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Dual regulation of miR-375 and CREM genes in pancreatic beta cells 胰腺β细胞中miR-375和CREM基因的双重调控
IF 2.2 4区 医学
Islets Pub Date : 2022-04-04 DOI: 10.1080/19382014.2022.2060688
D. Keller, Isis G. Perez
{"title":"Dual regulation of miR-375 and CREM genes in pancreatic beta cells","authors":"D. Keller, Isis G. Perez","doi":"10.1080/19382014.2022.2060688","DOIUrl":"https://doi.org/10.1080/19382014.2022.2060688","url":null,"abstract":"ABSTRACT MicroRNA-375 (miR-375) is upregulated in the islets of some diabetics and is correlated with poor outcome. Previous work in our laboratory showed that cyclic adenosine monophosphate (cAMP) reduces miR-375 expression and could provide a way to restore normal miR-375 levels, however the transcription repression mechanism is unknown. Using a chromatin immunoprecipitation assay we show that cAMP response element modulator (CREM) binds to the miR-375 promoter 3-fold above background and we find that CREM represses transcription from the miR-375 promoter 1.8-fold. While investigating miR-375 target genes we discovered that several microRNA:mRNA target prediction algorithms listed human CREM as a target gene of miR-375. The predicted binding site is conserved in primates but not in other species. We found that indeed miR-375 binds to the predicted site on human CREM and represses translation of a green fluorescent protein reporter gene by 30%. These findings suggest a primate-specific double-negative feedback loop, a mechanism that would keep these important β-cell regulators in check. Graphical Abstract","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"139 - 148"},"PeriodicalIF":2.2,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45988547","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}
引用次数: 0
Modeling type 2 diabetes in rats by administering tacrolimus 他克莫司对大鼠2型糖尿病的影响
IF 2.2 4区 医学
Islets Pub Date : 2022-03-29 DOI: 10.1080/19382014.2022.2051991
J. C. Quintana-Pérez, F. García-Dolores, A. S. Valdez-Guerrero, Diana Alemán-González-Duhart, M. Arellano-Mendoza, S. Rojas Hernández, I. Olivares-Corichi, J. R. García Sánchez, J. T. Trujillo Ferrara, F. Tamay-Cach
{"title":"Modeling type 2 diabetes in rats by administering tacrolimus","authors":"J. C. Quintana-Pérez, F. García-Dolores, A. S. Valdez-Guerrero, Diana Alemán-González-Duhart, M. Arellano-Mendoza, S. Rojas Hernández, I. Olivares-Corichi, J. R. García Sánchez, J. T. Trujillo Ferrara, F. Tamay-Cach","doi":"10.1080/19382014.2022.2051991","DOIUrl":"https://doi.org/10.1080/19382014.2022.2051991","url":null,"abstract":"ABSTRACT The prevalence of diabetes is rapidly increasing. The current number of diagnosed cases is ~422 million, expected to reach ~640 million by 2040. Type 2 diabetes, which constitutes ~95% of the cases, is characterized by insulin resistance and a progressive loss of β-cell function. Despite intense research efforts, no treatments are yet able to cure the disease or halt its progression. Since all existing animal models of type 2 diabetes have serious drawbacks, one is needed that represents the complete pathogenesis, is low cost and non-obese, and can be developed relatively quickly. The aim of this study was to evaluate a low-cost, non-obese model of type 2 diabetes engendered by administering a daily high dose of tacrolimus (an immunosuppressant) to Wistar rats for 4 weeks. The biochemical and antioxidant markers were measured at basal and after the 4-week tacrolimus treatment. At week 4, the values of these parameters closely resembled those observed in human type 2 diabetes, including fasting blood glucose at 141.5 mg/dL, blood glucose greater than 200 mg/dL at 120 min of the glucose tolerance test, blood glucose at varied levels in the insulin tolerance test, and elevated levels of cholesterol and triglyceride. The tacrolimus treatment produced hypoinsulinemia and sustained hyperglycemia, probably explained by the alteration found in pancreatic β-cell function and morphology. This model should certainly be instrumental for evaluating possible type 2 diabetes treatments, and for designing new immunosuppressants that do not cause pancreatic damage, type 2 diabetes, or new-onset diabetes after transplantation (NODAT).","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"114 - 127"},"PeriodicalIF":2.2,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45875558","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}
引用次数: 3
Determinants and dynamics of pancreatic islet architecture 胰岛结构的决定因素和动力学
IF 2.2 4区 医学
Islets Pub Date : 2022-03-08 DOI: 10.1080/19382014.2022.2030649
Melissa T. Adams, B. Blum
