American journal of physiology. Gastrointestinal and liver physiology最新文献

{"title":"Intraduodenal fecal microbiota transplantation ameliorates gut atrophy and cholestasis in a novel parenteral nutrition piglet model.","authors":"Chandrashekhara Manithody, Christine Denton, Shaurya Mehta, Jasmine Carter, Kento Kurashima, Ashlesha Bagwe, Marzena Swiderska-Syn, Miguel Guzman, Sherri Besmer, Sonali Jain, Matthew McHale, Kamran Qureshi, Mustafa Nazzal, Yasar Caliskan, John Long, Chien-Jung Lin, Chelsea Hutchinson, Aaron C Ericsson, Ajay Kumar Jain","doi":"10.1152/ajpgi.00012.2024","DOIUrl":"10.1152/ajpgi.00012.2024","url":null,"abstract":"<p><p>Total parenteral nutrition (TPN) provides lifesaving nutritional support intravenously; however, it is associated with significant side effects. Given gut microbial alterations noted with TPN, we hypothesized that transferring fecal microbiota from healthy controls would restore gut-systemic signaling in TPN and mitigate injury. Using our novel ambulatory model (US Patent: US 63/136,165), 31 piglets were randomly allocated to enteral nutrition (EN), TPN only, TPN + antibiotics (TPN-A), or TPN + intraduodenal fecal microbiota transplant (TPN + FMT) for 14 days. Gut, liver, and serum were assessed through histology, biochemistry, and qPCR. Stool samples underwent 16 s rRNA sequencing. Permutational multivariate analysis of variance, Jaccard, and Bray-Curtis metrics were performed. Significant bilirubin elevation in TPN and TPN-A versus EN (<i>P</i> < 0.0001) was prevented with FMT. IFN-G, TNF-α, IL-β, IL-8, and lipopolysaccharide (LPS) were significantly higher in TPN (<i>P</i> = 0.009, P = 0.001, <i>P</i> = 0.043, <i>P</i> = 0.011, <i>P</i> < 0.0001), with preservation upon FMT. Significant gut atrophy by villous-to-crypt ratio in TPN (<i>P</i> < 0.0001) and TPN-A (<i>P</i> = 0.0001) versus EN was prevented by FMT (<i>P</i> = 0.426 vs. EN). Microbiota profiles using principal coordinate analysis demonstrated significant FMT and EN overlap, with the largest separation in TPN-A followed by TPN, driven primarily by Firmicutes and Fusobacteria. TPN-altered gut barrier was preserved upon FMT; upregulated cholesterol 7 α-hydroxylase and bile salt export pump in TPN and TPN-A and downregulated fibroblast growth factor receptor 4, EGF, farnesoid X receptor, and Takeda G Protein-coupled Receptor 5 (TGR5) versus EN was prevented by FMT. This study provides novel evidence of prevention of gut atrophy, liver injury, and microbial dysbiosis with intraduodenal FMT, challenging current paradigms into TPN injury mechanisms and underscores the importance of gut microbes as prime targets for therapeutics and drug discovery.<b>NEW & NOTEWORTHY</b> Intraduodenal fecal microbiota transplantation presents a novel strategy to mitigate complications associated with total parenteral nutrition (TPN), highlighting gut microbiota as a prime target for therapeutic and diagnostic approaches. These results from a highly translatable model provide hope for TPN side effect mitigation for thousands of chronically TPN-dependent patients.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal microbial transplants as investigative tools in cancer.","authors":"Margaret S Bohm, Arvind V Ramesh, Joseph F Pierre, Katherine L Cook, E Angela Murphy, Liza Makowski","doi":"10.1152/ajpgi.00171.2024","DOIUrl":"10.1152/ajpgi.00171.2024","url":null,"abstract":"<p><p>The gut microbiome plays a critical role in the development, progression, and treatment of cancer. As interest in microbiome-immune-cancer interactions expands, the prevalence of fecal microbial transplant (FMT) models has increased proportionally. However, current literature does not provide adequate details or consistent approaches to allow for necessary rigor and experimental reproducibility. In this review, we evaluate key studies using FMT to investigate the relationship between the gut microbiome and various types of cancer. In addition, we will discuss the common pitfalls of these experiments and methods for improved standardization and validation as the field uses FMT with greater frequency. Finally, this review focuses on the impacts of the gut and extraintestinal microbes, prebiotics, probiotics, and postbiotics in cancer risk and response to therapy across a variety of tumor types.<b>NEW & NOTEWORTHY</b> The microbiome impacts the onset, progression, and therapy response of certain types of cancer. Fecal microbial transplants (FMTs) are an increasingly prevalent tool to test these mechanisms that require standardization by the field.