Immunologic Research最新文献

{"title":"A novel MALT1 variant in an Egyptian patient presenting with exfoliative dermatitis: a case-based review.","authors":"Rabab El Hawary, Safa Meshaal, Sohilla Lotfy, Dalia Abd Elaziz, Alia S Eldash, Aya Erfan, Radwa Alkady, Rania Darwish, Mai Saad, Engy Chohayeb, Nermeen Galal, Aisha M Elmarsafy","doi":"10.1007/s12026-024-09517-1","DOIUrl":"10.1007/s12026-024-09517-1","url":null,"abstract":"<p><p>Inborn errors of the CARD11-BCL10-MALT1 (CBM) signalosome have recently been shown to underlie severe combined immunodeficiency (SCID) and combined immunodeficiency (CID) with variable immunological and clinical phenotypes, and patients usually present with recurrent bacterial, viral, and fungal infections, periodontal disease, enteropathy, dermatitis, and failure to thrive. In the present study, we describe the clinical and immunological characteristics of an Egyptian patient with a mutation in the MALT1 gene. The patient suffered from an itchy exfoliative skin rash and eczematous lesions over his face and flexural surface of the limbs. He also had dental enamel erosion, repeated attacks of diarrhea, and pneumonia. He had elevated serum IgE and normal B- and T-lymphocyte subset counts, but there was an arrest in the B-cell maturation. DOCK8 expression on the lymphocytes by flow cytometry was normal. Next-generation sequencing revealed a novel homozygous variant in the MALT1 gene (c.762dup in exon 5 of 17; p.Ile255TyrfsTer10); this variant is likely pathogenic, thus supporting the genetic diagnosis of immunodeficiency-12 (IMD12). Although the presence of eczema, recurrent sinopulmonary, and staphylococcal infections are suggestive of DOCK8 deficiency, they are also a finding in CARD11 and MALT1 deficiency. Thus, whenever DOCK 8 has been excluded, the molecular diagnosis is mandatory as this could lead to discovering more patients hence better understanding and reporting of the phenotype and natural history of the disease especially since there are very few documented cases. Early diagnosis will also enable the proper patient management by hematopoietic stem cell transplantation (HSCT) prior to the establishment of infections and pulmonary damage leading to a better outcome.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender disparities in Behçet's syndrome: identifying distinct phenotypes through cluster analysis.","authors":"Gamze Kılıç, Kemal Faruk Körüklü, Muhammed Galip Kumcu, Elif Çakır, Murat Karkucak, Erkan Kılıç","doi":"10.1007/s12026-024-09498-1","DOIUrl":"10.1007/s12026-024-09498-1","url":null,"abstract":"<p><p>Behçet's syndrome (BS) is a complex, multi-systemic disorder with a global occurrence, notably concentrated along the Silk Road. This study aimed to investigate gender-specific expressions and clinical phenotypes in BS patients within the Eastern Black Sea Region of Turkey. A total of 290 BS patients were retrospectively analyzed between January 2013 and December 2023. Demographic characteristics, clinical manifestations, medical treatment, and pathergy test results were obtained from a review of medical records. The mean age was 45.79 ± 13.05, with a male-to-female ratio of 48.6:51.4. Male patients had higher papulopustular lesions (p < 0.001) and ocular involvement (p = 0.036), while females showed more frequent genital ulcers (p = 0.032). Medication usage showed gender-based variations, notably higher corticosteroid, azathioprine, and tumor necrosis factor-alpha inhibitor (TNFi) use in males (p < 0.001). Cluster analysis revealed five distinct clusters, each with unique features and gender predominance. Cardiovascular type, ocular type, and skin type predominantly featured male patients, while joint involvement type and neurologic and mucosal involvement type were more prevalent among female patients with BS. This research contributes valuable insights into the gender-related clinical variations of BS within a specific geographic region, fostering a more comprehensive understanding of this challenging syndrome. The identification of distinct clinical phenotypes facilitates the development of tailored treatment strategies, potentially leading to improved outcomes for patients with BS.