Molecular Carcinogenesis最新文献

{"title":"FOS-Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple-Negative Breast Cancer.","authors":"Yuxian Shu, Jun Lan, Huijing Luo, Huiying Fu, Xuhuang Xiao, Liping Yang","doi":"10.1002/mc.23834","DOIUrl":"https://doi.org/10.1002/mc.23834","url":null,"abstract":"<p><p>Radioresistance and immune evasion are interactive and crucial events leading to treatment failure and progression of human malignancies. This research studies the role of phospholipase C beta 1 (PLCB1) in these events in triple-negative breast cancer (TNBC) and the regulatory mechanism. PLCB1 was bioinformatically predicted as a dysregulated gene potentially linked to radioresistance in TNBC. Parental TNBC cell lines were exposed to fractionated radiation for 6 weeks. PLCB1 expression was decreased in the first 2 weeks but gradually increased from Week 3. PLCB1 knockdown increased the radiosensitivity of the cells, as manifested by a decreased half-inhibitory dose of irradiation, reduced cell proliferation, apoptosis resistance, mobility, and tumorigenesis in mice. The FOS transcription factor promoted PLCB1 transcription and activated the PI3K/AKT signaling. Knockdown of FOS similarly reduced radioresistance and T cells-mediated immune evasion. However, the radiosensitivity of TNBC cells and the antitumor effects of CD8⁺ T cells could be affected by a PI3K/AKT activator or by the PLCB1 upregulation. The PLCB1 or FOS knockdown also suppressed radioresistance and tumorigenesis of the TNBC cells in mice. In conclusion, FOS-mediated PLCB1 induces radioresistance and weakens the antitumor effects of CD8⁺ T cells in TNBC by activating the PI3K/AKT signaling pathway.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504548","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":"FAM20C Promotes Papillary Thyroid Cancer Proliferation and Metastasis via Epithelial-Mesenchymal Transition.","authors":"Bangyi Lin, Xuejuan Jiang, Adheesh Bhandari, Qi Chen, Yin Pan","doi":"10.1002/mc.23833","DOIUrl":"10.1002/mc.23833","url":null,"abstract":"<p><p>Thyroid cancer (TC) is the prevailing malignancy that impacts the endocrine system, accounting for 1% of all recently diagnosed malignancies in humans. The incidence of TC has been continuously increasing, which can be attributed to advancements in clinical diagnostic technology. However, the mechanisms behind the development of TC are still not well understood. TC is classified into four pathological forms: medullary thyroid cancer, papillary thyroid cancer (PTC), follicular thyroid cancer, and poorly differentiated TC. PTC constitutes more than 80% of all TC cases globally. Current research indicates that complex genetic and cellular processes could be responsible for the growth and spread of TC. Next-generation sequencing (RNA-seq) of 79 PTC samples and their corresponding normal thyroid tissues was performed to investigate the molecular mechanisms of PTC. An analysis of RNA-seq data from a local cohort from The Cancer Genome Atlas (TCGA) revealed that, compared with normal tissues, PTC tissues presented elevated FAM20C expression levels. In vitro, the function of FAM20C was validated with small interfering RNA (siRNA). Gene set enrichment analysis (GSEA) revealed the pathways influenced by FAM20C. A western blot experiment was used to investigate protein expression levels associated with epithelial‒mesenchymal transition (EMT). In conclusion, by regulating EMT, FAM20C facilitates PTC cell proliferation and metastasis.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470482","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":"Sohlh2 Promotes the Progression of Hepatocellular Carcinoma via TGM2-Mediated Autophagy.","authors":"Xuyue Liu, Ruihong Zhang, Lanlan Liu, Sujuan Zhi, Xiaoning Feng, Ying Shen, Liyan Wang, Qi Zhang, Yanru Chen, Jing Hao","doi":"10.1002/mc.23832","DOIUrl":"10.1002/mc.23832","url":null,"abstract":"<p><p>Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for 85% of liver cancer-related deaths. Autophagy controls HCC cell growth, invasion, metastasis, drug resistance, and stemness. Spermatogenesis and oogenesis basic helix-loop-helix transcription factor 2 (Sohlh2) can bind to the E-boxes in the promoter regions of target genes, which are involved in multiple neoplasms. In this study, Sohlh2 was