Immunogenetics最新文献

{"title":"Decoding the genetic landscape of juvenile dermatomyositis: insights from phosphorylation-associated single nucleotide polymorphisms.","authors":"Huan Zhang, Zhentao Zhang, Kedi Fan, Hongru Chen, Yufan Guo, Xingbo Mo","doi":"10.1007/s00251-024-01350-y","DOIUrl":"10.1007/s00251-024-01350-y","url":null,"abstract":"<p><p>Genome-wide association studies (GWASs) have identified genetic susceptibility loci associated with juvenile dermatomyositis (JDM). Single nucleotide polymorphisms related to phosphorylation (phosSNPs) are critical nonsynonymous mutations exerting substantial influence on gene expression regulation. The aim of this study was to identify JDM susceptibility genes in the GWAS loci by the use of phosSNPs. We explored quantitative trait loci (QTLs) among the phosSNPs associated with JDM using data from eQTL (bulk tissues and single-cell) and pQTL studies. For gene expression and protein levels significantly influenced by JDM-associated phosSNPs, we assessed their associations with JDM through MR analyses. Additionally, we conducted differential expression gene analyses, incorporating single-cell transcriptomic profiling of 6 JDM cases and 11 juvenile controls (99,396 cells). We identified 31 phosSNPs situated in the 6p21 locus that were associated with JDM. Half of these phosSNPs showed effects on gene expression in various cells and circulating protein levels. In MR analyses, we established associations between the expression levels of pivotal JDM-associated genes, including MICB, C4A, HLA-DRB1, HLA-DRB5, and PSMB9, in skin, muscle, or blood cells and circulating levels of C4A, with JDM. Utilizing single-cell eQTL data, we identified a total of 276 association signals across 14 distinct immune cell types for 28 phosSNPs. Further insights were gained through single-cell differential expression analysis, revealing differential expression of PSMB9, HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQA1, HLA-DQB1, and HLA-DRB1 in immune cells. The present study pinpointed phosSNPs within susceptibility genes for JDM and unraveled the intricate relationships among these SNPs, gene expression levels, and JDM.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"291-304"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859597","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":"The effect of circulating cytokines on the risk of systemic lupus erythematosus: Mendelian randomization and observational study.","authors":"Dan Xue, Yu Qian, Xiao Tu, Mu He, Fengling Xing, Yunqing Ren, Chengda Yuan","doi":"10.1007/s00251-024-01351-x","DOIUrl":"10.1007/s00251-024-01351-x","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, the etiology of which involves the alterations in circulating cytokine levels. However, the cause-and-effect relationships and in-depth clinical relevance of them remain to be systematically investigated. We conducted a two-sample Mendelian randomization (MR) study to assess the causality of circulating cytokine levels and SLE and found that genetically determined elevated CTACK and IL-18 were associated with an increased risk of SLE, whereas a higher level of GRO-a was associated with decreased risk. Furthermore, we performed an observational study to further reveal the association between 27 cytokines and the severity measured by SLEDAI score, as well as lupus nephritis (LN), of SLE. We identified six cytokines (MCP1, MIP1β, CTACK, IP10, HGF, IL18, IL13) that were identified as associated with the clinical severity of SLE, and five cytokines, especially IL18, were related with LN and may have good diagnostic value. Moreover, we also predicted four compounds that might have good binding activities with IL18. The evidence supported a potential causal role of circulating cytokines on the risk of SLE. Targeting IL18 might be a meaningful strategy for the prevention or treatment of SLE, especially in LN patients.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"315-322"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOD alleles at Idd1 and Idd2 loci drive exocrine pancreatic inflammation.","authors":"Laurence Caron, Daria Vdovenko, Félix Lombard-Vadnais, Sylvie Lesage","doi":"10.1007/s00251-024-01352-w","DOIUrl":"10.1007/s00251-024-01352-w","url":null,"abstract":"<p><p>Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes and have enabled the identification of several loci associated with diabetes susceptibility, termed insulin-dependent diabetes (Idd). The generation of congenic mice has allowed the characterization of the impact of several loci on disease susceptibility. For instance, NOD.B6-Idd1 and B6.NOD-Idd1 congenic mice were instrumental in demonstrating that susceptibility alleles at the MHC locus (known as Idd1) are necessary but not sufficient for autoimmune diabetes progression. We previously showed that diabetes resistance alleles at the Idd2 locus provide significant protection from autoimmune diabetes onset, second to Idd1. In search of the minimal genetic factors required for T1D onset, we generated B6.Idd1.Idd2 double-congenic mice. Although the combination of Idd1 and Idd2 is not sufficient to induce diabetes onset, we observed immune infiltration in the exocrine pancreas of B6.Idd2 mice, as well as an increase in neutrophils and pancreatic tissue fibrosis. In addition, we observed phenotypic differences in T-cell subsets from B6.Idd1.Idd2 mice relative to single-congenic mice, suggesting epistatic interaction between Idd1 and Idd2 in modulating T-cell function. Altogether, these data show that Idd1 and Idd2 susceptibility alleles are not sufficient for autoimmune diabetes but contribute to inflammation and immune infiltration in the pancreas.