Islets最新文献 - Book学术

3D evaluation of the extracellular matrix of hypoxic pancreatic islets using light sheet fluorescence microscopy. 利用光片荧光显微镜对缺氧胰岛细胞外基质进行三维评估。

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-01-24 DOI: 10.1080/19382014.2023.2298518

Matias Ramirez, Estelle Bastien, Heeyoung Chae, Pierre Gianello, Patrick Gilon, Caroline Bouzin

{"title":"3D evaluation of the extracellular matrix of hypoxic pancreatic islets using light sheet fluorescence microscopy.","authors":"Matias Ramirez, Estelle Bastien, Heeyoung Chae, Pierre Gianello, Patrick Gilon, Caroline Bouzin","doi":"10.1080/19382014.2023.2298518","DOIUrl":"10.1080/19382014.2023.2298518","url":null,"abstract":"Pancreatic islet transplantation is a promising treatment for type 1 diabetes, but the survival and function of transplanted islets are hindered by the loss of extracellular matrix (ECM) during islet isolation and by low oxygenation upon implantation. This study aimed to evaluate the impact of hypoxia on ECM using a cutting-edge imaging approach based on tissue clearing and 3D microscopy. Human and rat islets were cultured under normoxic (O2 21%) or hypoxic (O2 1%) conditions. Immunofluorescence staining targeting insulin, glucagon, CA9 (a hypoxia marker), ECM proteins (collagen 4, fibronectin, laminin), and E-cadherin (intercellular adhesion protein) was performed on fixed whole islets. The cleared islets were imaged using Light Sheet Fluorescence Microscopy (LSFM) and digitally analyzed. The volumetric analysis of target proteins did not show significant differences in abundance between the experimental groups. However, 3D projections revealed distinct morphological features that differentiated normoxic and hypoxic islets. Under normoxic conditions, ECM could be found throughout the islets. Hypoxic islets exhibited areas of scattered nuclei and central clusters of ECM proteins, indicating central necrosis. E-cadherin was absent in these areas. Our results, demonstrating a diminution of islets' functional mass in hypoxia, align with the functional decline observed in transplanted islets experiencing low oxygenation after grafting. This study provides a methodology combining tissue clearing, multiplex immunofluorescence, Light Sheet Fluorescence Microscopy, and digital image analysis to investigate pancreatic islet morphology. This 3D approach allowed us to highlight ECM organizational changes during hypoxia from a morphological perspective.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2298518"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546268","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

Decreased islet amyloid polypeptide staining in the islets of insulinoma patients. 胰岛素瘤患者胰岛淀粉样多肽染色减少。

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-07-19 DOI: 10.1080/19382014.2024.2379650

Chisaki Ishibashi, Sho Yoneda, Yukari Fujita, Shingo Fujita, Kento Mitsushio, Harutoshi Ozawa, Megu Y Baden, Takao Nammo, Junji Kozawa, Hidetoshi Eguchi, Iichiro Shimomura

引用次数: 0

EndoC-βH3 pseudoislets are suitable for intraportal transplantation in diabetic mice. EndoC-βH3 假小体适合用于糖尿病小鼠的门静脉内移植。

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-09-19 DOI: 10.1080/19382014.2024.2406041

Mengmeng Zhou, Thomas Linn, Sebastian Friedrich Petry

{"title":"EndoC-βH3 pseudoislets are suitable for intraportal transplantation in diabetic mice.","authors":"Mengmeng Zhou, Thomas Linn, Sebastian Friedrich Petry","doi":"10.1080/19382014.2024.2406041","DOIUrl":"https://doi.org/10.1080/19382014.2024.2406041","url":null,"abstract":"Background: Islet or β-cell transplantation is a therapeutical approach to substitute the insulin-producing cells which are abolished in type 1 diabetes mellitus. The shortage of human islets as well as the complicated and costly isolation process limit the application of these techniques in daily clinical practice. EndoC-βH is a human β-cell line that readily forms aggregates termed pseudoislets, providing an alternative to primary human islets or β-cells.Methods: EndoC-βH3 cells were seeded and incubated to form pseudoislets. Their insulin secretion was analyzed by ELISA and compared with cell monolayers. Pseudoislets were transplanted into streptozotocin-treated NMRi nu/nu mice. Blood glucose was monitored before and after transplantation and compared with wild types. Grafts were analyzed by immunohistology.Results: This study shows that EndoC-βH cells are able to form pseudoislets by aggregation, leading to an enhanced glucose stimulated insulin secretion in vitro. These pseudoislets were then successfully transplanted into the livers of diabetic mice and produced insulin in vitro. Blood glucose levels of the streptozocin-treated recipient mice were significantly decreased when compared to pre-transplantation and matched the levels found in control mice.Conclusion: We suggest pseudoislets aggregated from EndoC-βH cells as a valuable and promising model for islet transplantation research.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2406041"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287431","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

