Cellular and Molecular Gastroenterology and Hepatology最新文献

{"title":"SIRT1 Stabilizes β-TrCP1 to Inhibit Snail1 Expression in Maintaining Intestinal Epithelial Integrity to Alleviate Colitis","authors":"Liang Wang ,&nbsp;Jinsong Li ,&nbsp;Mingshan Jiang ,&nbsp;Yue Luo ,&nbsp;Xiaoke Xu ,&nbsp;Juan Li ,&nbsp;Yang Pan ,&nbsp;Hu Zhang ,&nbsp;Zhi-Xiong Jim Xiao ,&nbsp;Yang Wang","doi":"10.1016/j.jcmgh.2024.05.002","DOIUrl":"10.1016/j.jcmgh.2024.05.002","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to inflammatory bowel disease (IBD). The NAD⁺-dependent deacetylase SIRT1 is implicated in inflammation and the pathologic process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity.</p></div><div><h3>Methods</h3><p>The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and wild-type mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes was analyzed. Intestinal permeability was measured by FITC-dextran and cytokines expression was analyzed by quantitative polymerase chain reaction. The expression of the cell junction–related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of nicotinamide mononucleotide in DSS-induced mice colitis were investigated. Correlations of the SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed.</p></div><div><h3>Results</h3><p>Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. The activation of SIRT1 by nicotinamide mononucleotide bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS downregulates SiRT1 expression, leading to destabilization of β-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD.</p></div><div><h3>Conclusions</h3><p>SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the β-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001085/pdfft?md5=ec34af7822631db47d221e53a4b22e02&pid=1-s2.0-S2352345X24001085-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover - CDKN2A/p16 and KRAS Synergize in Barrett’s Esophagus Dysplasia","authors":"","doi":"10.1016/S2352-345X(24)00065-1","DOIUrl":"https://doi.org/10.1016/S2352-345X(24)00065-1","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000651/pdfft?md5=95d2f2e2521dbfb8b9b24d1cf09c2d4d&pid=1-s2.0-S2352345X24000651-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140557717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial-Fibroblast Crosstalk in Eosinophilic Esophagitis","authors":"Amanda B. Muir ,&nbsp;Tatiana A. Karakasheva ,&nbsp;Kelly A. Whelan","doi":"10.1016/j.jcmgh.2024.01.020","DOIUrl":"10.1016/j.jcmgh.2024.01.020","url":null,"abstract":"<div><p>Eosinophilic esophagitis (EoE) is an emerging form of food allergy that exerts a significant clinical and financial burden worldwide. EoE is clinically characterized by eosinophil-rich inflammatory infiltrates in esophageal mucosa and esophageal dysfunction. Remodeling events in esophageal epithelium and lamina propria also frequently occur in patients with EoE. Because subepithelial fibrosis is associated with esophageal stricture, the most severe consequence of EoE, there exists an urgent need for a deeper understanding of the molecular mechanisms mediating fibrosis in EoE. Here, we review emerging evidence from experimental model systems that implicates crosstalk between esophageal epithelial cells and underlying stromal cells in EoE fibrosis. We further discuss implications for epithelial-stromal interaction with regard to EoE patient care and propose future directions that may be pursued to further the understanding of epithelial-stromal crosstalk in EoE pathobiology.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000237/pdfft?md5=d1bf96f096f826b703b4ba9002f49572&pid=1-s2.0-S2352345X24000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the Roles of Cancer-Associated Fibroblasts in Pancreatic Cancer","authors":"Ralph Francescone ,&nbsp;Howard C. Crawford ,&nbsp;Debora Barbosa Vendramini-Costa","doi":"10.1016/j.jcmgh.2024.01.022","DOIUrl":"10.1016/j.jcmgh.2024.01.022","url":null,"abstract":"<div><p>Bearing a dismal 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is a challenging disease that features a unique fibroinflammatory tumor microenvironment. As major components of the PDAC tumor microenvironment, cancer-associated fibroblasts are still poorly understood and their contribution to the several hallmarks of PDAC, such as resistance to therapies, immunosuppression, and high incidence of metastasis, is likely underestimated. There have been encouraging advances in the understanding of these fascinating cells, but many controversies remain, leaving the field still actively exploring the full scope of their contributions in PDAC progression. Here we pose several important considerations regarding PDAC cancer-associated fibroblast functions. We posit that transcriptomic analyses be interpreted with caution, when aiming to uncover the functional contributions of these cells. Moreover, we propose that normalizing these functions, rather than eliminating them, will provide the opportunity to enhance therapeutic response. Finally, we propose that cancer-associated fibroblasts should not be studied in isolation, but in conjunction with its extracellular matrix, because their respective functions are coordinated and concordant.