BMC Immunology最新文献

{"title":"IWR-1 attenuates the promotional effect of IL-36γ in a mouse model of psoriasis.","authors":"Wen-Ming Wang, Yi-Meng Gao, Xiao-Feng Zheng, Hong-Zhong Jin","doi":"10.1186/s12865-024-00669-1","DOIUrl":"https://doi.org/10.1186/s12865-024-00669-1","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disease. The Wnt/β-catenin signaling pathway is essential for the regulation of adult stem cells, homeostasis, and tissue regeneration; however, the relationship between this pathway and interleukin (IL)-36γ in the pathogenesis of psoriasis remains unclear.</p><p><strong>Methods: </strong>In this study, psoriasiform model mice were established using imiquimod (IMQ) induction. Hematoxylin and eosin (H&E) staining was used to evaluate pathological morphologies, while immunohistochemistry was used to verify the expression patterns of β-catenin and the inflammatory factors IL-6, IL-17 A, and interferon (IFN)-γ.</p><p><strong>Results: </strong>IL-36γ treatment increased psoriasis area and severity index scores, and enhanced proliferation of keratinocytes in IMQ-induced psoriatic mice. The effects of IL-36γ on the severity of psoriasiform lesions and epidermal hyperplasia were partly inhibited by IWR-1, which is an inhibitor of the Wnt/β-catenin signaling pathway. Furthermore, the levels of proinflammatory cytokines and molecules involved in the Wnt/β-catenin signaling pathway in psoriatic mouse skin, including IL-6, IL-17 A, IFN-γ, β-catenin, and Dickkopf-1 (DKK1), were upregulated by treatment with IL-36γ. Consistently, the effects of IL-36γ on the inflammatory response and the Wnt/β-catenin signaling pathway were alleviated by IWR-1.</p><p><strong>Conclusions: </strong>Taken together, our findings suggested that inhibition of the Wnt/β-catenin signaling pathway may be useful in the alleviation of IL-36γ-induced psoriasis-like lesions.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"78"},"PeriodicalIF":2.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692575","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":"Bioinformatics designing of an mRNA vaccine for Mokola virus (MOKV) using immunoinformatics as a secure strategy for successful vaccine development.","authors":"Elijah Kolawole Oladipo, James Akinwumi Ogunniran, Oluwaseyi Samuel Akinpelu, Tosin Omoboyede Omole, Stephen Feranmi Adeyemo, Boluwatife Ayobami Irewolede, Bamidele Abiodun Iwalokun, Olumide Faith Ajani, Helen Onyeaka","doi":"10.1186/s12865-024-00668-2","DOIUrl":"10.1186/s12865-024-00668-2","url":null,"abstract":"<p><p>The Mokola Virus belongs to the family Rhabdoviridae and is genotype 3 of the Lyssavirus genera. A small number of cases of animal and human encephalomyelitis, mainly scattered over sub-Saharan Africa, have been linked to the Mokola Virus (MOKV). Currently there is no vaccine to protect against MOKV infection in people or animals. It has been proven that rabies vaccination does not confer immunity against MOKV infection, even though MOKV and the rabies virus are related. Using immunoinformatics approaches, this study designed an mRNA vaccine that can protect against all the five glycoproteins of the Mokola virus. NCBI was used to obtain the viral sequences, which were then screened for antigenicity, allergenicity, toxicity, B-cell epitopes, CD8 + T lymphocytes (CTL), and CD4 + T lymphocytes (HTL). These epitopes were used in the construction of the vaccine. Some extra co-translational residues were added to the mRNA vaccine construct. Its molecular weight is 129.19083 kDa, and its estimated pI is 8.58. It interacts rather steadily and with limited deformability with TLR 3, among other human innate immune receptors. Overall, the results show that the produced candidate vaccine is non-allergen, non-toxic, and can elicit T-cell and B-cell immune responses. These findings can further be subjected to in-vivo and in-vitro techniques for validation.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"77"},"PeriodicalIF":2.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675146","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":"Comprehensive analysis of the relationship between RNA modification writers and immune microenvironment in head and neck squamous cell carcinoma.","authors":"Wei Li, Ying Chen, Yao Zhang, Wen Wen, Yingying Lu","doi":"10.1186/s12865-024-00667-3","DOIUrl":"10.1186/s12865-024-00667-3","url":null,"abstract":"<p><strong>Objectives: </strong>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Four types of RNA modification writers (m6A, m1A, A-I editing, and APA) are widely involved in tumorigenesis and the TME. We aimed to comprehensively explore the role of the four RNA modification writers in the progression and immune microenvironment of HNSCC.</p><p><strong>Materials and methods: </strong>We first obtained transcription profile data and transcriptional variation of the four types of RNA modification writers from The Cancer Genome Atlas (TCGA) database. HNSCC patients in TCGA dataset were divided into different clusters based on the four types of RNA modification writers. Univariate Cox and Least absolute shrinkage and selection operator (LASSO) analyses were performed to conduct a Writer-score scoring system, which was successfully verified in the GSE65858 dataset and our clinical sample dataset. Finally, we evaluated the relationship between different RNA modification clusters (Writer-score) and immunological characteristics of HNSCC.