Characterizing the effects of Dechlorane Plus on β-cells: a comparative study across models and species. 表征除氯乙烷对β细胞的影响：一项跨模型和物种的比较研究。

IF 2.2 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-06-04 DOI: 10.1080/19382014.2024.2361996

Kyle A van Allen, Noa Gang, Myriam P Hoyeck, Ineli Perera, Dahai Zhang, Ella Atlas, Francis C Lynn, Jennifer E Bruin

{"title":"Characterizing the effects of Dechlorane Plus on β-cells: a comparative study across models and species.","authors":"Kyle A van Allen, Noa Gang, Myriam P Hoyeck, Ineli Perera, Dahai Zhang, Ella Atlas, Francis C Lynn, Jennifer E Bruin","doi":"10.1080/19382014.2024.2361996","DOIUrl":"10.1080/19382014.2024.2361996","url":null,"abstract":"Epidemiological studies consistently link environmental toxicant exposure with increased Type 2 diabetes risk. Our study investigated the diabetogenic effects of a widely used flame retardant, Dechlorane Plus (DP), on pancreatic β-cells using rodent and human model systems. We first examined pancreas tissues from male mice exposed daily to oral gavage of either vehicle (corn oil) or DP (10, 100, or 1000 μg/kg per day) and fed chow or high fat diet for 28-days in vivo. DP exposure did not affect islet size or endocrine cell composition in either diet group. Next, we assessed the effect of 48-hour exposure to vehicle (DMSO) or DP (1, 10, or 100 nM) in vitro using immortalized rat β-cells (INS-1 832/3), primary mouse and human islets, and human stem-cell derived islet-like cells (SC-islets). In INS-1 832/3 cells, DP did not impact glucose-stimulated insulin secretion (GSIS) but significantly decreased intracellular insulin content. DP had no effect on GSIS in mouse islets or SC-islets but had variable effects on GSIS in human islets depending on the donor. DP alone did not affect insulin content in mouse islets, human islets, or SC-islets, but mouse islets co-exposed to DP and glucolipotoxic (GLT) stress conditions (28.7 mM glucose + 0.5 mM palmitate) had reduced insulin content compared to control conditions. Co-exposure of mouse islets to DP + GLT amplified the upregulation of Slc30a8 compared to GLT alone. Our study highlights the importance and challenges of using different in vitro models for studying chemical toxicity.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2361996"},"PeriodicalIF":2.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11152096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247540","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

Serum from pregnant donors induces human beta cell proliferation. 怀孕供体的血清可诱导人类 beta 细胞增殖。

IF 2.2 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-03-27 DOI: 10.1080/19382014.2024.2334044

Kendra R Sylvester-Armstrong, Callie F Reeder, Andrece Powell, Matthew W Becker, D Walker Hagan, Jing Chen, Clayton E Mathews, Clive H Wasserfall, Mark A Atkinson, Robert Egerman, Edward A Phelps

{"title":"Serum from pregnant donors induces human beta cell proliferation.","authors":"Kendra R Sylvester-Armstrong, Callie F Reeder, Andrece Powell, Matthew W Becker, D Walker Hagan, Jing Chen, Clayton E Mathews, Clive H Wasserfall, Mark A Atkinson, Robert Egerman, Edward A Phelps","doi":"10.1080/19382014.2024.2334044","DOIUrl":"10.1080/19382014.2024.2334044","url":null,"abstract":"Pancreatic beta cells are among the slowest replicating cells in the human body and have not been observed to increase in number except during the fetal and neonatal period, in cases of obesity, during puberty, as well as during pregnancy. Pregnancy is associated with increased beta cell mass to meet heightened insulin demands. This phenomenon raises the intriguing possibility that factors present in the serum of pregnant individuals may stimulate beta cell proliferation and offer insights into expansion of the beta cell mass for treatment and prevention of diabetes. The primary objective of this study was to test the hypothesis that serum from pregnant donors contains bioactive factors capable of inducing human beta cell proliferation. An immortalized human beta cell line with protracted replication (EndoC-βH1) was cultured in media supplemented with serum from pregnant and non-pregnant female and male donors and assessed for differences in proliferation. This experiment was followed by assessment of proliferation of primary human beta cells. Sera from five out of six pregnant donors induced a significant increase in the proliferation rate of EndoC-βH1 cells. Pooled serum from the cohort of pregnant donors also increased the rate of proliferation in primary human beta cells. This study demonstrates that serum from pregnant donors stimulates human beta cell proliferation. These findings suggest the existence of pregnancy-associated factors that can offer novel avenues for beta cell regeneration and diabetes prevention strategies. Further research is warranted to elucidate the specific factors responsible for this effect.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2334044"},"PeriodicalIF":2.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293513","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

Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy. Neuregulin 4通过激活mTOR介导的自噬减轻脂肪毒性诱导的胰腺β细胞凋亡

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-11-14 DOI: 10.1080/19382014.2024.2429854

Biao Zhu, Lei Sun, Junyao Tong, Yan Ding, Yanbo Shan, Mingjuan He, Xiaoyu Tian, Wen Mei, Lisheng Zhao, Ying Wang

{"title":"Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy.","authors":"Biao Zhu, Lei Sun, Junyao Tong, Yan Ding, Yanbo Shan, Mingjuan He, Xiaoyu Tian, Wen Mei, Lisheng Zhao, Ying Wang","doi":"10.1080/19382014.2024.2429854","DOIUrl":"10.1080/19382014.2024.2429854","url":null,"abstract":"Neuregulin 4 (Nrg4) is a brown fat-enriched endocrine factor that ameliorates lipid metabolism disorders. Autophagy is critical for pancreatic β-cell to counteract lipotoxicity-induced apoptosis. This study aimed at exploring whether Nrg4 attenuates lipotoxicity-induced β-cell apoptosis by regulating autophagy. The mouse pancreatic β-cell line MIN6 was cultured in palmitic acid (PA) with or without Nrg4 administration. Apoptosis rate, together with anti-apoptotic and pro-apoptotic protein levels, was investigated. Autophagic flux and autophagy-related protein levels along with related signaling pathways that regulate autophagy were also evaluated. Results showed that Nrg4 decreased PA-induced MIN6 apoptosis, enhanced anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression and reduced pro-apoptotic proteins Bcl-2-associated X protein (Bax) and cleaved-caspase 3 expressions. Autophagy levels in MIN6 also decreased with PA treatment and Nrg4 administration reactivated autophagy. Further, Nrg4 administration activated autophagy via the mammalian target of rapamycin (mTOR) signaling pathway. In addition, when the mTOR pathway was stimulated or autophagy was suppressed, the beneficial effects of Nrg4 administration on MIN6 apoptosis were diminished. These results imply that Nrg4 administration attenuates MIN6 apoptosis by promoting mTOR-dependent autophagy and thus may lead to a new therapeutic method for type 2 diabetes mellitus (T2DM).","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2429854"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620703","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

Human research islet cell culture outcomes at the Alberta Diabetes Institute IsletCore. 阿尔伯塔糖尿病研究所胰岛核心的人类研究胰岛细胞培养成果。

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-08-04 DOI: 10.1080/19382014.2024.2385510

James G Lyon, Alice Lj Carr, Nancy P Smith, Braulio Marfil-Garza, Aliya F Spigelman, Austin Bautista, Doug O'Gorman, Tatsuya Kin, Am James Shapiro, Peter A Senior, Patrick E MacDonald

{"title":"Human research islet cell culture outcomes at the Alberta Diabetes Institute IsletCore.","authors":"James G Lyon, Alice Lj Carr, Nancy P Smith, Braulio Marfil-Garza, Aliya F Spigelman, Austin Bautista, Doug O'Gorman, Tatsuya Kin, Am James Shapiro, Peter A Senior, Patrick E MacDonald","doi":"10.1080/19382014.2024.2385510","DOIUrl":"10.1080/19382014.2024.2385510","url":null,"abstract":"Human islets from deceased organ donors have made important contributions to our understanding of pancreatic endocrine function and continue to be an important resource for research studies aimed at understanding, treating, and preventing diabetes. Understanding the impacts of isolation and culture upon the yield of human islets for research is important for planning research studies and islet distribution to distant laboratories. Here, we examine islet isolation and cell culture outcomes at the Alberta Diabetes Institute (ADI) IsletCore (n = 197). Research-focused isolations typically have a lower yield of islet equivalents (IEQ), with a median of 252,876 IEQ, but a higher purity (median 85%) than clinically focused isolations before culture. The median recovery of IEQs after culture was 75%, suggesting some loss. This was associated with a shift toward smaller islet particles, indicating possible islet fragmentation, and occurred within 24 h with no further loss after longer periods of culture (up to 136 h). No overall change in stimulation index as a measure of islet function was seen with culture time. These findings were replicated in a representative cohort of clinical islet preparations from the Clinical Islet Transplant Program at the University of Alberta. Thus, loss of islets occurs within 24 h of isolation, and there is no further impact of extended culture prior to islet distribution for research.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2385510"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889263","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