{"title":"Determinants and dynamics of pancreatic islet architecture","authors":"Melissa T. Adams, B. Blum","doi":"10.1080/19382014.2022.2030649","DOIUrl":"https://doi.org/10.1080/19382014.2022.2030649","url":null,"abstract":"ABSTRACT The islets of Langerhans are highly organized structures that have species-specific, three-dimensional tissue architecture. Islet architecture is critical for proper hormone secretion in response to nutritional stimuli. Islet architecture is disrupted in all types of diabetes mellitus and in cadaveric islets for transplantation during isolation, culture, and perfusion, limiting patient outcomes. Moreover, recapitulating native islet architecture remains a key challenge for in vitro generation of islets from stem cells. In this review, we discuss work that has led to the current understanding of determinants of pancreatic islet architecture, and how this architecture is maintained or disrupted during tissue remodeling in response to normal and pathological metabolic changes. We further discuss both empirical and modeling data that highlight the importance of islet architecture for islet function.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"82 - 100"},"PeriodicalIF":2.2,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42557896","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}
引用次数: 15
Comparative analysis of reconstructed architectures from mice and human islets. 小鼠与人胰岛重构结构的比较分析。
IF 2.2 4区 医学
Islets Pub Date : 2022-01-01 DOI: 10.1080/19382014.2021.1987827
Gerardo J Félix-Martínez, J R Godínez-Fernández
{"title":"Comparative analysis of reconstructed architectures from mice and human islets.","authors":"Gerardo J Félix-Martínez,&nbsp;J R Godínez-Fernández","doi":"10.1080/19382014.2021.1987827","DOIUrl":"https://doi.org/10.1080/19382014.2021.1987827","url":null,"abstract":"<p><p>Intra-islet communication via electrical, paracrine and autocrine signals, is highly dependent on the organization of cells within the islets and is key for an adequate response to changes in blood glucose and other stimuli. In spite of the fact that relevant structural differences between mouse and human islet architectures have been described, the functional implications of these differences remain only partially understood. In this work, aiming to contribute to a better understanding of the relationship between structural and functional properties of pancreatic islets, we reconstructed human and mice islets in order to perform a structural comparison based on both morphologic and network-derived metrics. According to our results, human islets constitute a more efficient network from a connectivity viewpoint, mainly due to the higher proportion of heterotypic contacts between islet cells in comparison to mice islets.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"23-35"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/5a/KISL_14_1987827.PMC8632330.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
IsletLab: an application to reconstruct and analyze islet architectures. IsletLab:一个用于重建和分析岛屿结构的应用程序。
IF 2.2 4区 医学
Islets Pub Date : 2022-01-01 DOI: 10.1080/19382014.2021.2008742
Gerardo J Félix-Martínez
{"title":"IsletLab: an application to reconstruct and analyze islet architectures.","authors":"Gerardo J Félix-Martínez","doi":"10.1080/19382014.2021.2008742","DOIUrl":"https://doi.org/10.1080/19382014.2021.2008742","url":null,"abstract":"<p><p>The continuous interaction between experimental and theoretical work has proven to be extremely useful for the study of pancreatic cells and, recently, of pancreatic islets. This prolific interaction relies on the capability of implementing computational models and methods to derive quantitative data for the analysis and interpretation of experimental observations. In this addendum I introduce Isletlab, a multiplatform application developed to provide the research community with a user-friendly interface for the implementation of computational algorithms for the characterization and simulation of pancreatic islets.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"36-39"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/41/KISL_14_2008742.PMC8667919.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Vesiculin derived from IGF-II drives increased islet cell mass in a mouse model of pre-diabetes. 来源于IGF-II的Vesiculin在糖尿病前期小鼠模型中驱动胰岛细胞质量增加。
IF 2.2 4区 医学
Islets Pub Date : 2022-01-01 DOI: 10.1080/19382014.2021.1982326
Kate L Lee, Jacqueline F Aitken, Xun Li, Kirsten Montgomery, Huai-L Hsu, Geoffrey M Williams, Margaret A Brimble, Garth J S Cooper
