Islets最新文献

{"title":"Culture, differentiation, and transduction of mouse E12.5 pancreatic spheres: an <i>in vitro</i> model for the secondary transition of pancreas development.","authors":"Lukas Huijbregts,&nbsp;Virginie Aiello,&nbsp;Andrea Soggia,&nbsp;Philippe Ravassard,&nbsp;Latif Rachdi,&nbsp;Raphaël Scharfmann,&nbsp;Olivier Albagli","doi":"10.1080/19382014.2020.1863723","DOIUrl":"https://doi.org/10.1080/19382014.2020.1863723","url":null,"abstract":"<p><p>During the secondary transition of rodent pancreatic development, mainly between E12.5 and E15.5 in mice, exocrine and endocrine populations differentiate from pancreatic progenitors. Here we describe an experimental system for its study <i>in vitro</i>. First, we show that spheres derived from dissociated E12.5 mouse pancreases differentiate within 7 days into most pancreatic exocrine and endocrine cell types, including beta cells. The proportion and spatial repartition of the different endocrine populations mirror those observed during normal development. Thus, dissociation and culture do not impair the developmental events affecting pancreatic progenitors during the secondary transition. Moreover, dissociated cells from mouse E12.5 pancreas were transduced with ecotropic MLV-based retroviral vectors or, though less efficiently, with a mixture of ALV(A)-based retroviral vectors and gesicles containing the TVA (Tumor Virus A) receptor. As an additional improvement, we also created a transgenic mouse line expressing TVA under the control of the 4.5 kB <i>pdx1</i> promoter (<i>pdx1</i>-TVA). We demonstrate that pancreatic progenitors from dissociated <i>pdx1</i>-TVA pancreas can be specifically transduced by ALV(A)-based retroviral vectors. Using this model, we expressed an activated mutant of the YAP transcriptional co-activator in pancreatic progenitors. These experiments indicate that deregulated YAP activity reduces endocrine and exocrine differentiation in the resulting spheres, confirming and extending previously published data. Thus, our experimental model recapitulates <i>in vitro</i> the crucial developmental decisions arising at the secondary transition and provides a convenient tool to study their genetic control.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 1-2","pages":"10-23"},"PeriodicalIF":2.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1863723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25413243","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}

{"title":"Cannabinoid receptors are differentially regulated in the pancreatic islets during the early development of metabolic syndrome.","authors":"Antonio Barajas-Martínez,&nbsp;Karina Bermeo,&nbsp;Lizbeth de la Cruz,&nbsp;Marina Martínez-Vargas,&nbsp;Ricardo Jesús Martínez-Tapia,&nbsp;David Erasmo García,&nbsp;Luz Navarro","doi":"10.1080/19382014.2020.1849927","DOIUrl":"https://doi.org/10.1080/19382014.2020.1849927","url":null,"abstract":"<p><p>The endocannabinoid system is found in tissues that regulate the glycemia, including adipose tissue, muscle, and pancreatic islets. Diet-induced metabolic syndrome changes the expression of the CB receptors in muscle, adipose tissue, and liver. However, it is poorly understood whether metabolic syndrome (MetS) affects the expression of CB receptors in pancreatic β cells. We analyzed the expression of CB receptors in pancreatic β cells under chronic high-sucrose diet (HSD)-induced MetS. Wistar rats fed an HSD as a model of MetS were used to investigate changes in cannabinoid receptors. After 8 weeks of treatment, we evaluated the appearance of the following MetS biomarkers: glucose intolerance, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and an increase in visceral adiposity. To determine the presence of CB1 and CB2 receptors in pancreatic β cells, immunofluorescence of primary cell cultures and pancreatic sections was performed. For whole-islet quantification of membrane-bound CB1 and CB2 receptors, western-blotting following differential centrifugation was conducted. Our results revealed that an HSD treatment closely mimics the alterations seen in MetS. We observed that in primary cell culture, CB1 and CB2 receptors were expressed at a higher level in pancreatic β cells compared with non-β cells. MetS resulted in a reduction of CB1 in the islet, whereas abundant CB2 was observed after the treatment. CB1 and CB2 receptors are differentially expressed in pancreatic β cells during MetS development.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 6","pages":"134-144"},"PeriodicalIF":2.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1849927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38687099","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}