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000250/pdfft?md5=f1bd4e8db1394296f5770ca91b13316f&pid=1-s2.0-S2352345X24000250-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stromal Niche Signals That Orchestrate Intestinal Regeneration","authors":"Helen E. Abud ,&nbsp;Shanika L. Amarasinghe ,&nbsp;Diana Micati ,&nbsp;Thierry Jardé","doi":"10.1016/j.jcmgh.2024.02.003","DOIUrl":"10.1016/j.jcmgh.2024.02.003","url":null,"abstract":"<div><p>Stromal cell populations have a central role in providing signals that support the maintenance, differentiation, and function of the intestinal epithelium. The behavior and fate of epithelial cells is directed by the spatial organization of stromal cells that either sustain stem and progenitor cell identity or drive differentiation. A combination of single-cell analyses, mouse models, and organoid coculture assays have provided insight into the diversity of signals delivered by stromal cells. Signaling gradients are established and fine-tuned by the expression of signaling agonists and antagonists along the crypt-villus axis. On epithelial injury, there are disruptions to the abundance and organization of stromal populations. There are also distinct changes in the signals originating from these cells that impact remodeling of the epithelium. How these signals coordinate to mediate epithelial repair or sustain tissue injury in inflammatory bowel diseases is beginning to emerge. Understanding of these processes may lead to opportunities to target stromal cell populations as a strategy to modify disease states.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000316/pdfft?md5=8c4c0d9049eefe0f57825e81339fb61b&pid=1-s2.0-S2352345X24000316-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interleukin 33–T Helper 2 Cell Axis Promotes Human Liver Fibrosis","authors":"Isabella Lurje,&nbsp;Frank Tacke","doi":"10.1016/j.jcmgh.2024.01.004","DOIUrl":"10.1016/j.jcmgh.2024.01.004","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000043/pdfft?md5=68e1b801e29bd6ca126808e22fa66615&pid=1-s2.0-S2352345X24000043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel CRISPR/Cas9-mediated Mouse Model of Colon Carcinogenesis","authors":"","doi":"10.1016/j.jcmgh.2024.101390","DOIUrl":"10.1016/j.jcmgh.2024.101390","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Human sporadic colorectal cancer (CRC) results from a multistep pathway with sequential acquisition of specific genetic mutations in the colorectal epithelium. Modeling CRC <em>in vivo</em> is critical for understanding the tumor microenvironment. To accurately recapitulate human CRC pathogenesis, mouse models must include these multi-step genetic abnormalities. The aim of this study was to generate a sporadic CRC model that more closely mimics this multi-step process and to use this model to study the role of a novel Let7 target PLAGL2 in CRC pathogenesis.</div></div><div><h3>Methods</h3><div>We generated a CRISPR/Cas9 somatic mutagenesis mouse model that is inducible and multiplexed for simultaneous inactivation of multiple genes involved in CRC pathogenesis. We used both a doxycycline-inducible transcriptional activator and a doxycycline-inactivated transcriptional repressor to achieve tight, non-leaky expression of the Cas9 nickase. This mouse has transgenic expression of multiple guide RNAs to induce sporadic inactivation in the gut epithelium of 4 tumor suppressor genes commonly mutated in CRC, <em>Apc, Pten</em>, <em>Smad4</em>, and <em>Trp53</em>. These were crossed to <em>Vil-LCL-PLAGL2</em> mice, which have Cre-inducible overexpression of PLAGL2 in the gut epithelium.</div></div><div><h3>Results</h3><div>These mice exhibited random somatic mutations in all 4 targeted tumor suppressor genes, resulting in multiple adenomas and adenocarcinomas in the small bowel and colon. Crosses with <em>Vil-LCL-PLAGL2</em> mice demonstrated that gut-specific PLAGL2 overexpression increased colon tumor growth.</div></div><div><h3>Conclusions</h3><div>This conditional model represents a new CRISPR/Cas9-mediated mouse model of colorectal carcinogenesis. These mice can be used to investigate the role of novel, previously uncharacterized genes in CRC, in the context of multiple commonly mutated tumor suppressor genes and thus more closely mimic human CRC pathogenesis.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001450/pdfft?md5=daeaeb5124d1ccf33502431754817647&pid=1-s2.0-S2352345X24001450-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial-Dependent Recruitment of Immature Myeloid Cells Promotes Intestinal Regeneration","authors":"Zhengyu Jiang ,&nbsp;Quin T. Waterbury ,&nbsp;Ermanno Malagola ,&nbsp;Na Fu ,&nbsp;Woosook Kim ,&nbsp;Yosuke Ochiai ,&nbsp;Feijing Wu ,&nbsp;Chandan Guha ,&nbsp;Carrie J. Shawber ,&nbsp;Kelley S. Yan ,&nbsp;Timothy C. Wang","doi":"10.1016/j.jcmgh.2023.10.007","DOIUrl":"10.1016/j.jcmgh.2023.10.007","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>The intestinal epithelium functions both in nutrient absorption and as a barrier, separating the luminal contents from a network of vascular, fibroblastic, and immune cells underneath. After injury to the intestine, multiple cell populations cooperate to drive regeneration of the mucosal barrier, including lymphatic endothelial cells (LECs). A population of granulocytic immature myeloid cells (IMCs), marked by <em>Hdc</em>, participate in regeneration of multiple organs such as the colon and central nervous system, and their contribution to intestinal regeneration was investigated.