Journal of Leukocyte Biology最新文献

{"title":"Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis.","authors":"Tarun Barbhuyan, Rakesh B Patel, Ivan Budnik, Anil K Chauhan","doi":"10.1093/jleuko/qiae161","DOIUrl":"10.1093/jleuko/qiae161","url":null,"abstract":"<p><p>Integrin α9β1 is known to stabilize leukocyte adhesion to the activated endothelium. We determined the role of myeloid cell α9β1 in early atherosclerosis in two models: α9Mye-KOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat \"Western\" diet for 4 wk. α9Mye-KOApoe-/- mice exhibited reduced early lesions in the aortae and aortic sinuses (P < 0.05 vs α9WT Apoe-/- mice). Similar results were obtained in α9Mye-KO BM→Ldlr-/- mice (P < 0.05 vs α9WT BM→Ldlr-/- mice). Reduced early atherosclerosis in α9Mye-KOApoe-/- mice was associated with decreased neutrophil and neutrophil extracellular traps (NETs) content in the aortic lesions (P < 0.05 vs α9WTApoe-/-). Vascular cell adhesion molecule-1-stimulated neutrophils from α9Mye-KO mice exhibited reduced adhesion, transmigration, and NETs formation (NETosis) (P < 0.05 vs α9WT neutrophils). Reduced NETosis was associated with decreased extracellular signal-regulated kinase phosphorylation, peptidyl arginine deiminase 4, and citrullinated histone H3 expression. In summary, genetic ablation of myeloid cell-specific α9 reduces early atherosclerosis, most likely by reducing neutrophil adhesion, transmigration, and NETosis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1208-1214"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Removal of circulating mitochondrial N-formyl peptides via immobilized antibody therapy restores sepsis-induced neutrophil dysfunction.","authors":"Woon Yong Kwon, Yoon Sun Jung, Gil Joon Suh, Sung Hee Kim, Areum Lee, Jeong Yeon Kim, Hayoung Kim, Heesu Park, Jieun Shin, Taegyun Kim, Kyung Su Kim, Kiyoshi Itagaki, Carl J Hauser","doi":"10.1093/jleuko/qiae169","DOIUrl":"10.1093/jleuko/qiae169","url":null,"abstract":"<p><p>During recovery from septic shock, circulating mitochondrial N-formyl peptides predispose to secondary infection by occupying formyl peptide receptor 1 on the neutrophil (polymorphonuclear leukocyte) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mitochondrial N-formyl peptides in clinical settings. Thus, we studied how to remove mitochondrial N-formyl peptides from septic-shock plasma and whether such removal could preserve cell-surface formyl peptide receptor 1 and restore sepsis-induced polymorphonuclear leukocyte dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mitochondrial N-formyl peptide removal rescued polymorphonuclear leukocyte formyl peptide receptor 1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mitochondrial N-formyl peptide exposure. However, polymorphonuclear leukocyte functional recovery occurred in a stepwise fashion over 30 to 90 min. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model, systems using blood samples obtained from patients with septic shock, antimitochondrial N-formyl peptide antibodies alone failed to eliminate mitochondrial N-formyl peptides from septic-shock plasma or inhibit mitochondrial N-formyl peptide activity. We therefore created a beads-based antimitochondrial N-formyl peptide antibody cocktail by combining protein A/sepharose with antibodies specific for the most potent human mitochondrial N-formyl peptide chemoattractants. The beads-based antimitochondrial N-formyl peptide antibody cocktail treatment successfully removed those active mitochondrial N-formyl peptides from septic-shock plasma. Furthermore, the beads-based antimitochondrial N-formyl peptide antibody cocktail treatment significantly restored chemotactic and bactericidal dysfunction of polymorphonuclear leukocytes obtained from patients with septic shock who developed secondary infections. By clearing circulating mitochondrial N-formyl peptides, the immobilized antimitochondrial N-formyl peptide antibody therapy prevented mitochondrial N-formyl peptide interactions with surface formyl peptide receptor 1, thereby restoring [Ca2+]i-dependent polymorphonuclear leukocyte antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1169-1183"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897572","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":"Combination therapy with immune agonists and senescence-inducing agents delivers promise for immunotherapeutic success in pancreatic cancer.","authors":"Renee R Anderko, Amer H Zureikat, Tullia C Bruno","doi":"10.1093/jleuko/qiae234","DOIUrl":"https://doi.org/10.1093/jleuko/qiae234","url":null,"abstract":"","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545881","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":"Neutrophil