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Inhibition of cIAP1/2 reduces RIPK1 phosphorylation in pulmonary endothelial cells and alleviate sepsis-induced lung injury and inflammatory response.","authors":"Xiaoyu Liu, Yan Li, Weijian Zhang, Nan Gao, Jie Chen, Cheng Xiao, Guoqiang Zhang","doi":"10.1007/s12026-024-09502-8","DOIUrl":"10.1007/s12026-024-09502-8","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA demethylase Tet2 promotes the terminal maturation of natural killer cells.","authors":"Yuqing Lin, Biyun Yang, Hailin Liu, Guanghe Ran, Liang Song, Meng Meng, Xiaofeng Yin, Qinghua Bi, Dongmei Yan, Youcai Deng, Yonghui Lu","doi":"10.1007/s12026-024-09506-4","DOIUrl":"10.1007/s12026-024-09506-4","url":null,"abstract":"<p><p>The cytotoxicity feature to eliminate malignant cells makes natural killer (NK) cells a candidate for tumor immunotherapy. However, this scenario is currently hampered by inadequate understanding of the regulatory mechanisms of NK cell development. Ten-Eleven-Translocation 2 (Tet2) is a demethylase whose mutation was recently shown to cause phenotypic defects in NK cells. However, the role of Tet2 in the development and maturation of NK cells is not entirely clear. Here we studied the modulatory role of Tet2 in NK cell development and maturation by generating hematopoietic Tet2 knockout mice and mice with Tet2 conditional deletion in NKp46⁺ NK cells. The results showed that both hematopoietic and NK cell conditional deletion of Tet2 had no effect on the early steps of NK cell development, but impaired the terminal maturation of NK cells defined by CD11b, CD43, and KLRG1 expression. In the liver, Tet2 deletion not only prevented the terminal maturation of NK cells, but also increased the proportion of type 1 innate lymphoid cells (ILC1s) and reduced the proportion of conventional NK cells (cNK). Moreover, hematopoietic deletion of Tet2 lowered the protein levels of perforin in NK cells. Furthermore, hematopoietic deletion of Tet2 downregulated the protein levels of Eomesodermin (Eomes), but not T-bet, in NK cells. In conclusion, our results demonstrate that Tet2 plays an important role in the terminal maturation of NK cells, and the Eomes transcription factor may be involved.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elastin-derived peptides (EDPs) as a potential pro-malignancy factor in human leukemia cell lines.","authors":"Konrad A Szychowski, Bartosz Skóra","doi":"10.1007/s12026-024-09511-7","DOIUrl":"10.1007/s12026-024-09511-7","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is currently considered to be an important factor influencing the migration and progression of cancer cells. Therefore, the aim of our study was to investigate the mechanism of action of elastin-derived peptides in cancerous cells derived from the immunological system, i.e., HL-60, K562, and MEG-A2 cell lines. Moreover, an attempt to clarify the involvement of c-SRC kinase in EDP mechanism of action was also undertaken. Our data show that the VGVAPG and VVGPGA peptides are not toxic in the studied cell lines. Moreover, due to the involvement of KI67 and PCNA proteins in the cell cycle and proliferation, we can assume that neither peptide stimulates cell proliferation. Our data suggest that both peptides could initiate the differentiation process in all the studied cell lines. However, due to the different origins (HL-60 and K562-leukemic cell line vs. MEG-A2-megakaryoblastic origin) of the cell lines, the mechanism may differ. The increase in the ELANE mRNA expression noted in our experiments may also suggest enhancement of the migration of the tested cells. However, more research is needed to fully explain the mechanism of action of the VGVAPG and VVGPGA peptides in the HL-60, K562, and MEG-A2 cell lines. HIGHLIGHTS: • VGVAPG and VVGPGA peptides do not affect the metabolic activity of HL-60, K562, and MEG-A2 cells. • mTOR and PPARγ proteins are involved in the mechanism of action of VGVAPG and VVGPGA peptides. • Both peptides may initiate differentiation in HL-60, K562, and MEG-A2 cell lines.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of HLA-G 3'UTR polymorphisms with hepatitis B virus infection in Tunisian population.","authors":"Ahmed Baligh Laaribi, Asma Mehri, Hamza Ben Yahia, Houda Chaouch, Wafa Babay, Amel Letaief, Hadda-Imene Ouzari, Naila Hannachi, Jalel Boukadida, Ines Zidi","doi":"10.1007/s12026-024-09516-2","DOIUrl":"10.1007/s12026-024-09516-2","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) infection is a major public health burden. The mechanisms of immune evasion during chronic HBV (CHB) infection are poorly understood. Human leukocyte antigen (HLA)-G, an immune checkpoint molecule, plays a crucial role in the tolerance mechanisms of various infectious diseases. The 3' untranslated region (3'UTR), including the HLA-G + 3142 C > G polymorphism (rs1063320) and the 14-pb Ins/Del (rs66554220) has been strongly suggested to influence HLA-G expression. This study conducted a case-control analysis to evaluate the potential correlation between the HLA-G + 3142 C > G polymorphism and HBV infection outcome in a Tunisian cohort. The HLA-G + 3142 C > G polymorphism was analysed by PCR-RFLP in 242 patients with chronic HBV infection (116 males and 126 females), 241 healthy controls (116 males and 125 females), and 100 spontaneously resolved subjects (52 males and 48 females). Patients with chronic HBV infection showed a higher frequency of the + 3142G allele compared to healthy controls and spontaneously resolved subjects (p = 0.001 and p = 0.002, respectively). An association between the + 3142G allele and high HBV DNA levels was observed when HBV patients were stratified based on their HBV DNA levels (p = 0.016). Furthermore, the dominant model (GG + GC vs CC) was associated with liver function parameters, including AST, ALT, and high HBV DNA levels (p = 0.04, p < 0.001 and p = 0.002, respectively). However, there was no significant association found between this polymorphism and the fibrosis stage (p = 0.32). The haplotype analysis, using a subset of previously published data on the HLA-G 14-pb Ins/Del polymorphism, revealed an association between the Ins/G haplotype and chronic HBV infection (H1: InsG, p < 0.001). Our findings suggest that the + 3142G allele is a risk factor for the persistence and progression of HBV infection, while the + 3142C allele serves as a protective allele associated with the spontaneous resolution of the infection. Additionally, the HLA-G 3'UTR haplotype Ins/G is associated with chronic HBV infection in the Tunisian population.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCR2+TREM-1+ monocytes promote natural killer T cell dysfunction contributing towards HBV disease progression.","authors":"Xiaojuan Wu, Wenling Zhao, Qiang Miao, Shiya Shi, Bin Wei, Limei Luo, Bei Cai","doi":"10.1007/s12026-024-09495-4","DOIUrl":"10.1007/s12026-024-09495-4","url":null,"abstract":"<p><p>Natural killer T (NKT) cells are amongst the most important innate immune cells against hepatitis B virus (HBV) infection. Moreover, previous studies have shown that HBV infection induced TREM-1+ expression in monocyte and secretion of inflammatory cytokines. Thus, this prompted us to elucidate the role of TREM-1+ monocytes in regulating the function of iNKT cells. Ninety patients and 20 healthy participants were enrolled in the study. The percentage and phenotype of iNKT cells and TREM-1+ monocytes were measured in the peripheral blood of healthy controls (HC), patients with chronic HBV infection (CHB), HBV-related liver cirrhosis (LC), and HBV-related acute-on-chronic liver failure (ACLF) via flow cytometry. Moreover, co-culture experiments with iNKT cells and TREM-1 overexpressing THP-1 cells were performed to determine the role of TREM-1 in the regulation of NKT cell function. We observed that the percentage of iNKT cells and CD4-iNKT cells gradually decreased, whereas the percentage of CCR2+TREM-1+ monocytes increased with the progression of the disease. In addition, activation of the TREM-1 signaling pathway induced the secretion of inflammatory cytokines leading to pyroptosis of iNKT cells and secretion of IL-17 contributing towards disease progression. Therefore, this study suggests that blocking the activation of TREM-1 in monocytes could promote the elimination of HBV by inhibiting pyroptosis of iNKT cells and restoring their function. However, further studies are required to validate these results that would help in developing new treatment strategies for patients with HBV infections.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of single-cell and bulk RNA sequencing revealed immune heterogeneity and its association with disease activity in rheumatoid arthritis patients.","authors":"Xiaofan Mao, Maohua Shi, Beiying Zhang, Rongdang Fu, Mengyun Cai, Sifei Yu, Kairong Lin, Chuling Zhang, Dingru Li, Guoqiang Chen, Wei Luo","doi":"10.1007/s12026-024-09513-5","DOIUrl":"10.1007/s12026-024-09513-5","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease characterized by cartilage, bone damage, synovial inflammation, hyperplasia, autoantibody production, and systemic features. To obtain an overall profile of the immune environment in RA patients and its association with clinical features, we performed single-cell transcriptome and T-cell receptor sequencing of mononuclear cells from peripheral blood (PBMC) and synovial fluid (SF) from RA patients, integrated with two large cohorts with bulk RNA sequencing for further validation and investigation. Dendritic cells (DCs) exhibited relatively high functional heterogeneity and tissue specificity in relation to both antigen presentation and proinflammatory functions. Peripheral helper T cells (TPHs) are likely to originate from synovial tissue, undergo activation and exhaustion, and are subsequently released into the peripheral blood. Notably, among all immune cell types, TPHs were found to have the most intense associations with disease activity. In addition, CD8 effector T cells could be clustered into two groups with different cytokine expressions and play distinct roles in RA development. By integrating