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feeding intolerance after pediatric cardiac surgery is associated with dysbiosis, barrier dysfunction, and reduced short-chain fatty acids.","authors":"Jacob Owens, Haowen Qiu, Cole Knoblich, Lisa Gerjevic, Jacques Izard, Linda Xu, Junghyae Lee, Sai Sundeep Kollala, Daryl J Murry, Jean Jack Riethoven, Jesse A Davidson, Amar B Singh, Ali Ibrahimiye, Laura Ortmann, Jeffrey D Salomon","doi":"10.1152/ajpgi.00151.2024","DOIUrl":"10.1152/ajpgi.00151.2024","url":null,"abstract":"<p><p>Congenital heart disease (CHD) is the most common birth defect, occurring in roughly 40,000 U.S. births annually. Malnutrition and feeding intolerance (FI) in CHD range from 30% to 42% and are associated with longer hospitalization and increased mortality. Cardiopulmonary bypass (CPB) required for surgical repair of CHD induces a systemic inflammatory response worsening intestinal dysbiosis and leading to intestinal epithelial barrier dysfunction (EBD), possibly contributing to postoperative FI. The objective of this study was to determine the relationship of postoperative FI with intestinal microbiome, short-chain fatty acids (SCFAs), and EBD in pediatric CHD after cardiac surgery. This was a prospective study of patients aged 0-15 years undergoing cardiac surgery with CPB. Samples were collected preoperatively and postoperatively to evaluate the gut microbiome, plasma EBD markers, short-chain fatty acids (SCFAs), and plasma cytokines. Clinical data were collected to calculate a FI score and evaluate patient status postoperatively. We enrolled 26 CPB patients and identified FI (<i>n</i> = 13). Patients with FI had unique microbial shifts with the reduced SCFA-producing organisms <i>Rothia</i>, <i>Clostridium innocuum</i>, and <i>Intestinimonas</i>. Patients who developed FI had associated elevations in the plasma EBD markers claudin-2 (<i>P</i> < 0.05), claudin-3 (<i>P</i> < 0.01), and fatty acid binding protein (<i>P</i> < 0.01). Patients with FI had reduced plasma and stool SCFAs. Mediation analysis showed the microbiome functional shift was associated with reductions in stool butyric and propionic acid in patients with FI. In conclusion, we provide novel evidence that intestinal dysbiosis, markers of EBD, and SCFA depletion are associated with FI. These data will help identify mechanisms and therapeutics to improve clinical outcomes following pediatric cardiac surgery.<b>NEW & NOTEWORTHY</b> Feeding intolerance contributes to postoperative morbidity following pediatric cardiac surgery. The intestinal microbiome and milieu play a vital role in gut function. Short-chain fatty acids are gut and cardioprotective metabolites produced by commensal bacteria and help maintain appropriate barrier function. Depletion of these metabolites and barrier dysfunction contribute to postoperative feeding intolerance following cardiac surgery. Identifying mechanistic targets to improve the intestinal milieu with the goal of improved nutrition and clinical outcomes is critical.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased expression of DRA (<i>SLC26A3</i>) by a p38-driven IL-1α response contributes to diarrheal disease following in vivo challenge with <i>Brachyspira</i> spp.","authors":"Nitin Challa, Cole B Enns, Brandon A Keith, John C S Harding, Matthew E Loewen","doi":"10.1152/ajpgi.00049.2023","DOIUrl":"10.1152/ajpgi.00049.2023","url":null,"abstract":"<p><p>In this study, we uncovered the novel mechanism of IL-1α-mediated downregulated in adenoma (DRA) (<i>SLC26A3</i>) downregulation in the context of <i>Brachyspira</i> spp.<i>-</i>induced malabsorptive diarrhea. Experimentally infected pigs with <i>Brachyspira</i> spp. had significantly reduced DRA expression in the colon accompanied by IL-1α upregulation. This response was recapitulated in vitro by exposing Caco-2 cells to either <i>Brachyspira</i> lysate or IL-1α. Both p38 and MAPK-activated protein kinase 2 (MAPKAPK-2 also referred as MK-2) showed an increased phosphorylation after exposure to either. SB203580 application, a p38 inhibitor blocked the MK-2 phosphorylation and attenuated the DRA and IL-1α response to both lysate and IL-1α. Exposure to IL-1 receptor antagonist (IL-1RA) produced a similar response. In addition, exposure of cells to either of these blockers without IL-1α or lysate results in increased DRA and decreased IL-1α expression, revealing that DRA needs IL-1α signaling for basal physiological expression. Dual inhibition with both blockers completely inhibited the effect from IL-1α while significantly attenuating the response from <i>Brachyspira</i> lysate, suggesting a minor contribution from another pathway. Together this demonstrates that <i>Brachyspira</i> activates p38 MAPK signaling driving IL-1α expression, which activates IL-1R1 causing DRA downregulation while also driving upregulation of IL-1α through p38 in a positive feedback mechanism. In conclusion, we elucidated a major pathway involved in DRA downregulation and its role in <i>Brachyspira</i>-induced diarrhea. In addition, these observations will aid in our understanding of other inflammatory and infectious diarrhea conditions.