Small RNA-Seq and real time rt-qPCR reveal islet miRNA released under stress conditions. 小 RNA-Seq 和实时 rt-qPCR 揭示了应激条件下释放的胰岛 miRNA。

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-08-18 DOI: 10.1080/19382014.2024.2392343

Bssam Aljani, Annett Lindner, Marc Weigelt, Min Zhao, Virag Sharma, Ezio Bonifacio, Peter Jones, Anne Eugster

{"title":"Small RNA-Seq and real time rt-qPCR reveal islet miRNA released under stress conditions.","authors":"Bssam Aljani, Annett Lindner, Marc Weigelt, Min Zhao, Virag Sharma, Ezio Bonifacio, Peter Jones, Anne Eugster","doi":"10.1080/19382014.2024.2392343","DOIUrl":"10.1080/19382014.2024.2392343","url":null,"abstract":"Replacement of beta cells through transplantation is a potential therapeutic approach for individuals with pancreas removal or poorly controllable type 1 diabetes. However, stress and death of beta cells pose significant challenges. Circulating miRNA has emerged as potential biomarkers reflecting early beta cell stress and death, allowing for timely intervention. The aim of this study was to identify miRNAs as potential biomarkers for beta cell health. Literature review combined with small RNA sequencing was employed to select islet-enriched miRNA. The release of those miRNA was assessed by RT-qPCR in vivo, using a streptozotocin induced diabetes mouse model and in vitro, through mouse and human islets exposed to varying degrees of hypoxic and cytokine stressors. Utilizing the streptozotocin induced model, we identified 18 miRNAs out of 39 candidate islet-enriched miRNA to be released upon islet stress in vivo. In vitro analysis of culture supernatants from cytokine and/or hypoxia stressed islets identified the release of 45 miRNAs from mouse and 8 miRNAs from human islets. Investigation into the biological pathways targeted by the cytokine- and/or hypoxia-induced miRNA suggested the involvement of MAPK and PI3K-Akt signaling pathways in both mouse and human islets. We have identified miRNAs associated with beta cell health and stress. The findings allowed us to propose a panel of 47 islet-related human miRNA that is potentially valuable for application in clinical contexts of beta cell transplantation and presymptomatic early-stage type 1 diabetes.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2392343"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995747","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

β cell acetate production and release are negligible β 细胞醋酸盐的产生和释放可以忽略不计

IF 2.2 4区医学

Islets Pub Date : 2024-04-12 DOI: 10.1080/19382014.2024.2339558

Kai Xu, Chioma Nnyamah, Nupur Pandya, Nadia Sweis, Irene Corona-Avila, Medha Priyadarshini, Barton Wicksteed, Brian T. Layden

引用次数: 0

Beta cell primary cilia mediate somatostatin responsiveness via SSTR3. 细胞原代纤毛通过SSTR3介导生长抑素反应。

IF 2.2 4区医学

Islets Pub Date : 2023-12-31 DOI: 10.1080/19382014.2023.2252855

Samantha E Adamson, Zipeng A Li, Jing W Hughes

{"title":"Beta cell primary cilia mediate somatostatin responsiveness via SSTR3.","authors":"Samantha E Adamson, Zipeng A Li, Jing W Hughes","doi":"10.1080/19382014.2023.2252855","DOIUrl":"10.1080/19382014.2023.2252855","url":null,"abstract":"Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address in this study via the ciliary somatostatin receptor 3 (SSTR3). Primary cilia are membrane organelles that act as signaling hubs in islets by virtue of their subcellular location and enrichment in signaling proteins such as G-protein coupled receptors (GPCRs). We show that SSTR3, a ciliary GPCR, mediates somatostatin suppression of insulin secretion in mouse islets. Quantitative analysis of calcium flux using a mouse model of genetically encoded beta cell-specific GCaMP6f calcium reporter shows that somatostatin signaling alters beta cell calcium flux after physiologic glucose stimulation, an effect that depends on endogenous SSTR3 expression and the presence of intact primary cilia on beta cells. Comparative in vitro studies using SSTR isoform antagonists demonstrate a role for SSTR3 in mediating somatostatin regulation of insulin secretion in mouse islets. Our findings support a model in which ciliary SSTR3 mediates a distinct pathway of delta-to-beta cell regulatory crosstalk and may serve as a target for paracrine modulation.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"15 1","pages":"2252855"},"PeriodicalIF":2.2,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178767","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