highly expressed in HCC tissues and was related to poor prognosis. Moreover, Sohlh2 overexpression promoted the proliferation, migration, invasion, and metastasis of HCC cells in vivo and in vitro. However, Sohlh2 silencing inhibited proliferation, migration, invasion, and metastasis of HCC cells in vivo and in vitro. Mechanistically, Sohlh2 could bind to the promoter of TGM2 and enhance its transcriptional activity, thereby enhancing the autophagy of HCC cells. Furthermore, Sohlh2 protein levels were positively associated with TGM2 expression in HCC tissues. Taken together, these results demonstrate that Sohlh2 can promote HCC progression via TGM2-mediated autophagy, implying that Sohlh2 is a promising candidate for HCC treatment.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470487","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":"Energy Metabolic Profile in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Preliminary Landscape of Warburg Effect in Oral Cancer.","authors":"Francisca Aurina Gonçalves, Leonardo da Silva Bittencourt, Silvia Barbosa, Leonardo Francisco Diel, Lisiane Bernardi, Cristiane Matte, Marcelo Lazzaron Lamers","doi":"10.1002/mc.23831","DOIUrl":"https://doi.org/10.1002/mc.23831","url":null,"abstract":"<p><p>We hypothesized that cell energy metabolic profiles correlate with normal, dysplastic, and tumor cell/tissue statuses and may be indicators of aggressiveness in oral squamous cell carcinoma (OSCC) cells. The energy-related proteins that were differentially expressed in human OSCC fragments (n = 3) and their adjacent epithelial tissue (TAE) were verified using mass spectrometry (MS). Immunohistochemistry for 4-hydroxynonenal (4-HNE) was performed to evaluate the oxidative stress patterns in OSCC (n = 10), epithelial dysplasia (n = 9), and normal epithelial (n = 4) biopsies. The metabolic energy profile of OSCC aggressiveness was investigated in human OSCC cell lines with different levels of epithelial-mesenchymal transition proteins. The genes associated with the proteins found by MS in this study were analyzed using survival analysis (OS), whereas the genes associated with a poorer prognosis were analyzed using context-specific expression, Gene Ontology (GO) and Cancer Hallmarks for function enrichment analysis. The rationale for all experimental approach was to investigate whether the variation in energy metabolism profile accompanies the different phenotypes (from epithelial to mesenchymal) during the epithelial-mesenchymal transition. All OSCC fragments exhibited an increase in glycolysis-related proteins and a decrease in mitochondrial activity compared to the TAE region (p < 0.05), probably due to the downregulation of pyruvate dehydrogenase and antioxidant proteins. Additionally, the OSCC cell lines with a mesenchymal profile (SCC4, SCC9, and SCC25) had a lower mitochondrial mass and membrane potential and generated lower levels of reactive oxygen and nitrogen species than the TAE region. When we analyzed 4-HNE, the reactive species levels were increased in the epithelial regions of OSCC and potentially malignant lesions. A decrease in the levels of 4-HNE/reactive species was observed in the connective tissue underlying the dysplastic regions and the OSCC invasion zone. Based on this scenario, aggressive OSCC is associated with high glycolytic and oxidative metabolism and low mitochondrial and antioxidant activities, which vary according to the differentiation level of the tumor cells and the stage of carcinogenesis.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470481","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":"Hepatitis B Virus X Protein Contributes to Hepatocellular Carcinoma via Upregulation of KIAA1429 Methyltransferase and mRNA m6A Hypermethylation of HSPG2/Perlecan.","authors":"Enakshi Sivasudhan, Jingxian Zhou, Jiongming Ma, Yuanyuan Wang, Siying Liu, Faez Iqbal Khan, Zhiliang Lu, Jia Meng, Neil Blake, Rong Rong","doi":"10.1002/mc.23830","DOIUrl":"https://doi.org/10.1002/mc.23830","url":null,"abstract":"<p><p>Chronic hepatitis B virus (HBV) remains to be the most common risk factor of hepatocellular carcinoma (HCC). While previous work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx)-mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV-encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx-expressing stable HCC cell lines, Huh7-HBx and HepG2-HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA-seq and MeRIP-seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2/Perlecan and promotes tumourigenesis. Furthermore, we observed a potential interaction between KIAA1429 and HSPG2 in HCC liver cancer cells and demands further investigation.