<b>NEW & NOTEWORTHY</b> The diarrheal disease caused by the two infectious spirochete spp. <i>B. hyodysenteriae</i> and <i>B. hampsonii</i> reduced the expression of DRA (<i>SLC26A3</i>), a major Cl^-/HCO^-₃ exchanger involved in Cl^- absorption. This is attributed to the upregulation of IL-1α driven by p38 MAPK. This work also describes a potential new mechanism in inflammatory diseases while showing the importance of IL-1α in maintaining DRA levels.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amniotic fluid modifies esophageal epithelium differentiation and inflammatory responses.","authors":"Mark Rochman, Andrea M Klinger, Julie M Caldwell, Yoel Sadovsky, Marc E Rothenberg","doi":"10.1152/ajpgi.00197.2024","DOIUrl":"10.1152/ajpgi.00197.2024","url":null,"abstract":"<p><p>The interplay between genetic and environmental factors during pregnancy can predispose to inflammatory diseases postnatally, including eosinophilic esophagitis (EoE), a chronic allergic disease triggered by food. Herein, we examined the effects of amniotic fluid (AF) on esophageal epithelial differentiation and responsiveness to proallergic stimuli. Multiplex analysis of AF revealed the expression of 66 cytokines, whereas five cytokines including IL-4 and thymic stromal lymphopoietin (TSLP) were not detected. Several proinflammatory cytokines including TNFα and IL-12 were highly expressed in the AF from women who underwent preterm birth, whereas EGF was the highest in term birth samples. Exposure of esophageal epithelial cells to AF resulted in transient phosphorylation of ERK1/2 and the transcription of early response genes, highlighting the direct impact of AF on esophageal epithelial cells. In a three-dimensional spheroid model, AF modified the esophageal epithelial differentiation program and enhanced the transcription of IL-13-target genes, including <i>CCL26</i> and <i>CAPN14</i>, which encodes for a major genetic susceptibility locus for eosinophilic esophagitis. Notably, <i>CAPN14</i> exhibited upregulation in spheroids exposed to preterm but not term AF following differentiation. Collectively, our findings call attention to the role of AF as a potential mediator of the intrauterine environment that influences subsequent esophageal disorders.<b>NEW & NOTEWORTHY</b> The interaction between amniotic fluid and the esophageal epithelium during pregnancy modifies esophageal epithelial differentiation and subsequent responsiveness to inflammatory stimuli, including interleukin 13 (IL-13). This interaction may predispose individuals to inflammatory conditions of the esophagus, such as eosinophilic esophagitis (EoE), in later stages of life.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatostatin peptides prevent increased human colonic epithelial permeability induced by hypoxia.","authors":"Ibrahim Rajput, Vazhaikkurichi M Rajendran, Andrew J Nickerson, J Peter A Lodge, Geoffrey I Sandle","doi":"10.1152/ajpgi.00057.2024","DOIUrl":"10.1152/ajpgi.00057.2024","url":null,"abstract":"<p><p>Mesenteric ischemia increases gut permeability and bacterial translocation. In human colon, chemical hypoxia induced by 2,4-dinitrophenol (DNP) activates basolateral intermediate conductance K⁺ (IK) channels (designated KCa3.1 or KCNN4) and increases paracellular shunt conductance/permeability (<i>G</i>_S), but whether this leads to increased macromolecule permeability is unclear. Somatostatin (SOM) inhibits IK channels and prevents hypoxia-induced increases in <i>G</i>_S. Thus, we examined whether octreotide (OCT), a synthetic SOM analog, prevents hypoxia-induced increases <i>G</i>_S in human colon and hypoxia-induced increases in total epithelial conductance (<i>G</i>_T) and permeability to FITC-dextran 4000 (FITC) in rat colon. The effects of serosal SOM and OCT on increases in <i>G</i>_S induced by 100 µM DNP were compared in isolated human colon. The effects of OCT on DNP-induced increases in <i>G</i>_T and