Bibliometric analysis of childhood-onset systemic lupus erythematosus from 2000 to 2022.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disorder. When SLE occurs in individuals under the age of 18, it is referred to as childhood-onset SLE (cSLE). Currently, there is a dearth of bibliometric research pertaining to cSLE. METHOD: Relevant studies in the field of cSLE from 2000 to 2022 were screened from the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer software were used to visualize the annual publications, countries, institutions, authors, journals, keywords, and references, after which the authors conducted the scientific analysis. RESULTS: A total of 2857 articles were included in this study, and the number of articles published in the past 20 years showed an overall upwards trend. The most prolific countries are the United States, China, and Brazil; however, the United States, Canada, and the United Kingdom are clearly superior in terms of literary influence, and there is more cooperation between them and their institutions. LUPUS (n = 389) contributed the most to the variance. Brunner, HI's contribution in the field of cSLE is outstanding. The words related to 'lupus nephritis' and 'antibodies' are important words reflected in the keyword network diagram. The keywords included 'evidence-based recommendation', 'validation', 'diagnosis' and 'adult' from 2019, and 'continuous bursts' to the present. CONCLUSION: This study examined the research status of cSLE patients, discussed and analysed the research hotspots and trends in this field, and provided a reference for further research in this field to promote the development of cSLE research.

Bibliometric analysis of global literature productivity in systemic lupus erythematosus from 2013 to 2022.

BACKGROUND: Bibliometric analysis is a mature method for quantitative evaluation of academic productivity. In view of the rapid development of research in the field of systemic lupus erythematosus (SLE) in the past decade, we used bibliometric methods to comprehensively analyze the literature in the field of SLE from 2013 to 2022. METHODS: The relevant literature in the field of SLE from 2013 to 2022 was screened in the Web of Science Core Collection database. After obtaining and sorting out the data, CiteSpace and VOSviewer software were used to visualize the relevant data, and SPSS software was used for scientific statistics. RESULTS: A total of 18,450 publications were included in this study. The number of articles published over the past 10 years has generally shown an upward trend, while Altmetric attention scores have also shown a clear upward trend in general and in most countries. Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers. The USA, China, Japan, Italy, and the UK are the most productive countries, but China and Japan are significantly inferior to other countries in terms of research influence. Four of the top ten authors are at the center of the collaboration network. LUPUS is the most contributing journal. The theme of systemic lupus erythematosus research mainly focuses on the pathogenesis, treatment, and management of SLE, and the emerging trend is related research on machine learning and immune cells. CONCLUSION: This study shows the research status of SLE, clarifies the main contributors in this field, discusses and analyzes the research hotspots and trends in this field, and provides reference for further research in this field to promote the development of SLE research. Key Points • Through bibliometric analysis, Altmetric analysis, and visual analysis, we reveal the global productivity characteristics of SLE-related papers in the past 10 years. • The number of global SLE-related studies has shown a significant increase, indicating that SLE is still a hot topic and deserves further study. • Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers, and the attention of related literature among non-professional researchers is increasing. • The theme of SLE research mainly focuses on the pathogenesis, treatment, and management of SLE. The emerging trend is machine learning and immune cells, which may provide new strategies for the diagnosis and treatment of SLE in the future.

Exploring machine learning methods for predicting systemic lupus erythematosus with herpes.

OBJECTIVES: To investigate whether machine learning, which is widely used in disease prediction and diagnosis based on demographic data and serological markers, can predict herpes occurrence in patients with systemic lupus erythematosus (SLE). METHODS: A total of 286 SLE patients were included in this study, including 200 SLE patients without herpes and 86 SLE patients with herpes. SLE patients were randomly divided into a training group and a test group, and 18 demographic characteristics and serological indicators were compared between the two groups. RESULTS: We selected basophil, monocyte, white blood cell, age, immunoglobulin E, SLE Disease Activity Index, complement 4, neutrophil, and immunoglobulin G as the basic features of modeling. A random forest model had the best performance, but logistic and decision tree analyses had better clinical decision-making benefits. Random forest had a good consistency between feature importance judgment and feature selection. The 10-fold cross-validation showed the optimization of five model parameters. CONCLUSION: The random forest model may be an excellently performing model, which may help clinicians to identify SLE patients whose disease is complicated by herpes early.

Bibliometric and altmetric analysis of research relating to antiphospholipid syndrome based on VOS viewer (2011-2021).