Extracellular Traps: Potential Thrombotic Markers and Therapeutic Targets in Colorectal Cancer.","authors":"Xianye Huang, Rongquan He, Yanfeng Jiang, Jing Tang, Xiaoyu Xu, Shixue Laoguo, Gang Chen, Jie Ma","doi":"10.1093/jleuko/qiae235","DOIUrl":"https://doi.org/10.1093/jleuko/qiae235","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are promising promoters in venous thromboembolism (VTE). In the present study, we have investigated the potential thrombogenic role of NETs in colorectal cancer (CRC). A total of 583 patients with gastrointestinal malignancies who were diagnosed with or without VTE by extremities arteriovenous ultrasound and computed tomography were enrolled. The incidence of VTE in CRC was as high as 17.53%. In serological ELISA experiments, Cit-H3, MPO and cfDNA were significantly overexpressed in CRC patients with VTE compared to CRC patients without VTE and healthy individuals. Neutrophils from CRC patients with VTE produced appreciable amounts of NETs after stimulation with phorbol-12-myristate-13-acetate, which were lacking in CRC patients without VTE and healthy individuals. CfDNA was positively correlated with plasmin-α2-antiplasmin complex and tissue plasmin activator inhibitor-1 complex, and Cit-H3 was positively correlated with plasmin-α2-antiplasmin complex, suggesting that NETs are associated with increased fibrinolytic activity. We screened some NETs-related genes by analysing several high-throughput sequencing datasets of VTE and NETs. FCGR1A was identified as the optimal target gene by pan-cancer expression analysis and survival analysis. FCGR1A was significantly overexpressed in the peripheral blood of CRC patients without VTE compared to healthy individuals and showed a positive correlation with cfDNA. Neutrophil-derived NETs were significantly reduced by FCGR1A inhibitor exposure. These findings indicate that NETs are actively involved in VTE in CRC. NETs are promising thrombotic marker and therapeutic target in CRC to prevent the thrombotic consequences of cancer.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502162","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":"CD56 does not contribute to the anti-tumor, tissue homing, and glycolytic capacity of human NK cells.","authors":"Ana L Portillo, Eduardo A Rojas, Misaal Mehboob, Adnan Moinuddin, Elizabeth Balint, Emily Feng, Christopher Silvestri, Fatemeh Vahedi, Tyrah M Ritchie, Alexa J Mansour, Jonathan L Bramson, Ali A Ashkar","doi":"10.1093/jleuko/qiae227","DOIUrl":"https://doi.org/10.1093/jleuko/qiae227","url":null,"abstract":"<p><p>Natural Killer (NK) cells are critical innate immune cells involved in the clearance of virally infected and malignant cells. Human NK cells are distinguished by their surface expression of CD56 and a lack of CD3. While CD56 expression and cell surface density has long been used as the prototypic marker to characterize primary human NK cell functional subsets, the exact functional role of CD56 in primary human NK cells is still not fully understood. Here we eliminated the expression of CD56 in human ex vivo expanded NK cells (CD56bright) using CRISPR/Cas9 in order to assess the function of CD56 in this highly activated and cytotoxic NK cell population. We show that the expression of CD56 has no effect on NK cell proliferative capacity or expression of various activation and inhibitory markers. Further, CD56 does not contribute to NK cell-mediated cytotoxicity, inflammatory cytokine production, or the ability of NK cells to control tumor engraftment in vivo. We also found that while deletion of CD56 did not impact NK cell glycolytic metabolism it did increase NK cell reliance on oxidative phosphorylation. Lastly, CD56 does not alter expanded NK cell in vivo tissue trafficking. Our results indicate that while CD56 expression could be used to indicate a hyper-functional state of NK cells, it does not directly influence the anti-tumor functions of expanded NK cells.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502158","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":"Reversible role of MIR654/3P and MIR9/3P in pathogenesis of Epstein-Barr Virus negative, but not positive, Burkitt's lymphoma.","authors":"Yu Gong, Wenhua Fu","doi":"10.1093/jleuko/qiae237","DOIUrl":"https://doi.org/10.1093/jleuko/qiae237","url":null,"abstract":"<p><p>The role of MIR654 in Burkitt's lymphoma (BL) and whether it impacts expression of MYC, and its downstream activated MIR9 is not known. Expression of MYC, MYCN, MYCL, MIR9/3P, MIR654/5P, and MIR654/3P were assessed by qRT-PCR in biopsy samples from Epstein-Barr virus (EBV)- and EBV+ BL patients and BL cell lines. Effects of modulation of MIR9/3P and MIR654/3P on cell proliferation, apoptosis