Stephanie J Wang, Wesley Kidder, Nancy M Joseph, Bryan Khuong Le, Sheila Lindsay, Farhana Moon, Eric K Nakakura, Li Zhang, Emily K Bergsland
{"title":"Factors associated with grade progression in pancreatic neuroendocrine tumors.","authors":"Stephanie J Wang, Wesley Kidder, Nancy M Joseph, Bryan Khuong Le, Sheila Lindsay, Farhana Moon, Eric K Nakakura, Li Zhang, Emily K Bergsland","doi":"10.1530/ERC-24-0203","DOIUrl":"10.1530/ERC-24-0203","url":null,"abstract":"<p><p>Grade progression of well-differentiated pancreatic neuroendocrine tumors (panNETs) can occur over time, with G1/2 to G3 being the most clinically relevant form. Here, we conducted a retrospective cohort study of 66 patients with initially G1/2 panNET (median initial Ki67, 4.6%). Patients were followed up for a median 6.8 years and had a median of two metachronous tumor biopsies over their disease course. 34.8% of patients underwent any form of grade progression, including G1 to G2/3 and G2 to G3, while 24.2% demonstrated G1/2 to G3 grade progression. Over a median 2.3 years, G1/2 to G3 grade progressors experienced a median Ki67 change of +27.0% (range, +6.4 to +48.7%). Subsequent biopsies showing progression to G3 had a median Ki67 value of 31.0% (range, 21.0-60.0%) and were more often performed following suspicious clinical behavior (75.0%) rather than routinely at the time of scheduled procedure/surgery (25.0%). Similar to prior studies, G1/2 to G3 grade progressors had worse overall survival from the time of metastatic disease (median, 4.8 years vs not reached for stably G1/2 disease; P = 0.002). Heavier pretreatment and heterogeneity or lack of uptake on somatostatin receptor imaging was independently associated with progression to G3. In the largest study of metachronous panNET biopsies to date, our findings show that baseline biopsies suggesting G1/2 disease may not accurately reflect future disease status, highlighting the possible limitations of using archived tissue to stratify patients into trials and/or choose future therapy. Additional work is needed to better understand the impact of prior therapies on grade progression and how to identify which lesions to best follow up for repeat biopsy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pauline Bourdeleau, Johanna Pokossy-Epée, Olivia Hentic, Matthieu Tihy, Zaima Afzal Awan, Anne Couvelard, Maxime Ronot, Vinciane Rebours, Philippe Ruszniewski, Jérôme Cros, Louis de Mestier
{"title":"Temporal increase in Ki-67 index in patients with pancreatic neuroendocrine tumours.","authors":"Pauline Bourdeleau, Johanna Pokossy-Epée, Olivia Hentic, Matthieu Tihy, Zaima Afzal Awan, Anne Couvelard, Maxime Ronot, Vinciane Rebours, Philippe Ruszniewski, Jérôme Cros, Louis de Mestier","doi":"10.1530/ERC-24-0321","DOIUrl":"10.1530/ERC-24-0321","url":null,"abstract":"<p><p>Pancreatic neuroendocrine tumours (PanNETs) have intra-tumour heterogeneity, notably regarding the Ki-67 index, which is a major prognostic factor. The temporal evolution of PanNET biology is poorly known. We aimed to study the prognostic impact of the temporal evolution of Ki-67 and other molecular markers (MEN1, ATRX/DAXX and PDX1/ARX) in PanNETs. We retrospectively studied 109 patients with sporadic PanNETs and serial tumour samples (n = 286), in which we measured the Ki-67 index and the expression of the other markers. Variables associated with shorter overall survival (OS) and Ki-67 increase over time were explored using multivariable analyses. The median time between the initial and last samples was 49.4 months, with a median variation in Ki-67 of +4% (interquartile range (IQR): -1 to +15%; P < 0.001) and +0.5%/year (IQR: -0.2 to +3.3%). Tumour grade increased in 36% of cases. At multivariable analysis, an increase in Ki-67 ≥ 2%/year was associated with shorter OS (HR 1.96, 95% CI [1.02-3.73], P = 0.041). This variation was more common in patients who received alkylating agents (OR 4.47, 95% CI [1.48-15.38], P = 0.011) and was less common in those who achieved tumour control with somatostatin analogues (OR 0.27, 95% CI [0.08-0.82], P = 0.027). MEN1 and ATRX/DAXX expressions were stable over time, while the proportion of alpha-like signatures (PDX1-/ARX+) decreased (P = 0.016); none was associated with Ki-67 nor influenced prognosis. Overall, an increase in PanNET grade and Ki-67 index is frequent over time, indicates a poorer prognosis and is promoted by alkylating agents. Rebiopsy during PanNET evolution seems relevant to adjust prognosis evaluation and therapeutic strategy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miguel Chenlo, Ignacio Bernabeu, Márta Korbonits, Clara V Alvarez