BACKGROUND: Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses in the presence of persistently positive antiphospholipid antibodies. Bibliometric analysis and altmetric analysis are methods of analyzing academic productivity and influence. Currently, the assessment of antiphospholipid syndrome through the above analyses is lacking. This study investigated the quantity and quality of studies in the field of antiphospholipid syndrome and revealed the characteristics of worldwide productivity on this disease by the bibliometric analysis and altmetric analysis. METHODS: The terms "APS," "antiphospholipid syndrome," "antiphospholipid-antibody syndrome," and "Hughes syndrome" were searched on the Web of Science Core Collection from January 1, 2011, to December 31, 2021. Original articles and reviews were selected. We set the filters as "English." RESULTS AND CONCLUSION: A total of 1818 articles were retrieved from 68 countries, of which 20 met the criteria of major active countries. High-income countries contributed 1341 articles (73.48%). The number of articles annually increased significantly in the 10-year period (P < 0.001). The USA (253, 13.91%) was the most productive country. Adjusted by population, Serbia was top of the list. According to the gross domestic product analysis, Serbia ranked first. The most used keywords such as thrombosis and antiphospholipid antibodies were presented by keywords analyses. A content analysis found antithrombotic and anticoagulant therapy as research hotspots. A significant correlation was detected between average citations and altmetric attention scores (P = 0.002) and Mendeley readers count (P < 0.001). From 2011 to 2021, the number of global articles increased rapidly. Most papers came from high-income countries. The relationship between the bibliometric and altmetric analyses were basically consistent; therefore the two can prove/complement each other. Key points • We revealed the global productivity characteristics of the papers related to antiphospholipid syndrome by using the methods of bibliometric analysis and altmetric analysis. • We found the most selected articles that describe the treatment of antiphospholipid syndrome, especially antithrombotic and anticoagulant treatments, which may be the current research hotspot.

Bibliometric and altmetric analyses of publication activity in the field of idiopathic inflammatory myopathy in 2011-2021 based on web of science core collection databases.

Idiopathic inflammatory myopathy is a multisystem autoimmune condition characterized by muscle inflammation (myositis) and interstitial lung disease (ILD). Bibliometric analysis and altmetric analysis are effective methods of evaluating academic productivity and measuring the influence of publications. The purpose of this study is to analyze the research productivity and influence of idiopathic inflammatory myopathy articles using bibliometric analysis and altmetric analysis. Data from articles published between 2011 and 2021 were obtained from the Web of Science. Altmetric attention scores and Mendeley reader counts of the articles were obtained from altmetric evaluations. In the study, 2060 articles related to idiopathic inflammatory myopathy were screened out showing an increasing trend in general. In terms of the origin countries of articles, the United States (n = 467, 22.67%) ranked first. Johns Hopkins University has the largest number of institutions (n = 113). The journals regarding idiopathic inflammatory myopathy and Rheumatology (n = 87) published the most articles. The most cited article was published by Mammen et al. and was related to autoantibodies. Dermatomyositis, polymyositis and other research hotspots were represented by keywords. The results of the altmetric analysis showed that citations, impact factors and h-index were significantly correlated with Altmetric Attention Scores and Mendeley Readers Count (P < 0.05). In summary, bibliometric analysis summarizes the current status of idiopathic inflammatory myopathy research and helps to understand the development of idiopathic inflammatory myopathy in the field between 2011 and 2021. Altmetric analysis was used to evaluate the academic and social influence of articles from the novel perspective of internet attention.

Clinical efficacy and safety of surgery combined with 3D printing for tibial plateau fractures: systematic review and meta-analysis.

Background: The aim of the present study was to systematically evaluate the application value and complications of 3D printing technology on Schatzker tibial platform fracture surgery. Methods: By searching the Cochrane Library, PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM), screening randomized controlled trials (RCTs), and two researchers included the study according to PICOS criteria and performed bias risk assessments. Quality evaluation and data extraction were performed for the included literatures, and meta-analysis was performed for RCTs included at using Review Manager 5.2 software. Results: A total of 15 articles were included in the present study, which included a total of 758 patients, 342 3D printing techniques, 416 conventional surgical procedures. Meta-analysis showed 3D printing operation time [risk difference (RD) =-0.12, 95% CI: -0.16, -0.08, I2=46%, P<0.00001], surgical bleeding [odds ratio (OR) =0.59, 95% CI: 0.45-0.77, I2=0%, P<0.001), intraoperative fluoroscopy (OR =0.59, 95% CI: 0.41-0.85, I2=0%, P=0.004), fracture healing time (OR =0.46, 95% CI: 0.33-0.63, I2=0%, P<0.00001), and complication morbidity (OR =0.60, 95% CI: 0.45-0.81, I2=0%, P=0.001) were significantly lower than in the traditional group. Discussion: 3D printing technology for tibia platform fracture surgery has advantages of reduced operation time, less surgical bleeding, less complications, less intraoperative perspective, fast fracture healing, and can improve the accuracy of tibial platform fracture reduction and postoperative knee function recovery.