and chemosensitivity were evaluated. Luciferase reporter assay was performed to validate putative target of MIR654/5P. Effects of MIR9/3P and MIR654/3P on tumor burden and disease outcome were evaluated using xenograft model of BL. Expression of MYC, MYCN, and MIR9/3P was higher in all BL patient samples and cell lines. Expression of MIR654/3P was downregulated in EBV- BL patient samples and cell lines compared to either noncancer lymphoid reactive hyperplasia (LRH) or EBV+ samples and cell lines. Additionally, MIR654/3P overexpression inhibited cell proliferation, induced apoptosis, and increased chemosensitivity in EBV- BL cell lines. Luciferase reporter assay confirmed that MYC is a target of MIR654/3P in both EBV- and EBV+ BL cell lines; however, the effect of MIR654/3P-mediated targeting of MYC is overridden in EBV+ cells. Administration of MIR654/3P mimic or MIR9/3P antagomir in the xenograft model decreased tumor burden and increased survival. Combined intervention with MIR654/3P mimic and MIR9/3P antagomir had synergistic action on decreasing tumor burden and improving disease outcome. MIR654/3P, as a putative tumor suppressor in EBV- BL, collaborated MIR9/3P might serve as a therapeutic agent to treat EBV- BL patients in combination with existing chemotherapy and immunotherapy regimes.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502163","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":"Characteristics of the IgM Repertoires in the Peripheral Blood of Early Rheumatoid Arthritis Patients.","authors":"Binbin Hong, Qiulan Li, Qiaoling Liu, Rongfu Huang, Mei'er Wang, Ziyue Guo, Jiewei Huang, Jiaqi Wang, Chunmei Fan, Tianlei Ying","doi":"10.1093/jleuko/qiae236","DOIUrl":"https://doi.org/10.1093/jleuko/qiae236","url":null,"abstract":"<p><p>Rheumatoid arthritis is a common autoimmune disease, but little is known about the characteristics of the B cell repertoires in the peripheral blood. In this study, the peripheral IgM repertoires of early rheumatoid arthritis (ERA) patients were analyzed by high-throughput sequencing and bioinformatics analyses. Clonal expansion was observed in IgM repertoires of ERA patients. Interestingly, a subset of the dominant clones in ERA repertoires showed self- and poly-reactivity to several autoantigens. The clones were also present in IgM repertoires of healthy adults but they were not expanded, suggesting that may stem from the natural auto-reactive B cell repertoire. Additionally, the ERA repertoires exhibited a greater extent of somatic hypermutations, particularly in the ERA dominant clones, resulting in an enrichment of amino acids important for antigen-antibody interaction. The in-depth analysis of B-cell repertoires improved our knowledge of the IgM repertoires in early rheumatoid arthritis, offering potential insights into the disease's pathogenesis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502159","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":"Eosinophil-Airway Epithelial Cells crosstalk reveals the eosinophils-mediated DUOX1 up-regulation in a murine allergic inflammation setting.","authors":"Carla Raggi, Francesca Spadaro, Fabrizio Mattei, Adriana Rosa Gambardella, Francesco Noto, Sara Andreone, Michele Signore, Giovanna Schiavoni, Isabella Parolini, Claudia Afferni","doi":"10.1093/jleuko/qiae232","DOIUrl":"https://doi.org/10.1093/jleuko/qiae232","url":null,"abstract":"<p><p>Blood and airway eosinophilia represent markers for the endotype-driven treatment of allergic asthma. Little is known on mechanisms that link eosinophils and airway epithelial cells before and after these cells are infiltrated by eosinophils during allergic response. Given that innate immune mechanisms, mainly mediated by epithelial-derived cytokines (IL-33, IL-25, TSLP), induce eosinophil-maturing/attractive substances, we thought to evaluate the crosstalk between eosinophils and airway epithelial cells in the context of IL-33-mediated allergic inflammation. DUOX1 was previously described in clinically relevant aspects of allergic inflammation in a HDM -induced allergic asthma mice model, and in patients with chronic sinusitis or allergic asthma. Thus, we evaluated the involvement of HDM and eosinophils in the regulation of DUOX1 in airway epithelial cells. To recapitulate the lung environment present at the allergen challenge time in acute asthma, we set up an in vitro model based on murine bone marrow-derived eosinophils differentiated with IL-5 and then activated with IL-33 (EOs33) and TC1 or C57 airway epithelial cells. We found that treatment of epithelial cells with HDM induced an eosinophil-attractive environment and increased DUOX1 expression. Importantly, we found that the co-culture of airway epithelial cells with EOs33 or with conditioned medium from EOs33 enhanced the expression of DUOX1, which was further increased by combined stimulation (HDM plus EOs33). Our results suggest that lung recruited EOs once activated by IL-33 could be involved in a crosstalk loop with airway epithelial cells by DUOX1-mediated IL-33 secretion.