{"title":"RET signalling in the pituitary: a double-edged sword for differentiation, apoptosis and therapeutic strategies in acromegaly.","authors":"Miguel Chenlo, Ignacio Bernabeu, Márta Korbonits, Clara V Alvarez","doi":"10.1530/ERC-24-0156","DOIUrl":"10.1530/ERC-24-0156","url":null,"abstract":"<p><p>The discovery of RET mutations in multiple endocrine neoplasia type 2A (MEN2A) in 1993 ignited a revolution in our understanding of this versatile receptor. Since then, the influence of RET has expanded to encompass diverse organs, including the pituitary gland. This review explores the multifaceted role of RET in somatotrophs, focusing on two opposing pathways: proliferation versus differentiation and apoptosis. The binding of glial-derived neurotrophic factor (GDNF) to RET promotes pituitary cell survival and inhibits PIT1-dependent differentiation, while low levels of GDNF trigger differentiation via PIT1. Excessive PIT1, on the other hand, will lead to apoptosis through caspase-3 activation involving the adaptor protein AIP and CDKN2A-ARF/p53. Pathogenic mutations in AIP can disrupt this apoptotic pathway, contributing to somatotrophinoma or prolactinoma development. In this concise review, we highlight the potential of CDKN2A-ARF expression as a prognostic marker for therapy response and discuss the promise of novel RET tyrosine kinase inhibitors for aggressive somatotrophinomas.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xianhui Ruan, Mei Tao, Yuanxing Dong, Linfei Hu, Guangwei Xu, Chuanxiang Hu, Yue Huang, Yuqi Wang, Jialong Yu, Wei Luo, Ming Gao, Min Zhao, Xiangqian Zheng
{"title":"Persistent pre-exhausted CD8+ T cells shape the tumor immune microenvironment in anaplastic thyroid cancer.","authors":"Xianhui Ruan, Mei Tao, Yuanxing Dong, Linfei Hu, Guangwei Xu, Chuanxiang Hu, Yue Huang, Yuqi Wang, Jialong Yu, Wei Luo, Ming Gao, Min Zhao, Xiangqian Zheng","doi":"10.1530/ERC-24-0169","DOIUrl":"10.1530/ERC-24-0169","url":null,"abstract":"<p><strong>Abstract: </strong>Anaplastic thyroid cancer (ATC) is an aggressive form of cancer with poor prognosis, heavily influenced by its tumor immune microenvironment (TIME). Understanding the cellular and gene expression dynamics within the TIME is crucial for developing targeted therapies. This study analyzes the immune microenvironment of ATC and papillary thyroid cancer (PTC) using single-cell RNA sequencing (scRNA-seq). We performed a comprehensive scRNA-seq analysis on ATC and PTC samples, incorporating cell type annotation, marker gene identification and clustering based on gene expression. A specific focus was on the prevalence and biomarkers of pre-exhausted CD8+ T cells in ATC, utilizing the single-cell tumor immune atlas for immune cell characterization. The scRNA-seq analysis identified distinct immune cell populations and differentially expressed genes in ATC and PTC samples. Notably, pre-exhausted CD8+ T cells were found to be prevalent in ATC datasets. Additional immunofluorescence staining and coculture experiments with the ATC cell line identified GNLY, a member of the saposin-like protein family, as a potential biomarker for pre-exhausted CD8+ T cells in ATC. This study provides valuable insights into the immune landscape of ATC, emphasizing the prevalence of pre-exhausted CD8+ T cells and identifying GNLY as a potential biomarker. Understanding the TIME composition and the role of specific immune cells in cancer progression can inform the development of targeted immunotherapies for ATC. Future research should explore the functional implications of GNLY and other identified biomarkers in modulating the immune response in thyroid cancer.</p><p><strong>Highlights: </strong>A computational pipeline was constructed to identify ATC-specific immune cell populations and differentially expressed genes via multiple independent ATC and PTC single-cell transcriptomes.A total of 221 uniquely differentially expressed genes associated with the adaptive immune response across two ATC datasets were identified.Markedly prevalent pre-exhausted CD8+ T cells in ATC datasets compared with PTC datasets were identified.One hundred fifteen potential biomarker genes of pre-exhausted CD8+ T cells were identified, with GNLY experimentally validated as the top candidate.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elias Karam, Marcus Hollenbach, Christian Heise, Einas Abou Ali, Aiste Gulla, Francesco Auriemma, Benoît Terris, François R Souche, Charles de Ponthaud, Thomas Hank, Fabrice Caillol, Rami Rhaiem, Alain Sauvanet, Bertrand Napoléon, Sara Regner, Sébastien Gaujoux