</p><p><strong>Results: </strong>Two different RNA modification clusters (A and B) were obtained. These RNA modification clusters (Writer-score) were strongly associated with immunological characteristics (immunomodulators, cancer immunity cycles, infiltrating immune cells (TIICs), inhibitory immune checkpoints, and T cell inflamed score (TIS)) of HNSCC.</p><p><strong>Conclusions: </strong>This study identified two different RNA modification clusters and explored the potential relationship between RNA modification clusters (Writer-score) and immunological characteristics, offering a new theoretical basis for precision immunotherapy in patients with HNSCC.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"76"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614292","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":"Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats.","authors":"Hasan Çalışkan, Deniz Önal, Erhan Nalçacı","doi":"10.1186/s12865-024-00665-5","DOIUrl":"10.1186/s12865-024-00665-5","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to investigate the anxiolytic effect of darbepoetin alpha (DEPO), an erythropoietin derivative, in a neuroinflammation model regarding different behaviors and biological pathways.</p><p><strong>Methods: </strong>Forty adult male Wistar albino rats were divided into four groups (control, LPS, DEPO, and DEPO + LPS). The rats were treated with 5 µg /kg DEPO once a week for four weeks, after which neuroinflammation was induced with 2 mg/kg lipopolysaccharide (LPS). The elevated plus maze, open-field, and light‒dark box tests were conducted to assess anxiety levels. Harderian gland secretions were scored via observation. Tumor necrosis factor alpha (TNF-α), Interleukin-1-beta (IL-1β), brain-derived growth factor (BDNF), serotonin, cortisol, total antioxidant/oxidant (TAS/TOS), and total/free thiol levels were measured in the prefrontal cortex, striatum, and serum.</p><p><strong>Results: </strong>DEPO had a potent anxiolytic effect on both DEPO and DEPO + LPS groups. Compared to the control group, DEPO administration caused an increase in serotonin and BDNF levels and decreased basal cortisol and TNF-α levels in naive rats. IL-1β did not alter after DEPO administration in naive rats. Prophylactic DEPO treatment remarkably downregulated cortisol, IL-1β, and TNF-α in the DEPO + LPS group. In addition, prophylactic DEPO administration significantly attenuated the decrease in serotonin and BDNF levels in the DEPO + LPS group. Furthermore, DEPO ameliorated excessive harderian gland secretion in the DEPO + LPS group. Compared with those in the control group, the free thiol content in the serum increased after DEPO administration. No similar effect was seen in the DEPO + LPS group receiving prophylactic DEPO. TAS showed no difference among all experimental groups. DEPO administration increased TOS and OSI in the serum and prefrontal cortex but not in the striatum. This effect was not seen in the DEPO + LPS group.</p><p><strong>Conclusion: </strong>Darbepoetin alpha had an anxiolytic effect on many physiological mechanisms in a neuroinflammation model and naive rats.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"75"},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614299","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":"Transcriptomic evidence for atopic dermatitis as a systemic disease in NC/Nga mice.","authors":"Young-Won Kim, Eun-A Ko, Jehee Jang, Seohyun Jeong, Donghyeon Kim, Jung Soo Suh, Se-Yeon Lee, Inja Lim, Sung-Cherl Jung, Jung-Ha Kim, Tong Zhou, Hyoweon Bang, Jae-Hong Ko","doi":"10.1186/s12865-024-00666-4","DOIUrl":"10.1186/s12865-024-00666-4","url":null,"abstract":"<p><strong>Background: </strong>In the current study, we evaluated whether atopic dermatitis (AD) affects the entire body rather than being limited to skin barrier damage and inflammation. We hypothesized that medium-term exposure of distant organs to systemic inflammatory cytokines in sub-chronic inflammatory skin diseases has detrimental effects on distant tissues.</p><p><strong>Results: </strong>Our findings demonstrated the dysregulation of genes and pathways associated with inflammation and the skin barrier, as well as genes and pathways involved in muscle development that respond to chemicals or stress in muscle tissues, all of which were reversed by hydrocortisone (Hc) administration. The expression of Ces1d showed significant differences during disease onset and after treatment in both skin and skeletal muscle, suggesting that Ces1d is likely responsible for the alleviation of subchronic AD.</p><p><strong>Conclusions: </strong>Using NC/Nga mice with AD-like symptoms, we compared the transcriptomes of the skeletal muscle (a tissue that is relatively distant from the skin) with those of the skin (the lesion induction site) before and after disease induction, after which Hc was administered. Although further study is needed to better understand the effects of Ces1d on AD, skeletal muscle was associated with AD pathogenesis, and AD-like symptoms appeared to affect the body in a systemic manner. Given the importance of evidence-based medicine and the development of precision medicine, our findings provide insights into the mechanisms of AD onset and progression.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"74"},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614304","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":"Warning values of serum total kappa/lambda ratio for M-proteinemia.","authors":"Jie Lu, Ying Zhu, Huifang Huang, Qian Yang, Songnan Qi","doi":"10.1186/s12865-024-00664-6","DOIUrl":"10.1186/s12865-024-00664-6","url":null,"abstract":"<p><strong>Background: </strong>To introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia.