Neoplasma最新文献

{"title":"ΔNp63 is regulated by insulin/IGF-1 signaling in normal basal/progenitor mammary cells and in luminal-type breast cancer cells.","authors":"Michaela Stenckova, Yajing Liu, Marta Nekulova, Jitka Holcakova, Zuzana Pokorna, Rudolf Nenutil, Alastair M Thompson, Borivoj Vojtesek, Philip John Coates","doi":"10.4149/neo_2023_230719N376","DOIUrl":"10.4149/neo_2023_230719N376","url":null,"abstract":"<p><p>Breast cancers are a heterogeneous group of tumors classified according to their histological growth patterns and receptor expression characteristics. Intratumor heterogeneity also exists, with subpopulations of cells with different phenotypes found in individual cancers, including cells with stem or progenitor cell properties. At least two types of breast cancer stem cells (CSCs) exist, the epithelial and the basal/mesenchymal subtypes, although how these phenotypes are controlled is unknown. ΔNp63 is a basal cell marker and regulator of stem/progenitor cell activities in the normal mammary gland and is expressed in the basal-like CSC subpopulation in some estrogen receptor-positive (ER+) and/or human epidermal growth factor receptor 2-positive (HER2+) breast adenocarcinomas. Whilst p63 is known to directly impart CSC properties in luminal breast cancer cells, how p63 is regulated and induced in these cells is unknown. We initially confirmed the existence of a small subpopulation of ΔNp63+ cells in lymph node metastases of ER+ human ductal adenocarcinomas, indicating together with previous reports that ΔNp63+ tumor cells are present in approximately 40% of these metastases. Notably, ΔNp63+ cells show a preferential location at the edge of tumor areas, suggesting possible regulation of ΔNp63 by the tumor microenvironment. Subsequently, we showed that the high levels of ΔNp63 in basal non-transformed MCF-10A mammary epithelial cells rely on insulin in their culture medium, whilst ΔNp63 levels are increased in MCF-7 ER+ luminal-type breast cancer cells treated with insulin or insulin-like growth factor 1 (IGF-1). Mechanistically, small molecule inhibitors and siRNA gene knockdown demonstrated that induction of ΔNp63 by IGF-1 requires PI3K, ERK1/2, and p38 MAPK activation, and acts through FOXO transcriptional inactivation. We also show that metformin inhibits ΔNp63 induction. These data reveal an IGF-mediated mechanism to control basal-type breast CSCs, with therapeutic implications to modify intratumor breast cancer cell heterogeneity and plasticity.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 5","pages":"621-632"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WITHDRAWN: Expression of Tmem41b and MMP13 associated with poor outcome in osteosarcomas.","authors":"Guo-Hua Li,&nbsp;Xiao Liu,&nbsp;Lin-Jie Feng,&nbsp;Liu Zhang","doi":"10.4149/neo_2021_201209N1329","DOIUrl":"https://doi.org/10.4149/neo_2021_201209N1329","url":null,"abstract":"<p><p>Ahead of Print article withdrawn by Publisher. The Publisher apologizes for any inconvenience this may cause.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10078025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel-based miR-192 delivery inhibits the development of hepatocellular carcinoma by suppressing the GSK3β/Wnt/β-catenin pathway.","authors":"Qing Yang,&nbsp;Xiaojv Zhuge,&nbsp;Weili Lin,&nbsp;Weilai Yu,&nbsp;Yu Zhu,&nbsp;Changsheng Shi,&nbsp;Zhengchao Shi","doi":"10.4149/neo_2023_230317N150","DOIUrl":"https://doi.org/10.4149/neo_2023_230317N150","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by high invasiveness, metastasis, and poor prognosis, which lacks effective treatments. Although the role of miR-192 in HCC development has been recognized, the underlying molecular mechanism is still poorly understood. This study aimed to explore the impact of mir-192 on HCC and its potential as a therapeutic strategy. Wound healing assay, Transwell assay, CCK-8 assay, and flow cytometry were performed to detect the impact of miR-192 on HCC cell metastasis, invasion, proliferation, and apoptosis, respectively. q-PCR and western blot were applied to measure the relative mRNA and protein expression of the GSK3β/Wnt/β-catenin pathway in miR-192-overexpressing cell lines. Immunofluorescence was carried out to detect the nuclear translocation of β-catenin. starBase website and dual luciferase reporter assay were used to verify the interaction between miR-192 and the target gene WNT10B 3'-untranslated region (3'-UTR) of the Wnt pathway. In addition, we developed algin/polyethyleneimine@miR-192 (AG/PEI@miR-192) nanohydrogel for in vivo delivery of miR-192-agomir. The results revealed that overexpressed miR-192 reduced the expression of HCC cell surface markers CD90, EpCAM, and CD133. Moreover, miR-192 overexpression inhibited HCC cell metastasis, invasion, and proliferation, promoted cell apoptosis, and reduced GSK3β/Wnt/β-catenin pathway expression. Additionally, AG/PEI@miR-192 exhibited good drug release and tumor inhibition. In conclusion, our study suggested that miR-192 inhibits HCC development by suppressing the GSK3β/Wnt/β-catenin pathway and proposed a promising hydrogel-based miR-192 delivery approach to hinder tumor growth.