{"title":"Ampullary composite gangliocytoma/neuroma and neuroendocrine tumor management.","authors":"Elias Karam, Marcus Hollenbach, Christian Heise, Einas Abou Ali, Aiste Gulla, Francesco Auriemma, Benoît Terris, François R Souche, Charles de Ponthaud, Thomas Hank, Fabrice Caillol, Rami Rhaiem, Alain Sauvanet, Bertrand Napoléon, Sara Regner, Sébastien Gaujoux","doi":"10.1530/ERC-24-0238","DOIUrl":"10.1530/ERC-24-0238","url":null,"abstract":"<p><p>Ampullary composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET), previously called ampullary gangliocytic paragangliomas, is a rare entity, with only few reported cases in the literature. This is a multicentric retrospective cohort study of patients treated with endoscopy or surgery for ampullary CoGNET. A literature review of ampullary CoGNET was also performed. Fifteen patients were included, mostly female (n = 10) with a median age of 50 years. Patients were asymptomatic in seven cases. Four patients were treated with pancreatoduodenectomy, four with transduodenal ampullectomy, and eight with endoscopic papillectomy. Clavien-Dindo III-IV complications occurred in 2 of the 8 surgical cases, but no fatal adverse events were registered. There was only one moderate endoscopic adverse event. The median length of stay was 9 days. The median tumor size was 20 mm, the R0 resection rate was 93.8%, and two patients had nodal involvement. After a median follow-up of 29 months, there was no local or distant recurrence nor death from disease. The literature review confirmed the clinical presentation and excellent outcomes of ampullary CoGNET management, especially regarding survival, even for patients with nodal or distant metastases. Overall, ampullary CoGNET are rare tumors with excellent prognosis, even with incomplete resection or nodal involvement. Treatment should be as minimally invasive as possible, and a long-term follow-up is needed.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dana Hamadi, John J Schmitz, Chris N Gu, Hillary W Garner, Anil N Kurup, Marius N Stan
{"title":"Needle tract seeding of thyroid cancer after biopsy of distant metastasis: a retrospective cohort.","authors":"Dana Hamadi, John J Schmitz, Chris N Gu, Hillary W Garner, Anil N Kurup, Marius N Stan","doi":"10.1530/ERC-24-0263","DOIUrl":"10.1530/ERC-24-0263","url":null,"abstract":"<p><p>Imaging-guided percutaneous core needle biopsy is currently the most common technique for the investigation of potentially malignant bone lesions. It allows precise needle placement and better visual guidance, leading to improved diagnostic accuracy. Needle tract seeding (NTS) is a rare complication of biopsies in general, and its true incidence remains unknown. This study aimed to assess the risk of NTS in patients with thyroid cancer who underwent bone biopsy. For our cohort, we extracted data from the electronic medical record at the Mayo Clinic in Rochester (Minnesota, USA). Inclusion criteria included patients with a history of thyroid cancer who underwent biopsy for bone metastasis between 1/1/2014 and 10/1/2023. We identified a cohort of 20 patients that fit our inclusion criteria. Of these 20 patients, 2 patients developed NTS after CT-guided bone biopsy. Cases of seeding had a larger tumor size, a more aggressive histopathological presentation, a significantly shorter duration between cancer diagnosis and bone metastasis, and underwent more tumor manipulation procedures, such as biopsy and radiofrequency ablation, in contrast to those without seeding. In conclusion, our study identified NTS to have an incidence of 10% after biopsies of bone metastasis related to thyroid carcinoma. These are likely the result of an interplay of risk factors, including tumor biology, penetrated tissues and procedural technical details. Further studies with larger sample sizes are needed to confirm our findings and identify strategies to mitigate NTS.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Systems-level liquid biopsy in advanced prostate cancer.","authors":"Jacqueline Lyman, Scott M Dehm","doi":"10.1530/ERC-24-0274","DOIUrl":"10.1530/ERC-24-0274","url":null,"abstract":"<p><p>Treatment for castration-resistant prostate cancer (CRPC) primarily involves suppression of androgen receptor (AR) activity using androgen receptor signaling inhibitors (ARSIs). While ARSIs have extended patient survival, resistance inevitably develops. Mechanisms of resistance include genomic aberrations at the AR locus that reactivate AR signaling or lineage plasticity that drives emergence of AR-independent phenotypes. Given the diverse mechanisms of ARSI resistance in CRPC, there is a need for more effective monitoring strategies that detect signs of resistance to inform prognosis and guide use of alternative therapies. Liquid biopsy is a blood test that has emerged as a powerful, minimally invasive tool for investigating advanced cancer. In CRPC, liquid biopsy has been shown to reflect genomic and transcriptomic features in tumor tissue and has been utilized to detect an array of resistance signatures. Liquid biopsy is uninhibited by spatial restrictions and allows for longitudinal monitoring of disease progression. However, current clinical liquid biopsy tests provide limited actionable information. This review highlights recent advancements to the understanding of mechanisms driving treatment resistance in CRPC through research-grade liquid biopsy assays. We explore novel methods of disease characterization developed using liquid biopsy and emphasize the clinical potential of a multi-omics molecular profiling approach to comprehensively detect emerging therapeutic resistance. Routine assessment of therapy resistance using a liquid biopsy assay has the potential to enhance prognostication and improve outcomes of men with CRPC.