Neoplasia最新文献

{"title":"Post-transcriptional control of HIF-1α by MBNL1 restrains hypoxia-driven stemness in GBM","authors":"Blair P. Rendina ,&nbsp;Fahim Ahmad ,&nbsp;Luka Akerman ,&nbsp;Ian Mills ,&nbsp;Nina C. Lee ,&nbsp;Chixiang Chen ,&nbsp;Haoyu Ren ,&nbsp;Xiaoxuan Fan ,&nbsp;Jeffrey A. Winkles ,&nbsp;Graeme F. Woodworth ,&nbsp;Gerald M. Wilson ,&nbsp;Eli E. Bar","doi":"10.1016/j.neo.2025.101262","DOIUrl":"10.1016/j.neo.2025.101262","url":null,"abstract":"<div><div>MBNL1 binds the HIF-1α 3′UTR to promote rapid mRNA decay, thereby limiting HIF-1 activity and hypoxia-induced stemness in glioblastoma. Using patient-derived glioma stem cells, we show that MBNL1 loss stabilizes HIF-1α mRNA and increases HIF-1α protein, HRE reporter activity, and target gene expression under hypoxia; MBNL1 knockout also prolongs target gene expression after reoxygenation, indicating enhanced hypoxia “memory.” MBNL1 depletion markedly elevates stemness markers (KLF4, SOX2, GLI1) and clonogenic growth, and re-expression of MBNL1 reverses these effects. These results identify a post-transcriptional MBNL1–HIF1α axis that controls hypoxia signaling and stemness, with implications for GBM therapy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101262"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145697766","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":"Polyploid cisplatin-resistant cancer cells have altered nuclear organization and epigenomic status","authors":"Anna LK Gonye ,&nbsp;Linda Orzolek ,&nbsp;Christopher Cherry ,&nbsp;Michael Patatanian ,&nbsp;Luke V Loftus ,&nbsp;Kevin Truskowski ,&nbsp;George Butler ,&nbsp;Kenneth J Pienta ,&nbsp;Sarah R Amend","doi":"10.1016/j.neo.2025.101268","DOIUrl":"10.1016/j.neo.2025.101268","url":null,"abstract":"<div><div>Chemotherapy resistance remains a critical barrier in cancer treatment, partly driven by polyploid cells that survive therapy and contribute to tumor recurrence. Here, we investigated epigenomic and transcriptional changes associated with cisplatin-surviving polyploid cells compared to parental cancer cells in prostate cancer (PC3) and triple-negative breast cancer (MDA-MB-231) cell lines. We observed persistent dysregulation of chromatin compaction and altered nuclear structure in polyploid cells following cisplatin treatment. Genome-wide chromatin accessibility profiling via ATAC-seq revealed significant remodeling, notably decreased promoter accessibility at proliferation-associated loci and increased accessibility of distal regulatory elements linked to inflammation and stress response. RNA-seq analyses demonstrated a coordinated transcriptional shift away from proliferative signatures toward inflammatory and survival pathways, including activation of NFκB, interferon response, and integrated stress response pathways. Importantly, we identified subsets of genes showing concordant changes in promoter accessibility and transcriptional activity, directly linking chromatin remodeling to transcriptional reprogramming. These integrated findings highlight the role of chromatin dynamics and epigenetic plasticity in chemotherapy resistance, demonstrating that widespread chromatin accessibility changes facilitate the transition to a stress-adapted, polyploid cell state. This study provides new insights into the molecular mechanisms supporting cancer cell persistence after chemotherapy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101268"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031359","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":"THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression","authors":"Shreya Budhiraja ,&nbsp;Umme H. Faisal ,&nbsp;Shivani Baisiwala ,&nbsp;Rafal Chojak ,&nbsp;Lara Koutah ,&nbsp;Noah B. Drewes ,&nbsp;Sia Cho ,&nbsp;Hasaan A Kazi ,&nbsp;Rebecca Chen ,&nbsp;Ella N Perrault ,&nbsp;Li Chen ,&nbsp;Cheol H. Park ,&nbsp;Maeve C. O’Shea ,&nbsp;Khizar Nandoliya ,&nbsp;Joseph T. Duffy ,&nbsp;Peiyu Lin ,&nbsp;Adam M Sonabend ,&nbsp;Crismita C. Dmello ,&nbsp;Atique U. Ahmed","doi":"10.1016/j.neo.2025.101271","DOIUrl":"10.1016/j.neo.2025.101271","url":null,"abstract":"<div><div>Glioblastoma (GBM), the most common and aggressive primary malignant brain tumor in adults, has a median survival of 14.6 months. To identify drivers of GBM pathogenesis, we conducted a CRISPR-knockout screen, which revealed THO Complex 1 (THOC1) as a key driver. Knocking down THOC1 significantly reduced GBM cell viability across patient-derived xenograft (PDX) lines, enhancing survival (p&lt;0.01) in primary PDX models. Conversely, overexpressing THOC1 in non-cancerous