{"title":"Vesiculin derived from IGF-II drives increased islet cell mass in a mouse model of pre-diabetes.","authors":"Kate L Lee,&nbsp;Jacqueline F Aitken,&nbsp;Xun Li,&nbsp;Kirsten Montgomery,&nbsp;Huai-L Hsu,&nbsp;Geoffrey M Williams,&nbsp;Margaret A Brimble,&nbsp;Garth J S Cooper","doi":"10.1080/19382014.2021.1982326","DOIUrl":"https://doi.org/10.1080/19382014.2021.1982326","url":null,"abstract":"<p><p>Pancreatic islet-cell function and volume are both key determinants of the maintenance of metabolic health. Insulin resistance and islet-cell dysfunction often occur in the earlier stages of type 2 diabetes (T2D) progression. The ability of the islet cells to respond to insulin resistance by increasing hormone output accompanied by increased islet-cell volume is key to maintaining blood glucose control and preventing further disease progression. Eventual β-cell loss is the main driver of full-blown T2D and insulin-dependency. Researchers are targeting T2D with approaches that include those aimed at enhancing the function of the patient's existing β-cell population, or replacing islet β-cells. Another approach is to look for agents that enhance the natural capacity of the β-cell population to expand. Here we aimed to study the effects of a new putative β-cell growth factor on a mouse model of pre-diabetes. We asked whether: 1) 4-week's treatment with vesiculin, a two-chain peptide derived by processing from IGF-II, had any measurable effect on pre-diabetic mice vs vehicle; and 2) whether the effects were the same in non-diabetic littermate controls. Although treatment with vesiculin did not alter blood glucose levels over this time period, there was a doubling of the Proliferating Cell Nuclear Antigen (PCNA) detectable in the islets of treated pre-diabetic but not control mice and this was accompanied by increased insulin- and glucagon-positive stained areas in the pancreatic islets.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"14-22"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/83/KISL_14_1982326.PMC8632304.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10379915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An overview of current advancements in pancreatic islet transplantation into the omentum. 胰岛移植到网膜的最新进展概述。
IF 2.2 4区 医学
Islets Pub Date : 2021-09-03 Epub Date: 2021-08-17 DOI: 10.1080/19382014.2021.1954459
Kimia Damyar, Vesta Farahmand, David Whaley, Michael Alexander, Jonathan R T Lakey
{"title":"An overview of current advancements in pancreatic islet transplantation into the omentum.","authors":"Kimia Damyar, Vesta Farahmand, David Whaley, Michael Alexander, Jonathan R T Lakey","doi":"10.1080/19382014.2021.1954459","DOIUrl":"10.1080/19382014.2021.1954459","url":null,"abstract":"<p><p>Pancreatic islet transplantation to restore insulin production in Type 1 Diabetes Mellitus patients is commonly performed by infusion of islets into the hepatic portal system. However, the risk of portal vein thrombosis or elevation of portal pressure after transplantation introduces challenges to this procedure. Thus, alternative sites have been investigated, among which the omentum represents an ideal candidate. The surgical site is easily accessible, and the tissue is highly vascularized with a large surface area for metabolic exchange. Furthermore, the ability of the omentum to host large volumes of islets represents an intriguing if not ideal site for encapsulated islet transplantation. Research on the safety and efficacy of the omentum as a transplant site focuses on the utilization of biologic scaffolds or encapsulation of islets in a biocompatible semi-permeable membrane. Currently, more clinical trials are required to better characterize the safety and efficacy of islet transplantation into the omentum.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 5-6","pages":"115-120"},"PeriodicalIF":2.2,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/5a/KISL_13_1954459.PMC8528405.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39331623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Frederick Banting's actual great idea: The role of fetal bovine islets in the discovery of insulin. 弗雷德里克·班廷的真正伟大的想法:胎牛胰岛在发现胰岛素中的作用。
IF 2.2 4区 医学
Islets Pub Date : 2021-09-03 Epub Date: 2021-09-09 DOI: 10.1080/19382014.2021.1963188
James R Wright
{"title":"Frederick Banting's actual great idea: The role of fetal bovine islets in the discovery of insulin.","authors":"James R Wright","doi":"10.1080/19382014.2021.1963188","DOIUrl":"10.1080/19382014.2021.1963188","url":null,"abstract":"<p><strong>Background: </strong>Frederick Banting approached Toronto physiology professor JJR Macleod with a way to prevent pancreatic trypsin from destroying the pancreas' internal secretion. Banting proposed to induce exocrine atrophy by ligating canine pancreatic ducts and to use extracts of islet-rich residua to treat pancreatectomized dogs. His next plan was to make extracts from fetal pancreas, which he had read was islet-rich and lacked exocrine tissue capable of making trypsin; this work has not been historically evaluated.</p><p><strong>Methods: </strong>Banting's fetal calf pancreas story is told using primary and secondary historical sources and then critically examined using both historical and recent data on species phylogeny, islet ontogeny, fetal/neonatal islet culture/transplantation, etc. Results/Discussion: Only ruminants develop dual islets populations sequentially; fetal calf pancreata, at the gestational ages Banting used, possess numerous insulin-rich giant peri-lobular islets, which credibly explain the potency of his fetal calf insulin extract. Use of non-ruminant fetal pancreata would have failed.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 5-6","pages":"121-133"},"PeriodicalIF":2.2,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/6c/KISL_13_1963188.PMC8528409.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39398410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