</p></div><div><h3>Methods</h3><p>By using male and female histidine decarboxylase (Hdc) green fluorescent reporter (GFP) mice, we investigated the role of Hdc⁺ IMCs in intestinal regeneration after exposure to 12 Gy whole-body irradiation. The movement of IMCs was analyzed using flow cytometry and immunostaining. Ablation of Hdc⁺ cells using the Hdc^CreERT2 tamoxifen-inducible recombinase Cre system, conditional knockout of Prostaglandin-endoperoxidase synthase 2 (<em>Ptgs2</em><em>)</em> in Hdc⁺ cells using Hdc^Cre; Ptgs2 floxed mice, and visualization of LECs using Prox1^tdTomato mice also was performed. The role of microbial signals was investigated by knocking down mice gut microbiomes using antibiotic cocktail gavages.</p></div><div><h3>Results</h3><p>We found that Hdc⁺ IMCs infiltrate the injured intestine after irradiation injury and promote epithelial regeneration in part by modulating LEC activity. Hdc⁺ IMCs express <em>Ptgs2</em> (encoding cyclooxygenase-2/COX-2), and enables them to produce prostaglandin E₂. Prostaglandin E₂ acts on the prostaglandin E₂ receptor 4 receptor (EP4) on LECs to promote lymphangiogenesis and induce the expression of proregenerative factors including R-spondin 3. Depletion of gut microbes leads to reduced intestinal regeneration by impaired recruitment of IMCs.</p></div><div><h3>Conclusions</h3><p>Altogether, our results unveil a critical role for IMCs in intestinal repair by modulating LEC activity and implicate gut microbes as mediators of intestinal regeneration.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X23001868/pdfft?md5=cd8dff9258af4c6988d6e5fbf33d2526&pid=1-s2.0-S2352345X23001868-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Genes Core to ERAD, Macroautophagy and Lysosomal Degradation Pathways Participate in the Proteostasis Response in α1-Antitrypsin Deficiency","authors":"Jie Li ,&nbsp;Francesca Moretti ,&nbsp;Tunda Hidvegi ,&nbsp;Sanja Sviben ,&nbsp;James A.J. Fitzpatrick ,&nbsp;Hemalatha Sundaramoorthi ,&nbsp;Stephen C. Pak ,&nbsp;Gary A. Silverman ,&nbsp;Britta Knapp ,&nbsp;Ireos Filipuzzi ,&nbsp;John Alford ,&nbsp;John Reece-Hoyes ,&nbsp;Florian Nigsch ,&nbsp;Leon O. Murphy ,&nbsp;Beat Nyfeler ,&nbsp;David H. Perlmutter","doi":"10.1016/j.jcmgh.2024.02.006","DOIUrl":"10.1016/j.jcmgh.2024.02.006","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>In the classic form of α1-antitrypsin deficiency (ATD), the misfolded α1-antitrypsin Z (ATZ) variant accumulates in the endoplasmic reticulum (ER) of liver cells. A gain-of-function proteotoxic mechanism is responsible for chronic liver disease in a subgroup of homozygotes. Proteostatic response pathways, including conventional endoplasmic reticulum–associated degradation and autophagy, have been proposed as the mechanisms that allow cellular adaptation and presumably protection from the liver disease phenotype. Recent studies have concluded that a distinct lysosomal pathway called endoplasmic reticulum–to-lysosome completely supplants the role of the conventional macroautophagy pathway in degradation of ATZ. Here, we used several state-of-the-art approaches to characterize the proteostatic responses more fully in cellular systems that model ATD.</p></div><div><h3>Methods</h3><p>We used clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome editing coupled to a cell selection step by fluorescence-activated cell sorter to perform screening for proteostasis genes that regulate ATZ accumulation and combined that with selective genome editing in 2 other model systems.</p></div><div><h3>Results</h3><p>Endoplasmic reticulum–associated degradation genes are key early regulators and multiple autophagy genes, from classic as well as from ER-to-lysosome and other newly described ER-phagy pathways, participate in degradation of ATZ in a manner that is temporally regulated and evolves as ATZ accumulation persists. Time-dependent changes in gene expression are accompanied by specific ultrastructural changes including dilation of the ER, formation of globular inclusions, budding of autophagic vesicles, and alterations in the overall shape and component parts of mitochondria.</p></div><div><h3>Conclusions</h3><p>Macroautophagy is a critical component of the proteostasis response to cellular ATZ accumulation and it becomes more important over time as ATZ synthesis continues unabated. Multiple subtypes of macroautophagy and nonautophagic lysosomal degradative pathways are needed to respond to the high concentrations of misfolded protein that characterizes ATD and these pathways are attractive candidates for genetic variants that predispose to the hepatic phenotype.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000341/pdfft?md5=1d5ceb08da9a2307e43d988fca289133&pid=1-s2.0-S2352345X24000341-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Nutraceutical Mechanistic Model Receives a Gut Check","authors":"Nicholas J. Hand","doi":"10.1016/j.jcmgh.2024.02.007","DOIUrl":"10.1016/j.jcmgh.2024.02.007","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000353/pdfft?md5=e9a1a7509f58ccf4bc710153c220cb1f&pid=1-s2.0-S2352345X24000353-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}