single-cell data with bulk sequencing from two large cohorts, we identified interactions among TPHs, CD8 cells, CD16 monocytes, and DCs that strongly contribute to the proinflammatory local environment in RA joints. Of note, the swollen 28-joint counts exhibited a more pronounced association with this immune environment compared to other disease activity indexes. The immune environment alternated significantly from PBMCs to SF, which indicated that a series of immune cells was involved in proinflammatory responses in the local joints of RA patients. By integrating single-cell data with two large cohorts, we have uncovered associations between specific immune cell populations and clinical features. This integration provides a rapid and precise methodology for assessing local immune activation, offering valuable insights into the pathophysiological mechanisms at play in RA.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of binding and authentic virus-neutralizing activities of immune sera induced by various monkeypox virus antigens.","authors":"Shuo Song, Zuning Ren, Jiayin Chen, Mengjun Li, Yushan Jiang, Yingxia Liu, Bao Zhang, Hongzhou Lu, Wei Zhao, Chenguang Shen, Yang Yang","doi":"10.1007/s12026-024-09499-0","DOIUrl":"10.1007/s12026-024-09499-0","url":null,"abstract":"<p><p>Monkeypox cases continue to increase globally, and there is an urgent need to develop a highly effective vaccine against monkeypox. This study investigated the binding and authentic-virus neutralizing activities of sera from mice immunized with EEV (extracellularly enveloped viruses) antigens B6R and A35R, and IMV (intrinsic material viruses) antigens M1R, A29L, E8L, and H3L against monkeypox virus. The results showed that immunizations of A35R and E8L could only induce lower titers of binding antibodies, in contrast, immunization of M1R induced the highest titers of binding antibodies, while immunization of B6R, H3L, and A29L induced moderate titers of binding antibodies. For the live monkeypox virus neutralization assay, the results showed that immunization with two doses of EEV antigen B6R did not effectively induce humoral immune responses to neutralize monkeypox live virus, immunization with EEV-A35R only induced weak monkeypox-neutralizing antibodies. In contrast, the immunization of the four types of monkeypox virus IMV antigens can all induce neutralizing antibodies against authentic monkeypox virus, among them, A29L and H3L induced the highest neutralizing antibody titers. The results of this study provide important references for the selection of antigens in the development of the next generation of monkeypox vaccines.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-141-3p attenuates inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway.","authors":"Guangwen Long, Qian Zhang, Xiulin Yang, Hongpeng Sun, Chunling Ji","doi":"10.1007/s12026-024-09503-7","DOIUrl":"10.1007/s12026-024-09503-7","url":null,"abstract":"<p><p>The present research aimed to investigate the effects and mechanisms of microRNA (miR)-141-3p on pulmonary fibrosis of acute respiratory distress syndrome (ARDS). A rat ARDS model was established by the intratracheal drip of 10 mg/kg lipopolysaccharide (LPS). miR-141-3p and Kelch-like ECH-associated protein 1 (Keap1) expression was detected using RT-qPCR assay. Inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissues were measured with enzyme-linked immunosorbent assay (ELISA). Lung fibrosis was evaluated using Masson's trichrome staining and hydroxyproline assay kits. Tissue oxidative stress marker levels were assessed by a commercial kit. Protein variations in the EMT pathway and Keap1/nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway were investigated by Western blot analysis. Targeting relationship verified by dual-luciferase reporter assay. The expression of miR-141-3p was significantly upregulated in LPS-induced ARDS rats, while Keap1 was downregulated. Overexpression of miR-141-3p decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, superoxide dismutase (SOD), and glutathione (GSH) while elevating malondialdehyde (MDA) expression in LPS-induced ARDS rats. Elevation of miR-141-3p reduced fibrosis scores, enhanced E-cadherin protein expression, and decreased vimentin and α-SMA protein expression in LPS-induced ARDS rats. This elevation of miR-141-3p also upregulated Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxido-reductase-1 (NQO1) proteins levels. Moreover, Keap1 overexpression reversed the inhibitory effects of miR-141-3p on LPS-triggered inflammation, oxidative stress, and fibrosis. miR-141-3p may attenuate inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway. Our study provides new ideas for the treatment of ARDS.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}