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"555-565"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA-329-3p suppresses proliferation and metastasis of endometrial carcinoma through downregulating E2F1.","authors":"Ruicong Wang,&nbsp;Chen Zhang,&nbsp;Wanting Guan,&nbsp;Qing Yang","doi":"10.4149/neo_2023_230410N196","DOIUrl":"https://doi.org/10.4149/neo_2023_230410N196","url":null,"abstract":"<p><p>Existing evidences have revealed the crucial roles of E2 promoter binding factor-1 (E2F1) during the tumorigenesis and progression process of multiple human tumors. However, the expression patterns, biological functions, as well as the underlying molecular mechanism of E2F1 in endometrial carcinoma yet remain largely unclear. The expression patterns and clinical prognostic value of E2F1 in endometrial carcinoma were evaluated using bioinformatics methods. Protein and mRNA, miRNA expression levels in tissues and cells were measured using immunohistochemistry, western blotting, and qRT-PCR assays. Cell viability and cell cycle distribution were examined using CCK-8 assay and flow cytometry, respectively. Scratch healing assay and Transwell assay were applied to measure cell migration and invasion ability. Bioinformatic analysis and luciferase reporter assays were conducted to confirm the targeting relationship between E2F1 and miR-329-3p. Moreover, a series of in vitro and in vivo functional experiments were employed to evaluate the effect of the miR-329-3p/E2F1 axis on cell growth and metastasis. Clinically, E2F1 was aberrantly expressed in endometrial carcinoma tissues and was correlated with advanced FIGO stage, histological type, p53 mutation, poor survival, and degree of tumor cell differentiation. ROC curves analysis also reveals that E2F1 has a high AUC value (up to 0.952, 95% CI: 0.915-0.988), indicating the promising diagnostic value of E2F1 level in endometrial carcinoma. In addition, in vitro gain and loss-of-functional experiments verified that high E2F1 can promote cell proliferation, cell cycle, migration, invasion, and EMT process. In-depth mechanism studies revealed that E2F1 was a downstream target gene of miR-329-3p, and miR-329-3p overexpression could effectively abrogate its promotion of cell malignant biological behavior. Collectively, our findings suggested that the miR-329-3p/E2F1 axis plays a crucial role in the progression of endometrial carcinoma, indicating that E2F1 can be considered a promising diagnostic and prognostic biomarker for endometrial carcinoma patients.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"566-579"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA HIF1A-AS2 mediates imatinib resistance by regulating autophagy in gastrointestinal stromal tumor cells.","authors":"Jingyi Yan,&nbsp;Xiaolei Chen,&nbsp;Ji Lin,&nbsp;Xuecheng Sun,&nbsp;Wei Chen","doi":"10.4149/neo_2023_230523N272","DOIUrl":"10.4149/neo_2023_230523N272","url":null,"abstract":"<p><p>The aim of this study was to explore the role and mechanism of long non-coding RNA (lncRNA) HIF1A antisense RNA 2 (HIF1A-AS2) in regulating imatinib (IM) resistance in gastrointestinal stromal tumor (GIST) cells under hypoxia. The expression of HIF1A-AS2 was silenced by siRNA in GIST cells. Cytotoxicity, apoptosis, and autophagy were evaluated under normoxic and hypoxic conditions. The expression levels of HIF1A-AS2, HIF1A, apoptosis-associated genes, and autophagy-associated genes were determined by qRT-PCR analysis and western blot. We found that lncRNA HIF1A-AS2 was highly expressed in GIST tissues and cells. Knockdown of HIF1A-AS2 increased the sensitivity of GIST cells to IM and increased apoptosis. Moreover, a hypoxic environment decreased the sensitivity of GIST cells to IM, and the knockdown of HIF1A-AS2 reversed this effect. Mechanistically, the knockdown of HIF1A-AS2 inhibited IM-mediated autophagy. Finally, HIF1A was found to positively regulate HIF1A-AS2 under hypoxic conditions. Collectively, these data demonstrate that hypoxia-induced HIF1A-AS2 promotes IM resistance in GIST cells by regulating autophagy.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"526-533"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41149988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of physical exercise and dairy probiotics (Lactobacillus casei) on gut microbiome in childhood cancer survivors.","authors":"Viktor Bielik,&nbsp;Ivan Hric,&nbsp;Sabína Šmahová,&nbsp;Miriam Tkačiková,&nbsp;Veronika Hlaváčová,&nbsp;Libuša Nechalová,&nbsp;Simona Ugrayová,&nbsp;Alexandra Kolenová","doi":"10.4149/neo_2023_230526N287","DOIUrl":"https://doi.org/10.4149/neo_2023_230526N287","url":null,"abstract":"<p><p>Gut microbial dysbiosis persists months after intensive cancer treatment in children and adolescents. This prospective study compared the intestinal microbiome of children 1-3 years after completion of Berlin-Frankfurt-Münster protocol (BFM)-based pediatric ALL (PALL) treatment and healthy controls. To induce a favorable shift in the bacterial composition of the intestines in PALL with gut microbiome disruptions, 8 weeks of physical activity and probiotic consumption were used. Blood analyses and 16S rRNA sequencing for the gut microbiome were performed on 16 pediatric cases and 16 healthy controls. Significant differences in bacterial diversity were found between pre- and post-intervention, respectively (Shannon index, 3.22±0.45 vs. 3.47±0.24, p=0.04; Simpson index, 0.10±0.05 vs. 0.06±0.02, p=0.02; and Chao1 index, 693.88±238.58 vs. 794.23±116.34, p=0.04). Furthermore, the increase in the relative abundance of Lactobacillus casei (5.04E-03±1.62E-02 vs. 2.92E-02±5.03E-02, p=0.04) and the increase in some strains of Veillonella, a bacterial genus recently linked to improved physical fitness, were identified. Promisingly, the exercise program combined with dairy probiotics increased bacterial richness and diversity.