Journal of Leukocyte Biology最新文献

{"title":"The relevance of eosinophils in chronic obstructive pulmonary disease: inflammation, microbiome, and clinical outcomes.","authors":"Andrew Higham, Augusta Beech, Dave Singh","doi":"10.1093/jleuko/qiae153","DOIUrl":"10.1093/jleuko/qiae153","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease is caused by the inhalation of noxious particles such as cigarette smoke. The pathophysiological features include airway inflammation, alveolar destruction, and poorly reversible airflow obstruction. A subgroup of patients with chronic obstructive pulmonary disease has higher blood eosinophil counts, associated with an increased response to inhaled corticosteroids and increased biomarkers of pulmonary type 2 inflammation. Emerging evidence shows that patients with chronic obstructive pulmonary disease with increased pulmonary eosinophil counts have an altered airway microbiome. Higher blood eosinophil counts are also associated with increased lung function decline, implicating type 2 inflammation in progressive pathophysiology in chronic obstructive pulmonary disease. We provide a narrative review of the role of eosinophils and type 2 inflammation in the pathophysiology of chronic obstructive pulmonary disease, encompassing the lung microbiome, pharmacological targeting of type 2 pathways in chronic obstructive pulmonary disease, and the clinical use of blood eosinophil count as a chronic obstructive pulmonary disease biomarker.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"927-946"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468632","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":"TIGIT stimulation suppresses autoimmune uveitis by inhibiting Th17 cell infiltration.","authors":"Kayleigh Peters, Trisha McDonald, Fauziyya Muhammad, Adrien Brady, John Dostal, Darren J Lee","doi":"10.1093/jleuko/qiae116","DOIUrl":"10.1093/jleuko/qiae116","url":null,"abstract":"<p><p>T cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint molecule that suppresses T cell activation and promotes an immunosuppressive environment to suppress autoimmune diseases. However, the impact of a TIGIT agonist as a treatment for ocular autoimmune disease has not been investigated. We examined TIGIT expression on T helper 17 (Th17) and regulatory T cells (Tregs), the role of TIGIT on experimental autoimmune uveitis and Th17 cells, and the impact of Treg generation following TIGIT stimulation. TIGIT stimulation at the onset of clinical symptoms reduced the severity of uveitis and suppressed infiltration of Th17 cells into the eye. Further, Tregs from mice treated with the TIGIT agonist were capable of suppressing experimental autoimmune uveitis in recipient mice. This report demonstrates that stimulation of TIGIT at onset of disease suppresses symptoms and allows for induction of regulatory immunity that provides resistance to uveitis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1054-1060"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086135","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":"The antitumor effect of extracellular vesicles derived from cytokine-activated CD8+ T cells.","authors":"Lin Zhang, Yuan Meng, Yang An, Xuena Yang, Feng Wei, Xiubao Ren","doi":"10.1093/jleuko/qiae117","DOIUrl":"10.1093/jleuko/qiae117","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are nano-sized membrane particles secreted by various cell types that are involved in many important cellular processes. Recently, EVs originating from immune cells, such as dendritic cells, chimeric antigen receptor T cells, and natural killer cells, have attracted much attention because of their known direct and indirect antitumor activity. Here, we report the EVs released by cytokine-activated CD8+ T (caCD8) cells and its cytotoxicity against cancer cells. CaCD8 cells can release EVs following stimulation of CD8+ T cells with an anti-CD3 antibody and a cytokine cocktail ex vivo. The isolated vesicles have typical EV characteristics, such as an oval shape and a size distribution between 30 and 200 nm, as well as CD81 expression. Notably, caCD8-EVs displayed cytotoxicity against various cancer cells in vitro. Furthermore, mechanism analysis demonstrates that caCD8-EVs not only contain typical cytotoxic proteins (i.e. granzyme B and perforin), but also significantly enrich interferon γ (IFNγ) compared with caCD8 cells. EV-derived IFNγ participates in EV-induced apoptosis in cancer cells. Therefore, our data reveal antitumor effects of EVs secreted from caCD8 cells and the potential role of the EV-derived IFNγ.