{"title":"Transplantation of rat pancreatic islets vitrified-warmed on the nylon mesh device and the silk fibroin sponge disc.","authors":"Kenyu Nakayama-Iwatsuki,&nbsp;Takahiro Yamanaka,&nbsp;Jun Negishi,&nbsp;Junki Teshima,&nbsp;Yasushi Tamada,&nbsp;Masumi Hirabayashi,&nbsp;Shinichi Hochi","doi":"10.1080/19382014.2020.1849928","DOIUrl":"https://doi.org/10.1080/19382014.2020.1849928","url":null,"abstract":"<p><p>We report the adaptability of rat islets vitrified-warmed on nylon mesh (NM) device or silk fibroin (SF) sponge disc for the normalization of the blood glucose level in rat models of diabetes. One-hundred rat islets were cryopreserved according to a minimum volume cooling protocol on an NM device or a solid surface vitrification protocol on an SF sponge disc. The recovery rate (97.1% vs. 93.8%), the viability (77.9% vs. 74.4%), and the stimulation index (4.7 vs. 4.2) in glucose-stimulated insulin secretion (GSIS) assay of the post-warm islets were comparable between the NM vitrification and the SF vitrification groups. The viability and the stimulation index of the fresh control islets were identified to be 97.5% and 6.5, respectively. Eight hundred islets from the NM or the SF vitrification group or the fresh control group were transplanted beneath the kidney capsule of a streptozotocin-induced diabetic rat (blood glucose level > 350 mg/dl). Within 3 weeks after transplantation, the acquisition of euglycemia (< 200 mg/dl) was observed in recipient rats (80.0-83.3%). An intraperitoneal glucose tolerance test on Day-30 and Day-60 showed similar 2-h responses to the glucose uptake of cured rats among the compared groups. Moreover, the successful engraftment of transplants was confirmed by the Day-70 nephrectomy through the subsequent diabetes reversal and histological evaluation. Thus, large quantities of rat islets vitrified-warmed on an NM device or an SF sponge disc were proven to be fully functional both in vitro and in vivo, due to the GSIS and syngeneic transplantation, respectively.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 6","pages":"145-155"},"PeriodicalIF":2.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1849928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38687102","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}

{"title":"Reconstructing human pancreatic islet architectures using computational optimization.","authors":"Gerardo J Félix-Martínez,&nbsp;Aurelio N Mata,&nbsp;J Rafael Godínez-Fernández","doi":"10.1080/19382014.2020.1823178","DOIUrl":"https://doi.org/10.1080/19382014.2020.1823178","url":null,"abstract":"<p><p>We outline a general methodology based on computational optimization and experimental data to reconstruct human pancreatic islet architectures. By using the nuclei coordinates of islet cells obtained through DAPI staining, cell types identified by immunostaining, and cell size distributions estimated from capacitance measurements, reconstructed islets composed of non-overlapping spherical cells were obtained through an iterative optimization procedure. In all cases, the reconstructed architectures included >99% of the experimental identified cells, each of them having a radius within the experimentally reported ranges. Given the wide use of mathematical modeling for the study of pancreatic cells, and recently, of cell-cell interactions within the pancreatic islets, the methodology here proposed, also capable of identifying cell-to-cell contacts, is aimed to provide with a framework for modeling and analyzing experimentally-based pancreatic islet architectures.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 6","pages":"121-133"},"PeriodicalIF":2.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1823178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38519884","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}

{"title":"The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.","authors":"M Hoang,&nbsp;J W Joseph","doi":"10.1080/19382014.2020.1802183","DOIUrl":"https://doi.org/10.1080/19382014.2020.1802183","url":null,"abstract":"<p><p>Anaplerosis and the associated mitochondrial metabolite transporters generate unique cytosolic metabolic signaling molecules that can regulate insulin release from pancreatic β-cells. It has been shown that mitochondrial metabolites, transported by the citrate carrier (CIC), dicarboxylate carrier (DIC), oxoglutarate carrier (OGC), and mitochondrial pyruvate carrier (MPC) play a vital role in the regulation of glucose-stimulated insulin secretion (GSIS). Metabolomic studies on static and biphasic insulin secretion, suggests that several anaplerotic derived metabolites, including α-ketoglutarate (αKG), are strongly associated with nutrient regulated insulin secretion. Support for a role of αKG in the regulation of insulin secretion comes from studies looking at αKG dependent enzymes, including hypoxia-inducible factor-prolyl hydroxylases (PHDs) in clonal β-cells, and rodent and human islets. This review will focus on the possible link between defective anaplerotic-derived αKG, PHDs, and the development of type 2 diabetes (T2D).</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 5","pages":"108-119"},"PeriodicalIF":2.2,"publicationDate":"2020-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1802183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38336250","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}