transepithelial FITC movement were evaluated in isolated rat distal colon. <i>G</i>_S in DNP-treated human colon was 52% greater than in controls (<i>P</i> = 0.003). <i>G</i>_S was similar when 2 µM SOM was added after or before DNP treatment, in both cases being less (<i>P</i> < 0.05) than with DNP alone. OCT (0.2 µM) was equally effective preventing hypoxia-induced increases in <i>G</i>_S, whether added after or before DNP treatment. In rat distal colon, DNP significantly increased <i>G</i>_T by 18% (<i>P</i> = 0.016) and mucosa-to-serosa FITC movement by 43% (<i>P</i> = 0.01), and 0.2 µM OCT pretreatment completely prevented these changes. We conclude that OCT prevents hypoxia-induced increases in paracellular/macromolecule permeability and speculate that it may limit ischemia-induced gut hyperpermeability during abdominal surgery, thereby reducing bacterial/bacterial toxin translocation and sepsis.<b>NEW & NOTEWORTHY</b> Somatostatin (SOM, 2 µM) and octreotide (OCT, 0.2 µM, a long-acting synthetic analog of SOM) were equally effective in preventing chemical hypoxia-induced increases in paracellular shunt permeability/conductance in isolated human colon. In rat distal colon, chemical hypoxia significantly increased total epithelial conductance and transepithelial movement of FITC-dextran 4000, changes completely prevented by 0.2 µM OCT. OCT may prevent or limit gut ischemia during abdominal surgery, thereby decreasing the risk of bacterial/bacterial toxin translocation and sepsis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional and conditional variability of FXR: new lessons on ileal inflammation and gut barrier functions.","authors":"Susan A Joyce, Dervla O'Malley","doi":"10.1152/ajpgi.00226.2024","DOIUrl":"10.1152/ajpgi.00226.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The keratin cytoskeleton emerges as a regulator of mitochondria in the colonic epithelium.","authors":"Michelle Dixit, Joseph Burclaff","doi":"10.1152/ajpgi.00228.2024","DOIUrl":"10.1152/ajpgi.00228.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise training ameliorates carbon tetrachloride-induced liver fibrosis and anxiety-like behaviors.","authors":"Yuki Tomiga, Kenichi Tanaka, Joji Kusuyama, Akiko Takano, Yasuki Higaki, Keizo Anzai, Hirokazu Takahashi","doi":"10.1152/ajpgi.00161.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00161.2024","url":null,"abstract":"<p><p>Chronic liver diseases and cirrhosis are associated with mood disorders. Regular exercise has various beneficial effects on multiple organs, including the liver and brain. However, the therapeutic effect of exercise on liver fibrosis concomitant with mood disorders, such as anxiety, has not been evaluated. In this study, the effects of exercise training on liver fibrosis-related anxiety-like behaviors were evaluated. Male C57/BL6 mice were divided into four groups: vehicle-sedentary, vehicle-exercise, carbon tetrachloride (CCl4)-sedentary, and CCl4-exercise. Liver fibrosis was induced by CCl4 administration for 8 weeks, exercise was applied in the form of voluntary wheel running. After intervention, anxiety-like behavior was assessed using the elevated plus maze. CCl4 increased liver and serum fibrotic markers, as measured by blood analysis, histochemistry, and qRT-PCR, and these changes were attenuated by exercise training. CCl4 induced anxiety-like behavior, which was ameliorated by exercise training. In the hippocampus, CCl4-induced changes in mRNA and protein levels of factors related to anxiety, including BDNF and nNOS, were reversed by exercise. These results suggested that hepatic fibrosis-related anxiety-like behaviors are induced by excess hippocampal nNOS, and the beneficial effects of exercise were mediated by increases in BDNF and reductions in nNOS. The percentage of fibrotic area was negatively correlated with anti-anxiety behavior and positively associated with hippocampal nNOS protein levels. Liver fibrosis-related anxiety-like behaviors could be alleviated through the regulation of hippocampal BDNF and nNOS via exercise training. These results support the therapeutic value of exercise by targeting the mechanisms underlying liver fibrosis and associated anxiety.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallbladder mucoceles in dogs: A novel form of acquired CFTR dysfunction causing localized cystic fibrosis-like disease.","authors":"David K Meyerholz, David A Stoltz","doi":"10.1152/ajpgi.00302.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00302.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}