Identification of Diagnostic Gene Markers and Immune Infiltration in Systemic Lupus.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, with atypical clinical manifestations and indefinite diagnosis and treatment. So far, the etiology of the disease is not completely clear. Current studies have known the interaction of genetic system, endocrine system, infection, environment, and other factors. Due to abnormal immune function, the human body, with the participation of various immune cells such as T cells and B cells, abnormally recognizes autoantigens, so as to produce a variety of autoantibodies and combine them to form immune complexes. These complexes will stay in the skin, kidney, serosa cavity, large joints, and even the central nervous system, resulting in multisystem damage of the body. The disease is heterogeneous, and it can show different symptoms in different populations and different disease stages; patients with systemic lupus erythematosus need individualized diagnosis and treatment. Therefore, we aimed to search for SLE immune-related hub genes and determine appropriate diagnostic genes to provide help for the detection and treatment of the disease. Methods: Gene expression data of whole blood samples of SLE patients and healthy controls were downloaded from the GEO database. Firstly, we analyzed and identified the differentially expressed genes between SLE and the normal population. Meanwhile, the single-sample gene set enrichment analysis (ssGSEA) was used to identify the activation degree of immune-related pathways based on gene expression profile of different patients, and weighted gene coexpression network analysis (WGCNA) was used to search for coexpressed gene modules associated with immune cells. Then, key networks and corresponding genes were found in the protein-protein interaction (PPI) network. The above corresponding genes were hub genes. After that, this study used receiver operating characteristic (ROC) curve to evaluate hub gene in order to verify its ability to distinguish SLE from the healthy control group, and miRNA and transcription factor regulatory network analyses were performed for hub genes. Results: Through bioinformatics technology, compared with the healthy control group, 2996 common differentially expressed genes (DEGs) were found in SLE patients, of which 1639 genes were upregulated and 1357 genes were downregulated. These differential genes were analyzed by ssGSEA to obtain the enrichment fraction of immune-related pathways. Next, the samples were selected by WGCNA analysis, and a total of 18 functional modules closely related to the pathogenesis of SLE were obtained. Thirdly, the correlation between the above modules and the enrichment fraction of immune-related pathways was analyzed, and the turquoise module with the highest correlation was selected. The 290 differential genes of this module were analyzed by GO and KEGG. The results showed that these genes were mainly enriched in coronavirus disease (COVID-19), ribosome, and human T cell leukemia virus 1 infection pathway. The 290 DEGs with PPI network and 28 genes of key networks were selected. ROC curve showed that 28 hub genes are potential biomarkers of SLE. Conclusion: The 28 hub genes such as RPS7, RPL19, RPS17, and RPS19 may play key roles in the advancement of SLE. The results obtained in this study can provide a reference in a certain direction for the diagnosis and treatment of SLE in the future and can also be used as a new biomarker in clinical practice or drug research.

Exploration of the pathogenesis of Sjögren's syndrome via DNA methylation and transcriptome analyses.