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"323-333"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107020","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":"Bioinformatic analysis predicts the regulatory function of noncoding SNPs associated with Long COVID-19 syndrome.","authors":"Amit K Maiti","doi":"10.1007/s00251-024-01348-6","DOIUrl":"10.1007/s00251-024-01348-6","url":null,"abstract":"<p><p>Long or Post COVID-19 is a condition of collected symptoms persisted after recovery from COVID-19. Host genetic factors play a crucial role in developing Long COVID-19, and GWAS studies identified several SNPs/genes in various ethnic populations. In African-American population two SNPS, rs10999901 (C>T, p = 3.6E-08, OR = 1.39, MAF-0,27, GRCH38, chr10:71584799 bp) and rs1868001 (G>A, p = 6.7E-09, OR = 1.40, MAF-0.46, GRCH38, chr10:71587815 bp) and in Hispanic population, rs3759084 (A>C, p = 9.7E-09, OR = 1.56, MAF-0.17, chr12: 81,110,156 bp) are strongly associated with Long COVID-19. All these three SNPs reside in noncoding regions implying their regulatory function in the genome. In silico dissection suggests that rs10999901 and rs1868001 physically interact with the CDH23 and C10orf105 genes. Both SNPs act as distant enhancers and bind with several transcription factors (TFs). Further, rs10999901 SNP is a CpG that is methylated in CD4++ T cells and monocytes and loses its methylation due to transition from C>T. rs3759084 is located in the promoter (- 687 bp) of MYF5, acts as a distant enhancer, and physically interacts with PTPRQ. These results offer plausible explanations for their association and provide the basis for experiments to dissect the development of symptoms of Long COVID-19.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"279-290"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748113","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":"Using bioinformatics to investigate functional diversity: a case study of MHC diversity in koalas.","authors":"Luke W Silver, Elspeth A McLennan, Julian Beaman, Karen Burke da Silva, Peter Timms, Carolyn J Hogg, Katherine Belov","doi":"10.1007/s00251-024-01356-6","DOIUrl":"10.1007/s00251-024-01356-6","url":null,"abstract":"<p><p>Conservation genomics can greatly improve conservation outcomes of threatened populations, including those impacted by disease. Understanding diversity within immune gene families, including the major histocompatibility complex (MHC) and toll-like receptors (TLR), is important due to the role they play in disease resilience and susceptibility. With recent advancements in sequencing technologies and bioinformatic tools, the cost of generating high-quality sequence data has significantly decreased and made it possible to investigate diversity across entire gene families in large numbers of individuals compared to investigating only a few genes or a few populations previously. Here, we use the koala as a case study for investigating functional diversity across populations. We utilised previous target enrichment data and 438 whole genomes to firstly, determine the level of sequencing depth required to investigate MHC diversity and, secondly, determine the current level of diversity in MHC genes in koala populations. We determined for low complexity, conserved genes such as TLR genes 10 × sequencing depth is sufficient to reliably genotype more than 90% of variants, whereas for complex genes such as the MHC greater than 20 × and preferably 30 × sequencing depth is required. We used whole genome data to identify 270 biallelic SNPs across 24 MHC genes as well as copy number variation (CNV) within class I and class II genes and conduct supertype analysis. Overall, we have provided a bioinformatic workflow for investigating variation in a complex immune gene family from whole genome sequencing data and determined current levels of diversity within koala MHC genes.