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470484","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":"Integrating Multi-Omics Data to Uncover Prostate Tissue DNA Methylation Biomarkers and Target Genes for Prostate Cancer Risk.","authors":"Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu","doi":"10.1002/mc.23828","DOIUrl":"https://doi.org/10.1002/mc.23828","url":null,"abstract":"<p><p>Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. We observed significant associations for 3879 CpG sites, including 926 at novel genomic loci. Among them, DNAm levels of 80 CpG sites located at novel loci are significantly associated with expression levels of 45 neighboring genes in normal prostate tissue. Of these genes, 11 further exhibit significant associations with PCa risk for their predicted expression levels in prostate tissue. Intriguingly, a total of 31 CpG sites demonstrate consistent association patterns across the methylation-gene expression-PCa risk pathway. Our findings suggest that specific CpG sites may be related to PCa risk by modulating the expression of nearby target genes.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470485","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":"microRNA-2117 Negatively Regulates Liver Cancer Stem Cells Expansion and Chemoresistance Via Targeting SOX2.","authors":"Qing Xia, Guanghua Liu, Wenbo Lin, Jin Zhang","doi":"10.1002/mc.23824","DOIUrl":"https://doi.org/10.1002/mc.23824","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are involved in the regulation of tumor initiation, progression, recurrence, and chemoresistance. However, the role of microRNAs (miRNAs) in liver CSCs has not been fully understood. Here we show that miR-2117 is downregulated in liver CSCs and predicts the poor prognosis of hepatocellular carcinoma (HCC) patients. Biofunction studies found that knockdown miR-2117 facilitates liver CSCs self-renewal and tumorigenesis. Conversely, forced miR-2117 expression suppresses liver CSCs self-renewal and tumorigenesis. Mechanistically, we find that transcription factor SOX2 is required for miR-2117-mediated liver CSCs expansion. The correlation between miR-2117 and SOX2 was confirmed in human HCC tissues. More importantly, miR-2117 overexpression HCC cells are more sensitive to CDDP treatment. Analysis of patients' cohort further demonstrates that miR-2117 may predict transcatheter arterial chemoembolization benefits in HCC patients. Our findings revealed the crucial role of miR-2117 in liver CSCs expansion, rendering miR-2117 as an optimal therapeutic target for HCC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470486","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":"Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome-Wide Association Study.","authors":"Da-Tian Bau, Ting-Yuan Liu, Jai-Sing Yang, William Tzu-Liang Chen, Chia-Wen Tsai, Wen-Shin Chang, Tao-Wei Ke, Chi-Chou Liao, Yu-Chia Chen, Yen-Ting Chang, Fuu-Jen Tsai","doi":"10.1002/mc.23823","DOIUrl":"10.1002/mc.23823","url":null,"abstract":"<p><p>We conducted the first genome-wide association study (GWAS) of colorectal cancer (CRC) in Taiwan with 5342 cases and 61,015 controls. Ninety-two SNPs in three genomic regions reached genome-wide significance (p < 5 × 10^-8). The lead SNPs in these three regions were: rs12778523 (OR = 1.18, 95% CI, 1.15-1.23, p = 4.51 × 10^-13), an intergenic SNP between RNA5SP299 and LINC02676 at chromosome 10p14; rs647161 (OR = 1.14, 95% CI, 1.09-1.19, p = 2.21 × 10^-9), an intronic SNP in PITX1 at 5q31.1, and rs10427139 (OR = 1.20, 95% CI, 1.14-1.28, p = 3.62 × 10^-9), an intronic SNP in GPATCH1 at 19q13.1. We further validated CRC susceptibility SNPs previously identified through GWAS in other populations. A total of 61 CRC susceptibility SNPs were confirmed in Taiwanese. The top validated putative CRC susceptibility genes included: POU2AF2, HAO1, LAMC1, EIF3H, BMP2, ZMIZ1, BMP4, POLD3, CDKN1A, PREX1, CDKN2B, CDH1, and LRIG1. The top enriched pathways included TGF-β signaling, BMP signaling, extracellular matrix organization, DNA repair, and cell cycle control. We could not validate SNPs in HLA-G at 6p22.1 and in NOTCH4 at 6p21.32. We generated a weighted genetic risk score (GRS) using the 61 SNPs and constructed receiver operating characteristic (ROC) curves using the GRS to predict CRC. The area under the ROC curve (AUC) was 0.589 for GRS alone and 0.645 for GRS, sex, and age. These susceptibility SNPs and genes provide important insights into the molecular mechanisms of CRC development and help identify high-risk individuals for CRC in Taiwan.