{"title":"Targeting polyamine biosynthesis to stimulate beta cell regeneration in zebrafish.","authors":"Morgan A Robertson,&nbsp;Leah R Padgett,&nbsp;Jonathan A Fine,&nbsp;Gaurav Chopra,&nbsp;Teresa L Mastracci","doi":"10.1080/19382014.2020.1791530","DOIUrl":"https://doi.org/10.1080/19382014.2020.1791530","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a disease characterized by destruction of the insulin-producing beta cells. Currently, there remains a critical gap in our understanding of how to reverse or prevent beta cell loss in individuals with T1D. Previous studies in mice discovered that pharmacologically inhibiting polyamine biosynthesis using difluoromethylornithine (DFMO) resulted in preserved beta cell function and mass. Similarly, treatment of non-obese diabetic mice with the tyrosine kinase inhibitor Imatinib mesylate reversed diabetes. The promising findings from these animal studies resulted in the initiation of two separate clinical trials that would repurpose either DFMO (NCT02384889) or Imatinib (NCT01781975) and determine effects on diabetes outcomes; however, whether these drugs directly stimulated beta cell growth remained unknown. To address this, we used the zebrafish model system to determine pharmacological impact on beta cell regeneration. After induction of beta cell death, zebrafish embryos were treated with either DFMO or Imatinib. Neither drug altered whole-body growth or exocrine pancreas length. Embryos treated with Imatinib showed no effect on beta cell regeneration; however, excitingly, DFMO enhanced beta cell regeneration. These data suggest that pharmacological inhibition of polyamine biosynthesis may be a promising therapeutic option to stimulate beta cell regeneration in the setting of diabetes.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 5","pages":"99-107"},"PeriodicalIF":2.2,"publicationDate":"2020-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1791530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38195759","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}

{"title":"Melatonin protects INS-1 pancreatic β-cells from apoptosis and senescence induced by glucotoxicity and glucolipotoxicity.","authors":"Yu Hee Lee,&nbsp;Hye Sook Jung,&nbsp;Min Jeong Kwon,&nbsp;Jung Eun Jang,&nbsp;Tae Nyun Kim,&nbsp;Soon Hee Lee,&nbsp;Mi-Kyung Kim,&nbsp;Jeong Hyun Park","doi":"10.1080/19382014.2020.1783162","DOIUrl":"https://doi.org/10.1080/19382014.2020.1783162","url":null,"abstract":"<p><strong>Introduction: </strong>Melatonin is a hormone known as having very strong anti-oxidant property. Senescence is a biological state characterized by the loss of cell replication and the changes consisting of a pro-inflammatory phenotype, leading to Senescence Associated Secretory Phenotype (SASP) which is now regarded as one of the fundamental processes of many degenerative diseases. Increased cell division count induces cell senescence via DNA damage in response to elevated Reactive Oxygen Species (ROS). We wanted to test whether melatonin could reduce apoptosis and stress induced premature pancreatic β-cell senescence induced by glucotoxicity and glucolipotoxicity.</p><p><strong>Materials and method: </strong>Cultured rodent pancreatic β-cell line (INS-1 cell) was used. Glucotoxicity (HG: hyperglycemia) and glucolipotoxicity (HGP: hyperglycemia with palmitate) were induced by hyperglycemia and the addition of palmitate. The degrees of the senescence were measured by SA-β-Gal and P16^lnk4A staining along with the changes of cell viabilities, cell cycle-related protein and gene expressions, endogenous anti-oxidant defense enzymes, and Glucose Stimulated Insulin Secretion (GSIS), before and after melatonin treatment.</p><p><strong>Results: </strong>Cultured INS-1 cells in HG and HGP conditions revealed accelerated senescence, increased apoptosis, cell cycle arrest, compromised endogenous anti-oxidant defense, and impaired glucose-stimulated insulin secretion. Melatonin decreased apoptosis and expressions of proteins related to senescence, increase the endogenous anti-oxidant defense, and improved glucose-stimulated insulin secretion.</p><p><strong>Conclusion: </strong>Melatonin protected pancreatic β-cell from apoptosis, decreased expressions of the markers related to the accelerated senescence, and improved the biological deteriorations induced by glucotoxicity and glucolipotoxicity.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 4","pages":"87-98"},"PeriodicalIF":2.2,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1783162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38158802","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}