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502161","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":"Distinct deregulation trends of transcriptional protein complexes in aging naive T cells.","authors":"Emel Kökrek, Pınar Pir","doi":"10.1093/jleuko/qiae231","DOIUrl":"https://doi.org/10.1093/jleuko/qiae231","url":null,"abstract":"<p><p>The impact of aging on T cell subsets, specifically CD4+ and CD8+ T cells, leading to immune system dysfunction, has been the focus of scientific investigation due to its potential to reverse age-associated deterioration. Transcriptomic and epigenomic studies have identified the primary regulators in T cell aging. However, comprehending the underlying dynamic mechanisms requires studying these proteins with their interactors. Here, we integrated single-cell RNA sequencing data of naive CD4+ and CD8+ T cells obtained from three different age groups with protein-protein and domain-domain interaction networks to predict and compare the transcriptional protein complexes and identify their capacity to explain age-associated variances. Our novel approach revealed significant effects of aging on the repertoire of complexes, which remains unchanged in naive CD4+ T cells, while in naive CD8+ T cells, it diminishes. In both cell types, there was major deregulation of complexes with the same composition, involving a range of transcription factors. This aging-associated deregulation is characterized by a specific set of protein complexes in naive CD4+ T cells, but this pattern is not observed in naive CD8+ T cells. SMAD3 and BCL11A complexes emerge as key markers in defining a trajectory in aging naive CD4+ T cells. These complexes can accurately distinguish between three different age groups, indicating their potential as targets. The direct link between SMAD3 and FOS complexes whose regulatory role has been previously implicated in aging and MBD3 as the novel key link between SMAD3 and BCL11A complexes implicate a coordinated mechanism in age-associated deregulation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502160","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":"Basophils Induce Pro-Tumorigenic Cytokines from A549 Lung Adenocarcinoma via Mechanisms Requiring IgE, Galectin-3, and IL-3 Priming.","authors":"John T Schroeder, Laurent Ehrlich, Anja P Bieneman","doi":"10.1093/jleuko/qiae233","DOIUrl":"https://doi.org/10.1093/jleuko/qiae233","url":null,"abstract":"<p><p>Galectin-3 (Gal-3) is implicated in innate immune cell activation in a host of diseases/conditions. We identified a unique response whereby human basophils secrete IL-4/IL-13 when co-cultured with A549 cells -a lung adenocarcinoma. While displaying parameters consistent with standard IgE-dependent activation, these Galectin-3-dependent responses occurred in the absence of specific IgE/allergen and required cell-to-cell contact. We now hypothesize that this mode of activation also impacts A549 function. Our findings show that cytokines are induced in basophil/A549 co-cultures that are not detected when either cell is cultured alone, in particular IL-6. As previously shown for IL-4/IL-13, IL-6 production also required cell-to-cell contact and was dependent on A549-Gal-3, since clones deficient of this lectin induced less cytokine. Using culture-derived basophils (CDBA), we demonstrate that the IL-6 response, and production of another tumorigenic factor, VEGF-A, are induced in CDBA/A549 co-cultures but only after passively sensitizing CDBA with IgE, in a manner similar to IL-4/IL-13. However, IgE-dependent activation of basophils/CDBA cultured alone failed to induce IL-6/VEGF. Importantly, IL-3-primed basophils, even those fixed with paraformaldehyde, readily induced IL-6/VEGF-A in co-cultures, thus verifying these cytokines are derived from A549. Overall, these results suggest a complex mechanism whereby Gal-3/IgE interactions between IL-3-primed basophils and A549 have the potential to modulate cytokine production by both cells. With Gal-3 implicated in many diseases ranging from asthma to cancer, but also in normal physiological conditions, such as wound healing, these findings are predicted to provide insight into the molecular mechanisms by which this lectin (and IgE) functions in these processes.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467619","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}