is a malignancy with high a mortality rate. This study investigates the impact of heme oxygenase-1 (HO-1) in cisplatin (CDDP) resistance in NPC.</p><p><strong>Methods: </strong>The time-dependent effect of CDDP on two NPC cell lines (HK1 and C666-1) were investigated. CDDP-resistant cells were established by exposing the parental cells to increasing concentrations of CDDP. Parental cells received treatment of the HO-1 inducer Hemin while resistant cells received treatment of the HO-1 inhibitor ZnPP to explore the influence of HO-1 activity on CDDP resistance in NPC cell lines. Erastin was used to verify the effect of ferroptosis on CDDP sensitivity in cells. Parallel settings were performed in mouse xenograft tumor models for in vivo validation.</p><p><strong>Results: </strong>CDDP time-dependently reduced growth and mobility of NPC cells within the initial 48 h, but the cytotoxicity was no longer significantly enhanced afterward. HO-1 was upregulated in cells after CDDP treatment, showing correlation with acquired CDDP resistance. Inducing HO-1 activity in parental cells protected cells from oxidative damage, apoptosis, and ferroptosis, while suppressing HO-1 activity using ZnPP restored the therapeutic efficacy of CDDP in drug resistant cells. Moreover, the Erastin treatment also restored the cytotoxicity of CDDP to the resistant cells. In mice bearing xenograft tumors, treatment with either ZnPP or Erastin weakened the growth and weight of tumors.</p><p><strong>Conclusion: </strong>This work suggests that HO-1 is pertinent to acquired CDDP resistance in NPC cells by suppressing oxidative stress and ferroptosis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"302"},"PeriodicalIF":6.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}