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1033-1044"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957592","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":"G-CSF induces neutrophil extracellular traps formation and promotes ovarian cancer peritoneal dissemination.","authors":"Michiko Bun, Mahiru Kawano, Gaku Yamamoto, Mina Sakata, Kotaro Shimura, Aska Toda, Koji Nakamura, Yasuto Kinose, Michiko Kodama, Kae Hashimoto, Eiji Kobayashi, Kenjiro Sawada, Tadashi Kimura","doi":"10.1093/jleuko/qiae166","DOIUrl":"10.1093/jleuko/qiae166","url":null,"abstract":"<p><p>Epithelial ovarian cancer is characterized by aggressive peritoneal dissemination. Neutrophils are mobilized to peritoneal cavity in some patients with ovarian cancer dissemination; however, its pathological significance remains unknown. This study aimed to investigate the role of neutrophil extracellular traps (NETs) in ovarian cancer dissemination. We conducted a retrospective analysis of clinical data and samples from 340 patients with ovarian cancer who underwent primary surgery between 2007 and 2016 at the Osaka University Hospital. In vitro, NETs formation was induced by stimulating human peripheral neutrophils. The human ovarian cancer cell line, OVCAR8, was cocultured with NETs. For an ovarian cancer dissemination mouse model, we performed an intraperitoneal injection of OVCAR8 cells into nude mice. The association between NETs and peritoneal dissemination was explored, and model mice were treated with the PAD4 inhibitor GSK484 to assess antitumor efficacy. Neutrophilia (neutrophil count >7000/mm3) correlated with shorter survival, advanced peritoneal dissemination, elevated granulocyte colony-stimulating factor (G-CSF) levels, increased neutrophil count in ascites, and augmented NETs foci in peritoneal dissemination sites. In vitro assays revealed that G-CSF stimulated neutrophils to form NETs, promoting cancer cell adhesion. In vivo investigations revealed that G-CSF-producing tumor-bearing mice had accelerated peritoneal dissemination and poor prognosis. NETs formation was pathologically observed at the peritoneal dissemination sites. Inhibition of NETs formation by GSK484 significantly delayed peritoneal dissemination in vivo. In conclusion, G-CSF was associated with intra-abdominal NETs formation and increased peritoneal dissemination. NETs represent potential therapeutic targets for ovarian cancer, particularly in patients with neutrophilia.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1157-1168"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855693","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":"Hypereosinophilic syndrome response to mepolizumab in the setting of a compassionate use program.","authors":"Gauthier Coussement, Julien Catherine, Florence Roufosse","doi":"10.1093/jleuko/qiae152","DOIUrl":"10.1093/jleuko/qiae152","url":null,"abstract":"<p><p>Mepolizumab, an anti-interleukin-5 antibody, has been proven a safe and effective glucocorticoid (GC)-sparing drug for many patients with nonclonal hypereosinophilic syndrome (HES) and is now approved in many countries. It remains unclear, however, which patients are most likely to benefit from therapy and whether the currently approved dosing regimen is appropriate for all. This observational retrospective study included all patients with HES who were enrolled in the MHE104317 compassionate use program (CUP) in our center. Patient and disease characteristics, mepolizumab dosing, and both clinical and hematological responses to treatment were collected from medical files. Treatment responses and mepolizumab dosing requirements were analyzed according to disease characteristics. Eighteen patients with HES were enrolled in the CUP, of whom nine are still on treatment. The median duration of exposure to mepolizumab was 45 mo (maximum 18 yr). A lower number of affected organs, requirement for GC dosing ≤10 mg prednisone-equivalent, and single-organ HES were associated with a higher likelihood of complete response. Lymphocytic variant HES (L-HES) was less treatment-responsive, leading to withdrawal and/or requiring higher mepolizumab dosing to achieve some degree of disease control. In contrast, all patients with single-organ disease had a complete response that could often be maintained despite increasing between-dose intervals. Few potentially treatment-related adverse events were observed despite prolonged exposure. This study confirms the efficacy and safety of mepolizumab in HES, although patients with L-HES rarely experience a complete response. In contrast, patients with single-organ disease affecting the lungs are often super-responders, and decreasing mepolizumab dosing may be attempted.