neural stem cells bolstered transformation capacity, decreasing survival and causing tumor engraftment <em>in vivo</em> (p&lt;0.01). Further investigation revealed THOC1′s interaction with SIN3A, a histone deacetylase complex. Histone deacetylation has been previously shown to prevent the buildup of R-loops, structures that form normally during transcription but can be lethal in excess. We found that THOC1-knockdown leads to elevated R-loop levels and reduced histone deacetylation levels. RNA-sequencing analysis revealed that THOC1’s role in R-loop prevention primarily affects telomeres, critical regions for cell replication. We further show that THOC1-knockdown results in significantly increased telomeric R-loop levels and shortened telomeres. Ultimately, this study suggests that targeting THOC1 is a promising therapeutic strategy to disrupt the delicate R-loop landscape and undermine GBM's replicative potential.</div></div><div><h3>STATEMENT OF SIGNIFICANCE</h3><div>Glioblastoma, the most aggressive malignant brain tumor in adults, relies on a delicate R-loop landscape to promote cell replication while avoiding DNA damage. Targeting THOC1 represents a promising therapeutic strategy to disrupt the delicate R-loop landscape and undermine GBM's replicative potential.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101271"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913716","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":"Corrigendum to “GBP1-CDK9-STAT3 signaling axis promotes osteosarcoma PD-L1 expression and immune escape” [Neoplasia 69 (2025) 101232]","authors":"Doudou Jing ,&nbsp;Binghong Chen ,&nbsp;Ruqi Liang ,&nbsp;Fei Li ,&nbsp;Bin Zhao ,&nbsp;Feifei Pu ,&nbsp;Wei Wu","doi":"10.1016/j.neo.2026.101273","DOIUrl":"10.1016/j.neo.2026.101273","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101273"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031301","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":"Visceral adiposity as a metabolic risk factor for bone tumors: Insights from the NHANES population-based study","authors":"Xianliang Wang ,&nbsp;Rengcheng Qian ,&nbsp;Zhenlang Lin ,&nbsp;Yiying Wang","doi":"10.1016/j.neo.2025.101265","DOIUrl":"10.1016/j.neo.2025.101265","url":null,"abstract":"<div><h3>Background</h3><div>Bone tumors are rare but highly aggressive malignancies associated with considerable mortality. Emerging evidence identifies obesity as a contributor to multiple malignancies, including those of osseous origin, primarily through mechanisms involving endocrine imbalance and chronic inflammation. Conventional obesity metrics, like body mass index (BMI), cannot reflect the full spectrum of obesity-related risks. In contrast, the age-adjusted visceral adiposity index (AVAI) offers a more holistic evaluation of obesity-associated hazards.</div></div><div><h3>Methods</h3><div>This cross-sectional analysis utilized National Health and Nutrition Examination Survey (NHANES) data collected between 2011 and 2018. After excluding participants younger than 18 years and those lacking complete information on bone tumors or AVAI, the final analytic cohort comprised 3,731 adults. The AVAI was calculated using BMI, waist circumference, age, high-density lipoprotein levels, and triglyceride levels. The presence of a bone tumor was ascertained through medical questionnaires. Logistic regression analyses were applied to evaluate the association between AVAI levels and the occurrence of bone neoplasms, after adjusting for potential confounders such as hypertension, diabetes, and other metabolic variables.</div></div><div><h3>Results</h3><div>The prevalence of bone tumors increased with higher AVAI quartiles, reaching 4.07 % in the highest quartile (Q4). Univariate logistic regression demonstrated a significant positive association between AVAI and bone tumors (OR = 1.19, 95 % CI: 1.02–1.31, <em>P</em> &lt; 0.0001). After accounting for all demographic, metabolic, and clinical covariates, higher AVAI quartiles remained strongly associated with elevated bone tumor risk, with adjusted odds ratios of 1.64 (Q2), 2.15 (Q3), and 2.81 (Q4) compared to the reference quartile (Q1).</div></div><div><h3>Conclusion</h3><div>The findings indicate a significant association between AVAI and the likelihood of bone tumor development, thus emphasizing the necessity of incorporating visceral adiposity into the assessment of skeletal neoplasm incidence. Future studies should focus on the underlying mechanisms and investigate potential interventions targeting obesity-related factors to mitigate the risk of bone tumors.