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"588-596"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Camrelizumab combined with apatinib in the treatment of patients with hepatocellular carcinoma: a real-world assessment.","authors":"Dongbo Chen,&nbsp;Xiangxun Chen,&nbsp;Lei Xu,&nbsp;Yichun Wang,&nbsp;Liyang Zhu,&nbsp;Mei Kang","doi":"10.4149/neo_2023_230413N206","DOIUrl":"https://doi.org/10.4149/neo_2023_230413N206","url":null,"abstract":"<p><p>Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"580-587"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the complexity: A comprehensive analysis of the PP2A in cancer and its potential for novel targeted therapies.","authors":"Danica Ivovič,&nbsp;Pavlína Kabelíková,&nbsp;Dana Jurkovičová","doi":"10.4149/neo_2023_230806N411","DOIUrl":"10.4149/neo_2023_230806N411","url":null,"abstract":"<p><p>Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase considered a potent tumor suppressor that critically regulates diverse cellular processes, including cell cycle progression, apoptosis, or DNA repair. PP2A is typically downregulated in cancers but mechanisms for its inactivation in human cancers are poorly understood. PP2A represents a family of more than 60 phosphatases. According to cellular context, each heterotrimeric PP2A holoenzyme exerts a unique role in cancer, and PP2A isoforms can act either as tumor suppressors or as promoters. Due to wide structural diversity, PP2A has been considered undruggable. However, increasing knowledge predisposes PP2A diversity to therapeutical targeting for the treatment of a broad range of cancer pathologies, including drug resistance or cloaking immune surveillance. In this review, we discuss the regulatory role of PP2A in cancer, its regulation by microRNA and hypoxia, its contribution to therapy resistance development, and the therapeutic potential of direct and indirect targeting, or combinatory administration with other anti-cancer drugs to improve cancer treatment outcomes.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"485-499"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migration-inducing gene-7 promotes glioma cell proliferation and invasiveness via activating the MAPK signaling pathway.","authors":"Zhigang Pan,&nbsp;Chunhui Chen,&nbsp;Xinyue Huang,&nbsp;Yu Xiong,&nbsp;Xiaodong Kang,&nbsp;Jianfeng Zhou,&nbsp;Xiumei Guo,&nbsp;Shuni Zheng,&nbsp;Cui'e Wang,&nbsp;Feng Zheng,&nbsp;Weipeng Hu","doi":"10.4149/neo_2023_230307N121","DOIUrl":"https://doi.org/10.4149/neo_2023_230307N121","url":null,"abstract":"<p><p>Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"534-544"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel model of triple-negative breast cancer produces viable circulating tumor cells and rapid lung metastasis for functional testing in vivo.","authors":"Jana Plava,&nbsp;Lenka Trnkova,&nbsp;Peter Makovicky,&nbsp;Michal Mego,&nbsp;Svetlana Miklikova,&nbsp;Lucia Kucerova","doi":"10.4149/neo_2023_230404N185","DOIUrl":"https://doi.org/10.4149/neo_2023_230404N185","url":null,"abstract":"<p><p>Breast cancer metastases are the main reason for women´s highest cancer mortality. Even though tumor cell dissemination via circulating tumor cells (CTC) released from the primary site is a very ineffective process, distant metastases appear in 46% of triple-negative breast cancer (TNBC) patients corresponding to the disease aggressiveness. Laboratory models for functional testing which mimic the spread of metastatic cells are needed for efficient investigation of the underlying mechanisms and therapeutic intervention. Here, we describe novel isogenic variants LMC3 and CTC3 of human TNBC cell line MDA-MB-231 that were derived by repeated injection of tumor cells into the tail vein of immunodeficient mice and subsequent selection of metastatic cells from lung metastases. These variants have increased migration potential, altered expression profiles, and elevated tumorigenic potential. Moreover, cell line CTC3 readily produces metastases in the lungs and bone marrow and detectable viable circulating tumor cells in the blood. This model enables rapid and cost-efficient strategies for biomarker exploration and novel intervention approaches to limit the CTC presence in the blood and hence tumor dissemination.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"514-525"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41122091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}