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"381-395"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The characteristic of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1 alleles in Zhejiang Han population.","authors":"Sudan Tao, Xuan You, Nanying Chen, Lina Dong, Shuoxian Zhao, Yizhen He, Wei Zhang, Faming Zhu","doi":"10.1007/s00251-024-01349-5","DOIUrl":"10.1007/s00251-024-01349-5","url":null,"abstract":"<p><p>The Zhejiang Han population, a subgroup of the Southern Han ethnic group, resides in Zhejiang Province, situated on the southeast coast of China. In this study, we conducted HLA genotyping for 813 voluntary umbilical cord blood donors from the Zhejiang Han population, targeting 11 HLA loci, namely HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, using the next-generation sequencing method. Our analysis of the alleles and haplotypes revealed a high degree of polymorphism within these loci. A total of 289 unique HLA alleles were identified, with the HLA-B locus exhibiting the most significant diversity, while HLA-DRB4 displayed the lowest variation. Due to the inherent limitations of the sequencing method, some unresolvable alleles in the specific loci, such as HLA-DRB1, HLA-DPA1, and HLA-DPB1, were assigned as G group designation. In our comprehensive analysis across all 11 HLA loci, a total of 1204 haplotypes were estimated. The distribution of these alleles was similar to those of the Chinese Southern Han population while highly different from the Caucasian population. These findings contribute to a deeper understanding of the genetic characteristics of HLA loci within the Chinese Southern Han population.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"305-314"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897349","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":"Spatial variation in toll-like receptor diversity in koala populations across their geographic distribution.","authors":"Jian Cui, Kimberley C Batley, Luke W Silver, Elspeth A McLennan, Carolyn J Hogg, Katherine Belov","doi":"10.1007/s00251-024-01365-5","DOIUrl":"10.1007/s00251-024-01365-5","url":null,"abstract":"<p><p>The koala (Phascolarctos cinereus) is an iconic Australian species that is listed as endangered in the northern parts of its range due to loss of habitat, disease, and road deaths. Diseases contribute significantly to the decline of koala populations, primarily Chlamydia and koala retrovirus. The distribution of these diseases across the species' range, however, is not even. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognising and responding to various pathogens. Variations in TLR genes can influence an individual's susceptibility or resistance to infectious diseases. The aim of this study was to identify koala TLR diversity across the east coast of Australia using 413 re-sequenced genomes at 30 × coverage. We identified 45 single-nucleotide polymorphisms (SNP) leading to 51 alleles within ten TLR genes. Our results show that the diversity of TLR genes in the koala forms four distinct genetic groups, which are consistent with the diversity of the koala major histocompatibility complex (MHC), another key immune gene family. The bioinformatics approach presented here has broad applicability to other threatened species with existing genomic resources.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"5"},"PeriodicalIF":2.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Complement Factor H gene polymorphisms and their association with clinical manifestations ofleptospirosis.","authors":"Lazara Elena Santiesteban-Lores, Leonardo Moura Midon, ThirsaAlvares Franco, Luciano Marcondes de Oliveira, Sumire Hibi, Yosena Chiani, GdayllonCavalcante Meneses, Elizabeth De Francesco Daher, Denise Moraes Fonseca, Alessandra Pontillo, Lourdes Isaac","doi":"10.1007/s00251-024-01362-8","DOIUrl":"10.1007/s00251-024-01362-8","url":null,"abstract":"<p><p>Leptospirosis is caused by pathogenic leptospires, posing a significant public health problem. Host susceptibility to Leptospira infection is a multifactorial trait, and the host's genetic background can influence both the establishment of infection and the severity of the disease. Complement Factor H (FH) plays a crucial role in the interaction between pathogenic bacteria and the host. Genetic variants in the FH gene CFH have previously been associated with non-infectious diseases. Here, we aimed to analyze the effect of CFH variants on individual susceptibility to leptospirosis and disease severity. To accomplish this, we sequenced CFH exons 7, 9, 21, 22, and 23 in a case/control cohort (184/162) from two endemic leptospirosis areas in Brazil and Argentina. We identified twenty-one single nucleotide variants (SNVs). In the Brazilian cohort, the intronic variant rs34815383 exhibited a higher frequency in patients than in controls, resulting in a significant association with leptospirosis (p = 0.032; OR: 0.32; 95% CI 0.1-1) and also renal disorder (p = 0.001; OR: 5.3; 95%CI 1.8-15.57). This SNV is reported to be a splicing variant, negatively impacting CFH expression, and has previously been associated with Complement-driven renal disease. A second synonymous variant, rs61822181, was significantly less frequent in patients than in controls (p = 0.002; OR: 7.33; 95% CI 1.59-33.7), representing a protective factor against the development of leptospirosis. Our study represents the first documentation of the frequency of CFH SNVs in South America and identifies the variant rs34815383 T > C as a risk factor for leptospirosis and leptospirosis-related renal complications.