{"title":"Characterization of a mouse model of islet transplantation using MIN-6 cells.","authors":"Douglas O Sobel,&nbsp;Barath Ramasubramanian,&nbsp;Larry Mitnaul","doi":"10.1080/19382014.2020.1763719","DOIUrl":"https://doi.org/10.1080/19382014.2020.1763719","url":null,"abstract":"<p><p>Immortalized beta cells are an abundant source of insulin-producing cells. Although MIN-6 cells have similar characteristics as normal islets <i>in vitro</i>, the <i>in vivo</i> use of MIN-6 cells has not been fully described. This study characterizes <i>in vivo</i> mouse models of MIN-6 transplantation and rejection. Subcutaneous (<i>sc</i>) transplantation of MIN-6 cells in either Matrigel or HyStem-C hydrogels reduced blood sugars in nude mice and thus are good matrices for MIN-6 cells <i>in vivo</i>. NOD mice are good transplant recipients since they best rejected MIN-6 cells. MLR responses from BalbC, Black Webster, Swiss Black, C3H, and NOD mice correlated with mean blood glucose response suggesting the importance of allogeneic differences in the rejection of cells. Three days of cyclosporine administration caused no inhibition of MIN-6 cell rejection and 6 days resulted in a transient decrease in blood glucose, while daily administration inhibited rejection long term. Kinetic glucose tolerance (GTT) studies in nude mice demonstrated transplanted MIN-6 cells are close but not as effective as normal islets in controlling blood glucose and blood glucose set point for insulin release in MIN-6 cells decreases to hypoglycemic levels over time. To avoid hypoglycemia, the effect of MIN-6 cell irradiation was assessed. However, irradiation only delayed the development of hypoglycemia, not altering the final glucose set point for insulin release. In conclusion, we have characterized a mouse model for beta-cell transplantation using subcutaneous MIN-6 cells that can be used as a tool to study approaches to mitigate immune rejection.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 4","pages":"71-86"},"PeriodicalIF":2.2,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1763719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38070305","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}

{"title":"An islet maturation media to improve the development of young porcine islets during in vitro culture.","authors":"Hien Lau,&nbsp;Nicole Corrales,&nbsp;Samuel Rodriguez,&nbsp;Colleen Luong,&nbsp;Frank Zaldivar,&nbsp;Michael Alexander,&nbsp;Jonathan R T Lakey","doi":"10.1080/19382014.2020.1750933","DOIUrl":"https://doi.org/10.1080/19382014.2020.1750933","url":null,"abstract":"<p><strong>Background: </strong>The use of pancreata from pre-weaned piglets has the potential to serve as an unlimited alternative source of islets for clinical xenotransplantation. As pre-weaned porcine islets (PPIs) are immature and require prolonged culture, we developed an islet maturation media (IMM) and evaluated its effect on improving the quantity and quality of PPIs over 14 days of culture.</p><p><strong>Methods: </strong>PPIs were isolated from the pancreata of pre-weaned Yorkshire piglets (8-15 days old). Each independent islet isolation was divided for culture in either control Ham's F-10 media (n = 5) or IMM (n = 5) for 14 days. On day 3, 7 and 14 of culture, islets were assessed for islet yield, isolation index, viability, insulin content, endocrine cellular composition, differentiation of beta cells, and insulin secretion during glucose stimulation.</p><p><strong>Results: </strong>In comparison to control islets, culturing PPIs in IMM significantly increased islet yield. PPIs cultured in IMM also maintained a stable isolation index and viability throughout 14 days of culture. The insulin content, endocrine cellular composition, and differentiation of beta cells were significantly improved in PPIs cultured in IMM, which subsequently augmented their insulin secretory capacity in response to glucose challenge compared to control islets.</p><p><strong>Conclusions: </strong>Culturing PPIs in IMM increases islet yield, isolation index, viability, insulin content, endocrine cellular composition, differentiation of endocrine progenitor cells toward beta cells, and insulin secretion. Due to the improved islet quantity and quality after <i>in vitro</i> culture, the use of IMM in the culture of PPIs will assist to advance the outcomes of clinical islet xenotransplantation.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 3","pages":"41-58"},"PeriodicalIF":2.2,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1750933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37981103","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}

{"title":"Selective monitoring of insulin secretion after CRISPR interference in intact pancreatic islets despite submaximal infection.","authors":"Kaavian Shariati,&nbsp;Zachary Pappalardo,&nbsp;Deeksha G Chopra,&nbsp;Nicholas Yiv,&nbsp;Robin Sheen,&nbsp;Gregory Ku","doi":"10.1080/19382014.2020.1752072","DOIUrl":"https://doi.org/10.1080/19382014.2020.1752072","url":null,"abstract":"<p><p>Virus-mediated gene knockdown in intact pancreatic islets is technically challenging due to poor infection of the center of the islet. Because the cells that do not have knockdown have normal insulin secretion, measuring changes in insulin secretion after gene knockdown is challenging. We describe a method to monitor insulin secretion from only the beta cells with knockdown of a gene of interest in intact islets using a single lentivirus containing a guide RNA, a luciferase insulin secretion reporter and a dCas9-KRAB cassette. This method allows rapid and inexpensive monitoring of insulin secretion from only those beta cells with knockdown, circumventing the problem of incomplete islet infection.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 3","pages":"59-69"},"PeriodicalIF":2.2,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1752072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38078821","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}