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1021-1032"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544925","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":"Treponema pallidum recombinant protein Tp0768 enhances the ability of HUVECs to promote neutrophil chemotaxis through the TLR2/ER stress signaling pathway.","authors":"Ting Cao, Yue Li, Xiangping Zhou, Yun Tang, Bisha He, Qian Cao, Yibao Hu, En Chen, Yumeng Li, Xiaoping Xie, Feijun Zhao, Xiaopeng Lan, Shuangquan Liu","doi":"10.1093/jleuko/qiae114","DOIUrl":"10.1093/jleuko/qiae114","url":null,"abstract":"<p><p>Neutrophils are essential cells involved in inflammation. However, the specific mechanism of neutrophil chemotaxis induced by Treponema pallidum remains unknown. In this study, human umbilical vein endothelial cells (HUVECs) were utilized as target cells to investigate the expression levels of chemokines when stimulated with different concentrations of Tp0768 (also known as TpN44.5 or TmpA, a T. pallidum infection dependent antigen). The results indicated that Tp0768 treatment enhanced neutrophil chemotaxis in HUVECs, which was closely associated with the expression levels of CXCL1, CXCL2, and CXCL8 (also known as interleukin-8). At the same time, the results show that the Toll-like receptor 2 (TLR2) signaling pathway is activated and that endoplasmic reticulum (ER) stress occurs. Furthermore, the findings revealed that the use of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and immunoglobulin-regulated enhancer 1 (IRE1) inhibitors reduced the expression levels of CXCL1, CXCL2, and CXCL8. Additionally, inhibiting TLR2 significantly decreased the expression levels of ER stress-related proteins (PERK and IRE1), CXCL1, CXCL2, and CXCL8. Consequently, neutrophil chemotaxis was significantly inhibited after treatment with TLR2, PERK, and IRE1 inhibitors. These findings shed light on the role of Tp0768 in enhancing neutrophil chemotaxis in endothelial cells, providing a foundation for further exploration of syphilis pathogenesis and offering a new direction for the diagnosis and treatment of T. pallidum infection.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1045-1053"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945199","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":"Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies.","authors":"Alissa Oakes, Yuchen Liu, Patrycja M Dubielecka","doi":"10.1093/jleuko/qiae130","DOIUrl":"10.1093/jleuko/qiae130","url":null,"abstract":"<p><p>The complement cascade is an ancient and highly conserved arm of the immune system. The accumulating evidence highlights elevated activity of the complement cascade in cancer microenvironment and emphasizes its effects on the immune, cancer, and cancer stroma cells, pointing to a role in inflammation-mediated etiology of neoplasms. The role the cascade plays in development, progression, and relapse of solid tumors is increasingly recognized, however its role in hematological malignancies, especially those of myeloid origin, has not been thoroughly assessed and remains obscure. As the role of inflammation and autoimmunity in development of myeloid malignancies is becoming recognized, in this review we focus on summarizing the links that have been identified so far for complement cascade involvement in the pathobiology of myeloid malignancies. Complement deficiencies are primary immunodeficiencies that cause an array of clinical outcomes including an increased risk of a range of infectious as well as local or systemic inflammatory and thrombotic conditions. Here, we discuss the impact that deficiencies in complement cascade initiators, mid- and terminal-components and inhibitors have on the biology of myeloid neoplasms. The emergent conclusions indicate that the links between complement cascade, inflammatory signaling, and the homeostasis of hematopoietic system exist, and efforts should continue to detail the mechanistic involvement of complement cascade in the development and progression of myeloid cancers.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"966-984"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246879","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":"Piezo1 restrains proinflammatory response but is essential in T cell-mediated immunopathology.","authors":"Sung Hee Choi, Alicia Santin, Jay T Myers, Byung-Gyu Kim, Saada Eid, Suzanne L Tomchuck, Daniel T Kingsley, Alex Y Huang","doi":"10.1093/jleuko/qiae242","DOIUrl":"https://doi.org/10.1093/jleuko/qiae242","url":null,"abstract":"<p><p>Piezo1 is a mechanosensitive, nonselective Ca2+ channel which is broadly expressed in CD4+ T cells. Using lineage-specific Piezo1 knockout mice (Piezo1cKO), we show that loss of Piezo1 in CD4+ T cells significantly increased IFNγ and IL-17 production in vitro under TH1 and TH17 polarizing conditions, respectively. Despite their intrinsic proinflammatory phenotype, Piezo1cKO T cells are incapable of establishing disease in vivo in three separate adoptive transfer (AT) T cell-mediated inflammatory mouse models, including experimental autoimmune encephalomyelitis, inflammatory bowel disease (IBD), and graft versus-host disease. These phenomena coincided with a decreased effector memory (CD44hiCD62Llo) CD4+ T cell pool derived from donor Piezo1cKO T cells, an observation that is related to intrinsic T-cell fitness, as co-transfer IBD mouse model revealed a deficiency in the CD4+ effector memory population derived only from the naïve Piezo1cKO but not co-infused Piezo1WT CD4+ T cell source. Taken together, our results support Piezo1 as restraining proinflammatory T cell differentiation while contributing to the generation and persistence of the effector memory pool during CD4+ T cell-mediated immunopathology.