OBJECTIVES: Sjögren's syndrome (SS), a systemic autoimmune disorder, is characterized by dry mouth and eyes. However, SS pathogenesis is poorly understood. We performed bioinformatics analysis to investigate the potential targets and molecular pathogenesis of SS. METHODS: Gene expression profiles (GSE157159) and methylation data (GSE110007) associated with SS patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially methylated positions (DMPs) and differentially expressed genes (DEGs) were identified by the R package limma. The potential biological functions of DEGs were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Key DMPs were selected by overlap and the shrunken centroid algorithm, and corresponding genes were identified as hub genes, with their diagnostic value assessed by receiver operating characteristic (ROC) curves. The potential molecular mechanisms of hub genes were analyzed by protein-protein interaction (PPI) networks and single-gene gene set enrichment analysis (GSEA). Peripheral blood mononuclear cells (PBMCs) were collected from control and SS patients at The Affiliated Hospital of Southwest Medical University and Dazhou Central Hospital. The mRNA levels of hub genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: We identified 788 DMPs and 2457 DEGs between the two groups. Functional enrichment analysis suggested that the DEGs were significantly enriched in T cell activation, leukocyte cell-cell adhesion, and cytokine-cytokine receptor interaction. TSS200, TSS1500, and 1stExon were identified as highly enriched areas of differentially methylated promoter CpG islands (DMCIs). In total, 61 differentially methylated genes (DMGs) were identified by the overlap of 2457 DEGs and 507 genes related to DMPs (DMPGs), of which 21 genes located near TSS200, TSS1500, and 1stExon were selected. Then, three key DMPs and the corresponding hub genes (RUNX3, HLA-DPA1, and CD6) were screened by the shrunken centroid algorithm and calculated to have areas under the ROC curve of 1.000, 0.931, and 0.986, respectively, indicating good diagnostic value. The GSEA results suggested that all three hub genes were highly associated with the immune response. Finally, positive mRNA expression of the three hub genes in clinical SS samples was verified by qRT-PCR, consistent with the GSE157159 data. CONCLUSIONS: The identification of three hub genes provides novel insight into molecular mechanisms and therapeutic targets for SS. Key Points • Hub genes were screened by DNA methylation and transcriptome analyses. • The relative expression of hub genes in peripheral blood samples was verified by qRT-PCR. • HLA-DPA1 was correlated with the pathogenic mechanism of SS.

Association of Growth and Differentiation Factor 15 in Rheumatoid Arthritis.

PURPOSE: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease, which has been demonstrated to correlate with mutated genetics. Growth and differentiation factor 15 (GDF-15) is a member of the transforming growth factor-ß superfamily and is expressed in different organs, tissues and immune cells. To date, limited studies have evaluated plasma levels of GDF-15 in RA patients, and whether GDF-15 gene polymorphisms correlate with RA risk in the Chinese Han population has not been clarified. PATIENTS AND METHODS: This case-control study recruited 910 age- and sex-matched RA patients and healthy controls. Plasma levels of GDF-15 were examined by enzyme linked immunosorbent assay, and polymorphisms (rs1055150, rs1058587, rs3787023, and rs4808793) were genotyped by KASP method. RESULTS: RA patients had higher levels of GDF-15 as compared to that in healthy controls. Patients with positive CRP also showed higher levels of GDF-15 when compared to that in patients with negative CRP. Levels of GDF-15 correlated with disease activity score. Frequencies of GG, GC, GG+GC genotypes and G allele in GDF-15 gene rs1058587 were significantly elevated in RA patients compared to controls. Frequencies of CC genotype and C allele in GDF-15 gene rs3787023 were higher in RA patients compared to controls. Other polymorphisms did not correlate with RA susceptibility. Moreover, the four polymorphisms were not correlated with levels of GDF-15. CONCLUSION: Plasma levels of GDF-15 were elevated in RA patients and GDF-15 gene polymorphisms were related to RA risk in the Chinese Han population.

Bibliometric analysis of the global literature productivity of adult-onset Still's disease (2011-2020).

Adult-onset Still's disease is a nonfamilial, or sporadic, systemic autoinflammatory disorder accompanied by peak fever ≥ 39 °C, arthralgia or arthritis, skin rashes, leukocytosis (≥ 10,000 cells/mm3) with neutrophils ≥ 80%, and other clinical symptoms. This study aimed to analyze the quantity and quality of publications, and to exhibit the current global status and trend of adult-onset Still's disease research. Searched with the search term 'Adult onset Still disease' on the Web of Science for time limited to 2011-2020. Original articles and reviews were selected. A total of 537 articles were retrieved from 44 countries, of which 13 met the criteria of major active countries. High-income countries contributed 378 articles (70.39%). The number of articles annually increased significantly in the 10-year period (P < 0.001). China (n = 90, 16.76%), Japan (n = 79, 14.71%), Italy (n = 59, 10.99%), the United States (n = 52, 9.68%) and South Korea (n = 45, 8.38%) are the five most productive countries. Adjusted by population, Italy led the top list, followed by South Korea and Israel. According to gross domestic product analysis, Italy ranked first, followed by Portugal and Turkey. A significant correlation was detected between average citations and AAS (P = 0.002), MRC (P < 0.001). From 2011 to 2020, the number of global articles was increasing rapidly. Most papers came from high-income countries. The relationship between the bibliometric and altmetric analyses are basically consistent, therefore the two can prove/complement each other.