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101265"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913719","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":"Corrigendum to “DAB2IP modulates primary cilia formation associated with renal tumorigenesis” [Neoplasia, Volume 23, Issue 1 (2021) 169–180]","authors":"Chun-Jung Lin,&nbsp;Andrew Dang,&nbsp;Elizabeth Hernandez,&nbsp;Jer-Tsong Hsieh","doi":"10.1016/j.neo.2026.101274","DOIUrl":"10.1016/j.neo.2026.101274","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101274"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034789","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":"LOXL2⁺ cancer-associated fibroblasts shape WNT signaling to drive chemoresistance and poor outcomes in colorectal cancer: Insights from multi-omics and epidemiological analyses","authors":"Chengyuan Xu ,&nbsp;Tengfei Li ,&nbsp;Lin Zhang ,&nbsp;Qin Zhang ,&nbsp;Shanshan Cai ,&nbsp;Qiangqiang Fu ,&nbsp;Siqi Zhang","doi":"10.1016/j.neo.2025.101267","DOIUrl":"10.1016/j.neo.2025.101267","url":null,"abstract":"<div><h3>Background</h3><div>Cancer-associated fibroblasts (CAFs) critically influence colorectal cancer (CRC) progression and therapy response, yet their epidemiological and molecular heterogeneity remains underexplored.</div></div><div><h3>Methods</h3><div>We integrated bulk, single-cell, and spatial transcriptomic datasets from multiple CRC cohorts, together with patient-derived tissues and functional assays, to delineate CAF subtypes and their clinical significance. Epidemiological analyses were performed across independent cohorts to evaluate the association between CAF markers and patient outcomes.</div></div><div><h3>Results</h3><div>A myofibroblastic CAF (myCAF) subset characterized by high LOXL2 expression was consistently enriched in advanced and chemoresistant CRC samples. Multi-omics correlation analyses revealed that LOXL2⁺ CAFs activated WNT signaling in adjacent tumor cells, promoting stemness and drug resistance. Across population-based cohorts, elevated LOXL2 expression was independently associated with poor overall and disease-free survival, as confirmed by multivariate Cox regression. Spatial transcriptomics and immunofluorescence demonstrated close physical interaction between LOXL2⁺ CAFs and WNT5A-positive cancer cells. Functional inhibition or genetic silencing of LOXL2 and wnt5a in CAFs restored chemosensitivity <em>in vitro</em> and suppressed tumor growth <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div>Our integrative epidemiological and experimental analyses identify LOXL2⁺ CAFs as a key stromal determinant of chemoresistance and poor prognosis in CRC. These findings highlight a clinically relevant stromal biomarker with potential for risk stratification and therapeutic targeting in colorectal cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101267"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913772","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":"Histone 3 lysine 56 acetylation (H3K56ac) regulates extrachromosomal DNA (ecDNA) hub maintenance","authors":"Li-Zhu Liao ,&nbsp;Chang-Jiun Wu ,&nbsp;Yu-An Chen ,&nbsp;Tzu-Chin Lin ,&nbsp;Po-Hung Lin ,&nbsp;Chia-Lin Wei ,&nbsp;Kou-Juey Wu","doi":"10.1016/j.neo.2025.101269","DOIUrl":"10.1016/j.neo.2025.101269","url":null,"abstract":"<div><div>Extrachromosomal DNAs (ecDNAs) play an important role in tumor progression. ecDNA hubs have been shown to be anchored by BRD4, a chromatin reader. However, the chromatin organization of ecDNA hub remains unknown. Here we show that histone 3 lysine 56 acetylation (H3K56ac) mark binds to BRD4 specifically. Knockdown of BRD4 decreased the ecDNA hub signals by the ecTag method. Knockdown of an epigenetic player (USP7), histone acetyltransferase (CBP), or histone chaperone (Asf1a) that regulates H3K56ac mark also decreased ecDNA hub signals and H3K56ac levels, supporting the role of H3K56ac in regulating ecDNA hub maintenance. Co-immunoprecipitation experiments showed the interactions of BRD4, USP7, Asf1a, and CBP. Analysis of ChIP-seq datasets showed that both H3K56ac and H3K27ac converged with BRD4 binding at the ecDNA-chromosome interaction sites and ecDNA itself. However, H3K56ac had a widespread enrichment with most BRD4-occupied sites compared with H3K27ac that occupied a limited subset of BRD4 peaks. These results present a framework of ecDNA hub chromatin organization that maintains ecDNA hub integrity, further providing therapeutic options that could be used to target ecDNA hubs.