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568705","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":"Carboxylesterase 1 directs the metabolic profile of dendritic cells to a reduced inflammatory phenotype.","authors":"Ahmed M I Elfiky, Jessica López Canñizares, Jiarong Li, Andrew Y F Li Yim, Arthur J Verhoeven, Mohammed Ghiboub, Wouter J de Jonge","doi":"10.1093/jleuko/qiae137","DOIUrl":"10.1093/jleuko/qiae137","url":null,"abstract":"<p><p>The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. The carboxylesterase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells; however, its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DC differentiation in inflammatory models. CES1 expression was analyzed during CD14+ monocytes differentiation to DCs (MoDCs) using quantitative polymerase chain reaction. A CES1 inhibitor (WWL113) was applied during MoDC differentiation. Surface markers, secreted cytokines, lactic acid production, and phagocytic and T cell polarization capacity were analyzed. The transcriptomic and metabolic profiles were assessed with RNA sequencing and mass spectrometry, respectively. Cellular respiration was assessed using seahorse respirometry. Transgenic mice were used to assess the effect of CES1 overexpression in DCs in inflammatory models. CES1 expression peaked early during MoDC differentiation. Pharmacological inhibition of CES1 led to higher expression of CD209, CD86 and MHCII. WWL113 treated MoDCs secreted higher quantities of interleukin (IL)-6, IL-8, tumor necrosis factor, and IL-10 and demonstrated stronger phagocytic ability and a higher capacity to polarize T helper 17 differentiation in an autologous DC-T cell coculture model. Transcriptomic profiling revealed enrichment of multiple inflammatory and metabolic pathways. Functional metabolic analysis showed impaired maximal mitochondrial respiration capacity, increased lactate production, and decreased intracellular amino acids and tricarboxylic acid cycle intermediates. Transgenic human CES1 overexpression in murine DCs generated a less inflammatory phenotype and increased resistance to T cell-mediated colitis. In conclusion, CES1 inhibition directs DC differentiation toward a more inflammatory phenotype that shows a stronger phagocytic capacity and supports T helper 17 skewing. This is associated with a disrupted mitochondrial respiration and amino acid depletion.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1094-1108"},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310904","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":"Resveratrol Potentiates BCG-induced Trained Immunity in Human Monocytes.","authors":"Ozlem Bulut, Ilayda Baydemir, Gizem Kilic, Jorge Domínguez-Andrés, Mihai G Netea","doi":"10.1093/jleuko/qiae241","DOIUrl":"https://doi.org/10.1093/jleuko/qiae241","url":null,"abstract":"<p><p>Resveratrol is a natural polyphenol derived from plants such as grapes and berries. In addition to its role in plants during injury and infection, various cardioprotective, neuroprotective, and longevity-promoting effects were reported in diverse model organisms. The primary target of resveratrol is the deacetylase Sirtuin 1 (SIRT1), which regulates many immunological processes, including BCG-induced trained immunity response in humans. We, therefore, investigated the effect of resveratrol on trained immunity induced by BCG, β-glucan, C. albicans, or oxidized low-density lipoprotein (oxLDL). Using an in-vitro model of trained immunity with monocytes obtained from healthy donors, we demonstrate that resveratrol amplifies BCG-induced trained immunity regarding IL-6 and TNFα production after a secondary challenge. Although resveratrol did not improve and even limited glycolysis, oxidative phosphorylation, and reactive oxygen species production, it enhanced the permissive epigenetic mark H3K27Ac on IL-6 and TNFα promoters. In contrast to BCG-induced trained immunity, resveratrol potently inhibited training induced by β-glucan, C. albicans, oxLDL, and muramyl dipeptide (MDP), a peptidoglycan component of BCG. Resveratrol's unique boosting effect on BCG training depended on BCG being alive and metabolically active. These results suggest that resveratrol might amplify the effects of BCG vaccination, which should be mechanistically characterized further. In addition, resveratrol could alleviate oxLDL-induced training of innate immune cells in atherosclerosis, and in-vivo studies of trained immunity combined with resveratrol are warranted to explore these therapeutic possibilities.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568802","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}