The Potential of Pancreatic Organoids for Diabetes Research and Therapy. 胰腺器官组织用于糖尿病研究和治疗的潜力
IF 1.9 4区 医学
Islets Pub Date : 2021-09-03 Epub Date: 2021-09-15 DOI: 10.1080/19382014.2021.1941555
Katerina Bittenglova, David Habart, Frantisek Saudek, Tomas Koblas
{"title":"The Potential of Pancreatic Organoids for Diabetes Research and Therapy.","authors":"Katerina Bittenglova, David Habart, Frantisek Saudek, Tomas Koblas","doi":"10.1080/19382014.2021.1941555","DOIUrl":"10.1080/19382014.2021.1941555","url":null,"abstract":"<p><p>The success of clinical transplantation of pancreas or isolated pancreatic islets supports the concept of cell-based cure for diabetes. One limitation is the shortage of cadaver human pancreata. The demand-supply gap could potentially be bridged by harnessing the self-renewal capacity of stem cells. Pluripotent stem cells and adult pancreatic stem cells have been explored as possible cell sources. Recently, a system for long-term culture of proposed adult pancreatic stem cells in a form of organoids was developed. Generated organoids partially mimic the architecture and cell-type composition of pancreatic tissue. Here, we review the attempts over the past decade, to utilize the organoid cell culture principles in order to identify, expand, and differentiate the adult pancreatic stem cells from different compartments of mouse and human pancreata. The development of the culture conditions, effects of specific growth factors and small molecules is discussed. The potential utility of the adult pancreatic stem cells is considered in the context of other cell sources.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 5-6","pages":"85-105"},"PeriodicalIF":1.9,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528407/pdf/KISL_13_1941555.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39417048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hnf1b-CreER causes efficient recombination of a Rosa26-RFP reporter in duct and islet δ cells. Hnf1b-CreER在导管和胰岛δ细胞中引起Rosa26-RFP报告基因的有效重组。
IF 2.2 4区 医学
Islets Pub Date : 2021-09-03 Epub Date: 2021-07-20 DOI: 10.1080/19382014.2021.1955088
Meritxell Rovira, Miguel Angel Maestro, Vanessa Grau, Jorge Ferrer
{"title":"<i>Hnf1b</i>-CreER causes efficient recombination of a Rosa26-RFP reporter in duct and islet δ cells.","authors":"Meritxell Rovira,&nbsp;Miguel Angel Maestro,&nbsp;Vanessa Grau,&nbsp;Jorge Ferrer","doi":"10.1080/19382014.2021.1955088","DOIUrl":"https://doi.org/10.1080/19382014.2021.1955088","url":null,"abstract":"<p><p>The <i>Hnf1b</i>-CreER<sup>T2</sup> BAC transgenic (Tg(Hnf1b-cre/ERT2)1Jfer) has been used extensively to trace the progeny of pancreatic ducts in developmental, regeneration, or cancer models. <i>Hnf1b</i>-CreER<sup>T2</sup> transgenics have been used to show that the cells that form the embryonic pancreas duct-like plexus are bipotent duct-endocrine progenitors, whereas adult mouse duct cells are not a common source of β cells in various regenerative settings. The interpretation of such genetic lineage tracing studies is critically dependent on a correct understanding of the cell type specificity of recombinase activity with each reporter system. We have reexamined the performance of <i>Hnf1b</i>-CreER<sup>T2</sup> with a Rosa26-RFP reporter transgene. This showed inducible recombination of up to 96% adult duct cells, a much higher efficiency than previously used reporter transgenes. Despite this high duct-cell excision, recombination in α and β cells remained very low, similar to previously used reporters. However, nearly half of somatostatin-expressing δ cells showed reporter activation, which was due to Cre expression in δ cells rather than to duct to δ cell conversions. The high recombination efficiency in duct cells indicates that the <i>Hnf1b</i>-CreER<sup>T2</sup> model can be useful for both ductal fate mapping and genetic inactivation studies. The recombination in δ cells does not modify the interpretation of studies that failed to show duct conversions to other cell types, but needs to be considered if this model is used in studies that aim to modify the plasticity of pancreatic duct cells.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 5-6","pages":"134-139"},"PeriodicalIF":2.2,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2021.1955088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39202054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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