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101269"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913766","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":"Clonal architecture of FLT3-ITD and acquired 13q uniparental disomy define prognostic heterogeneity and therapeutic vulnerabilities in acute myeloid leukemia","authors":"Anli Lai ,&nbsp;Wenbing Liu ,&nbsp;Yihan Mei,&nbsp;Qimin Zhang,&nbsp;Junping Zhang,&nbsp;Kejing Tang,&nbsp;Qing Rao,&nbsp;Runxia Gu,&nbsp;Sizhou Feng,&nbsp;Ying Wang,&nbsp;Min Wang,&nbsp;Hui Wei,&nbsp;Yingchang Mi,&nbsp;Shaowei Qiu,&nbsp;Jianxiang Wang","doi":"10.1016/j.neo.2025.101264","DOIUrl":"10.1016/j.neo.2025.101264","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is characterized by the sequential accumulation of genetic mutations in hematopoietic stem/progenitor cells (HSPCs). The <em>FLT3</em>-ITD mutation, occurring in 20-30 % of AML cases, typically emerges as a late event. Despite its established association with adverse prognosis, significant outcome heterogeneity persists in <em>FLT3</em>-ITD AML. The clonal origin of <em>FLT3</em>-ITD may serve as a critical determinant of phenotypic and prognostic variability, though the underlying mechanisms remain poorly understood. This study enrolled 149 <em>FLT3</em>-ITD AML patients. Genomic and transcriptomic profiling defined four prognostic origin subtypes (<em>DNMT3A</em>/<em>NPM1</em>-mutation, <em>IDH</em>/<em>NPM1</em>-mutation, transcription factor [TF]-related lesion and other genetic lesion origin). Within the high risk <em>DNMT3A</em>/<em>NPM1</em>-origin subgroup, stratification by differentiation state showed hematopoietic stem cell arrest conferred an inferior event-free survival compared with arrest at the monocyte stage. Analysis of refractory/relapsed (R/R) cases revealed the prevalence of baseline 13q uniparental dismoy (UPD) in <em>DNMT3A</em>/<em>NPM1</em>-origin subgroup. All <em>DNMT3A</em>/<em>NPM1</em>-origin patients acquired 13q UPD at the R/R stage, arising from either expansion of pre-existing UPD subclones or de novo UPD acquisition under therapeutic pressure. Single-cell analysis further revealed aberrant activation of the DNA homologous recombination repair in <em>DNMT3A</em>/<em>NPM1</em>-origin patient blasts and triple-mutant mouse HSPCs. In conclusion, <em>FLT3</em>-ITD clonal origin demonstrated significant impact on the outcome of AML. Acquired 13q UPD drives clonal evolution and disease progression in the <em>DNMT3A</em>/<em>NPM1</em>-origin subgroup, highlighting its potential as a therapeutic target.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101264"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783511","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":"Differential chromatin accessibility response to retinoic acid in neuroblastoma with ATRX in-frame-deletions versus ATRX loss-of-function","authors":"Federica Lorenzi ,&nbsp;Matthew Shipley ,&nbsp;Luke Deane ,&nbsp;Robert Goldstone ,&nbsp;Vidur Tandon ,&nbsp;Barbara Martins da Costa ,&nbsp;Kevin Greenslade ,&nbsp;Karen Barker ,&nbsp;Fariba Nemati ,&nbsp;Angela Bellini ,&nbsp;Gudrun Schleiermacher ,&nbsp;Louis Chesler ,&nbsp;Francois Guillemot ,&nbsp;Sally L George","doi":"10.1016/j.neo.2025.101263","DOIUrl":"10.1016/j.neo.2025.101263","url":null,"abstract":"<div><div>Neuroblastoma is a childhood cancer, arising in the developing sympathetic nervous system. Differentiation therapy with 13-cis-retinoic acid (RA) is given to children with neuroblastoma to prevent relapse, however there is little understanding of which patients benefit. <em>ATRX</em> alterations are identified in 10 % of high-risk neuroblastomas and associated with poor outcomes. The commonest type of <em>ATRX</em> alterations in neuroblastoma are in-frame multi-exon deletions, followed by nonsense mutations predicted to result in loss-of-function (<em>ATRX</em> LoF).</div><div>We treated paired <em>ATRX</em> wild-type and LoF neuroblastoma cell-lines with RA: cells with <em>ATRX</em> LoF fail to upregulate direct RA target genes and show reduced chromatin accessibility differentiation and development related genes following RA treatment. Conversely, neuroblastoma models with in-frame deletions mount an appropriate epigenetic response to RA. Taken together this shows that the mechanism of differentiation in <em>ATRX</em>-altered neuroblastoma depends on the type of <em>ATRX</em> alteration, with implications relating to both oncogenesis and therapeutic response.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"72 ","pages":"Article 101263"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745268","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}