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bone metastasis in endocrine-related cancer: unravelling invasion and destruction.","authors":"Huong Q Duong, Georgia Kafer, Michelle Maugham-Macan","doi":"10.1530/ERC-24-0294","DOIUrl":"10.1530/ERC-24-0294","url":null,"abstract":"<p><p>Bone is a common and debilitating site for metastatic cancer cell expansion. Skeletal metastasis is a multistage process, with primary stages of circulating tumour cells, progressing to a dormant state in vasculature and bone marrow niches, followed by tumourigenic reactivation, proliferation and finally bone destruction. The frequency of bone metastasis is reconciled in Paget's 'seed and soil' hypothesis, where a conducive microenvironment (bone niche) is essential for cancer cell colonisation. Cancer cells can mimic bone cells (osteomimicry) and interact with the bone marrow's vascular architecture, utilising pathways akin to haematopoietic stem cell expansion. Current research suggests that each phase of bone metastasis is associated with specific gene expression and protein abundance patterns. For example, E-selectin, CXCR-4 and CXCL-12 are crucial for cancer cell homing, dormancy and colonisation of bone tissue. In contrast, different primary cancers appear to have unique staging profiles. In prostate cancer, dormancy is modulated by the CXCR-4/CXCL-12, ANXA2/CXCL12 and GAS6 pathways, while in breast cancer, dormancy involves ERK1/2, p38, MSK1, LIF, BMP-7, TGF-β1/2 and bone resorption factors. Conversely, osteoblastic metastasis in both breast and prostate cancers is characterised by ET-1, Dkk1 suppression and the release of IL-6, MCP-1, VEGF, FGF and IGF, while osteolytic metastasis primarily depends on PTHrP, RANKL, OPG, TGF-β, IGF, TNF-α, IL-1 and IL-7. Understanding the complex molecular mechanisms facilitating cancer cell colonisation and expansion in bone tissues is essential for developing effective treatments to prevent bone metastases. In this review, we discuss current theories linking bone remodelling with bone.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shengyuan Yu, Quanxi Duan, Changcun Niu, Chengzhi Mu
{"title":"Activation of the HIF1α/TIMP1/MT6-MMP pathway is associated with invasion in pituitary null cell adenomas.","authors":"Shengyuan Yu, Quanxi Duan, Changcun Niu, Chengzhi Mu","doi":"10.1530/ERC-24-0146","DOIUrl":"10.1530/ERC-24-0146","url":null,"abstract":"<p><p>Non-functioning pituitary adenomas (NFPAs) are a highly heterogeneous group and often show invasion, but few studies have explored the invasion mechanism and biomarkers for specific subtypes. This study was designed to describe the role of HIF1α and its downstream genes in specific subtypes of NFPAs. Specimens were classified into two subtypes of NFPAs: 46 null cell adenomas (28 invasive and 18 noninvasive) and 46 oncocytomas (11 invasive and 35 noninvasive). HIF1α, TIMP1, MT6-MMP, ECAD and NCAD were detected by qRT-PCR, western blot or immunohistochemistry in tumor tissue. The transwell assay was performed to measure the effects of HIF1α on tumor cell invasion in GH3 and GT1-1 cells. TIMP1, MT6-MMP, ECAD and NCAD were detected by western blot in HIF1α overexpressed GT1-1 cells. HIF1α mRNA and protein level was significantly upregulated in invasive pituitary null cell adenomas but not in invasive pituitary oncocytoma. The TIMP1 mRNA and protein level was significantly downregulated and MT6-MMP mRNA and protein level was significantly upregulated in invasive pituitary null cell adenomas. Meanwhile, there were no significant differences in epithelial-mesenchymal transition (EMT) markers, ECAD and NCAD, between invasive and noninvasive pituitary null cell adenomas. The overexpression of HIF1α promoted the invasive capability of pituitary adenoma cells in vitro. Regarding the molecular mechanism, HIF1α overexpression could downregulate TIMP1 and upregulate MT6-MMP expression levels but did not affect EMT markers' expression. Our results suggested that HIF1α might contribute to the invasion of pituitary null cell adenomas through activating HIF1α/TIMP1/MT6-MMP pathway but not EMT.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}