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400806","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":"Functional Analysis of BARD1 Missense Variants on Homology-Directed Repair in Ovarian and Breast Cancers.","authors":"Wenjing Li, Guansheng Chen, Yongjun Wang, Yuening Jiang, Nanlin Wu, Mingjie Hu, Taju Wu, Wei Yue","doi":"10.1002/mc.23829","DOIUrl":"https://doi.org/10.1002/mc.23829","url":null,"abstract":"<p><p>Women with germline BRCA1 mutations face an increased risk of developing breast and ovarian cancers. BARD1 (BRCA1 associated RING domain 1) is an essential heterodimeric partner of BRCA1, and mutations in BARD1 are also associated with these cancers. While BARD1 mutations are recognized for their cancer susceptibility, the exact roles of numerous BARD1 missense mutations remain unclear. In this study, we conducted functional assays to assess the homology-directed DNA repair (HDR) activity of all BARD1 missense substitutions identified in 55 breast and ovarian cancer samples, using the real-world data from the COSMIC and cBioPortal databases. Seven BARD1 variants (V85M, P187A, G491R, R565C, P669L, T719R, and Q730L) were confirmed to impair DNA damage repair. Furthermore, cells harboring these BARD1 variants exhibited increased sensitivity to the chemotherapeutic drugs, cisplatin, and olaparib, compared to cells expressing wild-type BARD1. These findings collectively suggest that these seven missense BARD1 variants are likely pathogenic and may respond well to cisplatin-olaparib combination therapy. This study not only enhances our understanding of BARD1's role in DNA damage repair but also offers valuable insights into predicting therapy responses in patients with specific BARD1 missense mutations.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470483","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":"ALKBH5-Mediated m⁶A Modification of XBP1 Facilitates NSCLC Progression Through the IL-6-JAK-STAT3 Pathway.","authors":"Hengxing Liang, Chunmin Zhang, Minxin Hu, Fang Hu, Saihui Wang, Wei Wei, Wen Hu","doi":"10.1002/mc.23826","DOIUrl":"https://doi.org/10.1002/mc.23826","url":null,"abstract":"<p><p>The X-box-binding protein 1 (XBP1) is an important transcription factor during endoplasmic reticulum stress response, which was reported as an oncogene in non-small cell lung cancer (NSCLC) tumorigenesis and development. However, the regulatory mechanism of XBP1 expression in NSCLC progression was less reported. N6-methyladenosine (m⁶A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression. This study aimed to investigate the regulatory role of the m⁶A modification in XBP1 expression in NSCLC. We identified XBP1 as a downstream target of ALKBH5-mediated m⁶A modification in A549 and PC9 cells. Knockdown of ALKBH5 increased the m⁶A modification and the stability of XBP1 mRNA, while overexpression of ALKBH5 had the opposite effect. Furthermore, IGF2BP3 was confirmed to be a reader of XBP1 m⁶A methylation and to enhance the stability of XBP1 mRNA. Additionally, IGF2BP3 knockdown significantly reversed the increase in XBP1 stability mediated by ALKBH5 depletion. In vivo and in vitro experiments demonstrated that ALKBH5/IGF2BP3 promotes the proliferation, migration, and invasion of NSCLC cells by upregulating XBP1 expression. In addition, we also showed that XBP1 promoted NSCLC cell proliferation, migration, and invasion by activating IL-6-JAK-STAT3 signaling. Our research suggested that ALKBH5-mediated m⁶A modification of XBP1 facilitates NSCLC progression through the IL-6-JAK-STAT3 pathway.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470480","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}