</p><p><strong>Methods: </strong>156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency.</p><p><strong>Results: </strong>The optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%.</p><p><strong>Conclusions: </strong>K/L > 2.31 and K/L < 1.43 can be used as warning values for M-proteinemia. In addition, the content of the heavy chain in IgA- or IgM-type M-proteinemia may be considered to improve the detection rate.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"73"},"PeriodicalIF":2.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543541","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":"Chemokine CCL2 and its receptor CCR2 in different age groups of patients with COVID-19.","authors":"Vahid Bagheri, Hossein Khorramdelazad, Mehdi Kafi, Mitra Abbasifard","doi":"10.1186/s12865-024-00662-8","DOIUrl":"10.1186/s12865-024-00662-8","url":null,"abstract":"<p><strong>Background: </strong>Despite the development of various antiviral drugs, most of them are not effective in the treatment of coronavirus disease 2019 (COVID-19) as a hyperinflammatory disorder. Chemokine (C-C motif) ligand 2 (CCL2) is one of the critical CC chemokines involved in the pathogenesis and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This study aimed to investigate the expression of CCL2 and CC chemokine receptor 2 (CCR2) in COVID-19 patients.</p><p><strong>Methods: </strong>Peripheral blood samples were collected from 60 confirmed COVID-19 patients and 60 age-matched healthy subjects. The ages of the subjects were categorized as follows: up to 20 years, 20 to 40 years, 40 to 60 years, and more than 60 years. CCL2 serum levels were measured using the enzyme-linked immunosorbent assay (ELISA). CCR2 gene expression in peripheral blood mononuclear cells (PBMCs) was measured employing real-time polymerase chain reaction (PCR).</p><p><strong>Results: </strong>In all age groups, CCL2 serum levels were significantly elevated in patients compared to healthy controls (P < 0.0001). CCL2 levels were higher in severe patients than in moderate patients. Moreover, CCR2 expression by PBMCs was higher in patients compared to control subjects. However, a significant difference between patients and controls over 60 years of age was identified (P = 0.0353). There was no significant difference in CCR2 expression between moderate and severe COVID-19 patients.</p><p><strong>Conclusions: </strong>Taken together, the findings demonstrate that CCL2 and CCR2 are upregulated in COVID-19 patients at protein and mRNA levels, respectively. Therefore, the CCL2/CCR2 axis may be a potential therapeutic target in order to improve patient outcomes.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"72"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494812","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":"A novel approach to immune thrombocytopenia intervention: modulating intestinal homeostasis.","authors":"Hui Sun, Lixiang Yan, Lijun Fang, Zhexin Shi","doi":"10.1186/s12865-024-00660-w","DOIUrl":"10.1186/s12865-024-00660-w","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is a prevalent hemorrhage condition that causes notable immune-related abnormalities. Recently discovered data has shown that the intestinal flora plays a crucial role in maintaining a balanced immune system. Furthermore, an imbalance in gut flora has the potential to increase the possibility of developing ITP. Moreover, some studies reported a strong link between inflammatory bowel disease (IBD) and ITP. In this review, we described the significance of gut immunity in ITP. In addition, we explored the associations between gut flora and ITP as well as IBD and ITP. Finally, we examined the effectiveness of existing therapies that regulate gut homeostasis and their impact on the prognosis of patients with ITP.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"71"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494811","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":"Retraction Note: Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.","authors":"Hassan A Saad, Azza Baz, Mohamed Riad, Mohamed E Eraky, Ahmed El-Taher, Mohamed I Farid, Khaled Sharaf, Huda E M Said, Lotfy A Ibrahim","doi":"10.1186/s12865-024-00663-7","DOIUrl":"10.1186/s12865-024-00663-7","url":null,"abstract":"","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"70"},"PeriodicalIF":2.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457638","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":"High glucose condition aggravates inflammatory response induced by Porphyromonas gingivalis in THP-1 macrophages via autophagy inhibition.","authors":"Yuri Song, Jin-Ju Kwon, Hee Sam Na, Si Yeong Kim, Sang-Hun Shin, Jin Chung","doi":"10.1186/s12865-024-00655-7","DOIUrl":"https://doi.org/10.1186/s12865-024-00655-7","url":null,"abstract":"<p><strong>Background: </strong>Porphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection.</p><p><strong>Results: </strong>The expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis-induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice.</p><p><strong>Conclusions: </strong>High-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"69"},"PeriodicalIF":2.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457636","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}