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"4"},"PeriodicalIF":2.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768594","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":"Exploring the therapeutic potential of interleukin-6 receptor blockade in autoimmune diseases using drug target mendelian randomization.","authors":"Jiaxin Li, Yalin Liu, Zheng Xiao, Chenyang Zang, Peihong Li, Bo Xiao, Luo Zhou","doi":"10.1007/s00251-024-01360-w","DOIUrl":"10.1007/s00251-024-01360-w","url":null,"abstract":"<p><p>The blockade of the interleukin 6 receptor (IL-6R) demonstrates significant potential in various autoimmune diseases (ADs); however, the underlying therapeutic efficacy associated with this approach remains elusive. We conducted a comprehensive Mendelian randomization (MR) analysis based on large-scale genome-wide association studies to investigate the causal relationships between genetically proxied IL-6R blockade weighted by serum C-reactive protein levels and eighteen common ADs. Rheumatoid arthritis, COVID-19 infection, and COVID-19 critical illness were utilized as positive controls. The inverse-variance weighted (IVW) method was utilized as the primary analytical tool, while genetic colocalization analysis was conducted to further substantiate the causalities. Genetically proxied IL-6R blockade exhibited causally protective effects on all positive control diseases. After Bonferroni correction to IVW estimates, genetically proxied IL-6R blockade may significantly increase the risk of asthma (OR=1.031, P=2.15×10^-12) and eczema (OR=1.066, P=5.92×10^-22), while reducing the risk of ankylosing spondylitis (OR=0.341, P=1.39×10^-5), Crohn's disease (OR=0.556, P=2.21×10^-3), and type 1 diabetes (OR=0.410, P=1.78×10^-7). Additionally, genetically proxied IL-6R blockade would suggestively reduce the risk of multiple sclerosis (OR=0.713, P=1.13×10^-2). The results were robust under sensitivity analysis. For genetic colocalization analysis, we identified a shared causal variant rs531479718 linking serum C-reactive protein levels and asthma (posterior probability H4=0.998). Overall, our MR study demonstrated that genetically proxied IL-6R blockade may be causally associated with an increased risk of asthma and eczema, while concurrently diminishing the risk of ankylosing spondylitis, Crohn's disease, type 1 diabetes, and multiple sclerosis. These findings carry substantial implications for informing the therapeutic utilization of IL-6R blockade in the management of ADs.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"3"},"PeriodicalIF":2.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716283","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":"A novel mutation in FNIP1 associated with a syndromic immunodeficiency and cardiomyopathy.","authors":"Ilia Spivak, Atar Lev, Amos J Simon, Ortal Barel, Ido Somekh, Raz Somech","doi":"10.1007/s00251-024-01359-3","DOIUrl":"10.1007/s00251-024-01359-3","url":null,"abstract":"<p><p>Genetic variants in Folliculin interacting protein 1 (FNIP1) were recently discovered as monogenic causes for immunodeficiency and cardiomyopathy, with only a few patients diagnosed thus far. In this study, we describe a patient harboring a novel genetic variant in FNIP1 causing immunodeficiency with cardiac involvement. Clinical and immunological workups were performed. Genetic evaluation utilizing whole-exome sequencing (WES) and Sanger sequencing was conducted. The index patient (subject II-4) presented with hypertrophic cardiomyopathy, recurrent infections, and chronic diarrhea during infancy. Immune workup revealed agammaglobulinemia and a lack of B lymphocytes. Genetic evaluation identified a homozygous 13-bp duplication variant in FNIP1 (c.52_64dupGCGCCCGGCCGCG, p. Asp22GlyfsTer21) resulting in a frameshift in exon 1/18. She was treated with supplemental intravenous immunoglobulins (IVIg) with good control of sinopulmonary and gastrointestinal manifestations. Her sibling (subject II-1) had similar clinical features, along with dysmorphic facial features and hypotony, and succumbed to cardiogenic shock at the age of 2 months, prior to genetic evaluation. Diagnosis of novel immunodeficiencies promotes our understanding of the immune system, enabling genetic counseling as herein, and may assist in the development of novel medical therapies in the future. FNIP1 loss-of-function should be considered in patients presenting in infancy with cardiac manifestations along with agammaglobulinemia (and B-cell lymphopenia).</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"2"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}