Association of TNFSF4 Gene Polymorphisms and Plasma TNFSF4 Level with Risk of Systemic Lupus Erythematosus in a Chinese Population.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease. Tumor necrosis factor ligand superfamily member 4 (TNFSF4) is an inflammatory factor that has been discussed in different inflammatory diseases and cancers. However, relationship between TNFSF4 and SLE is limited. MATERIAL AND METHODS: The present case-control study recruited 400 SLE patients and 600 healthy controls from Southern Chinese Han origin. Plasma levels of TNFSF4 were tested by enzyme linked-immunosorbent assay, and association of rs2205960, rs704840, rs844648, rs3850641 and rs17568 polymorphisms in TNFSF4 gene with SLE risk was evaluated by TaqMan assay according to genotyping. RESULTS: Plasma levels of TNFSF4 were significantly higher in SLE patients than that in healthy controls (390.87 (189.10-906.01) versus 132. 70 (81.27-195.58) pg/ml, P < 0.001). Increased levels of TNFSF4 were positively related to SLE disease activity score, optic nerve injury, leukopenia, and hypocompleminemia. Genotype TT+TG, allele T of rs2205960, genotype GG+GT of rs704840, genotype AA of rs844648 and rs17568 were significantly related to SLE risk (all P < 0.05). Moreover, polymorphism rs844648 was related to SLE patients with clinical feature rash either for genotype AA or allele A. CONCLUSION: TNFSF4 was elevated in SLE patients and may associate with SLE susceptibility in Southern Chinese Han population.

Carotid intima-media thickness in patients with hyperuricemia: a systematic review and meta-analysis.

OBJECTIVE: Despite the high incidence and mortality of cardiovascular events in hyperuricemia patients, the role of serum uric acid in cardiovascular diseases is still controversial. The aim of this meta-analysis was to explore the difference of carotid intima-media thickness in hyperuricemia and control groups. METHODS: We performed this meta-analysis by searching the PubMed, Cochrane Library, Embase and Web of Science databases up to July 2020. The 95% confidence intervals and standard mean differences were calculated to analyze the differences in carotid intima-media thickness in hyperuricemia groups and control groups. Sensitivity analysis, subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Publication bias was evaluated by funnel plot and Begg's regression test. We used Stata 14.0 software to complete our analyses. RESULTS: A total of 8 articles were included. The results showed that there was a significant increase in carotid intima-media thickness in the hyperuricemia groups compared with the control groups [SMD = 0.264, 95% CI (0.161-0.366), P < 0.001]. Subgroup analyses showed that age, sample size, blood pressure and body mass index were not the source of heterogeneity. Meta-regression enrolled the method of CIMT measurement, location, age, smoking and diabetes mellitus as categorical variables, but none of these factors was found to be significant in the model. The Begg's test value (P = 0.174) was greater than 0.05, indicating there was no publication bias. CONCLUSION: The results showed that carotid intima-media thickness was increased in hyperuricemia patients compared with controls, which indicated that hyperuricemia patients may have a higher risk of cardiovascular diseases.

Does vitamin D improve symptomatic and structural outcomes in knee osteoarthritis? A systematic review and meta-analysis.

OBJECTIVE: To provide evidence on the effects of vitamin D supplementation on knee osteoarthritis (KOA) and new targets for clinical prevention and treatment of KOA. METHOD: The PubMed, Embase, Web of science, Wanfang, CNKI and SinoMed databases were retrieved to investigate the effects of vitamin D supplementation on patients with KOA. The search time was from databases establishment to 15 November 2020. RevMan5.3 software was used for meta-analysis. The results were expressed as standardized mean difference (SMD) with 95% confidence interval (CI) or weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: A total of 1599 patients with osteoarthritis of the knee were included in the study, which involved six articles. The results of the meta-analysis showed that vitamin D supplementation is statistically significant for WOMAC score (SMD = - 0.67, 95% CI - 1.23 to - 0.12) in patients with KOA, including WOMAC pain score (SMD = - 0.32, 95% CI - 0.63 to - 0.02), function score (SMD = - 0.34, 95% CI - 0.60 to - 0.08) and stiffness score (SMD = - 0.13, 95% CI - 0.26 to - 0.01). In subgroup analysis, vitamin D supplementation less than 2000 IU was statistically significant for the reduction of stiffness score (SMD = - 0.22, 95% CI - 0.40 to - 0.04). Vitamin D supplements can reduce synovial fluid volume progression in patients with KOA (SMD = - 0.20, 95% CI - 0.39 to - 0.02). There was no statistical significance in improving tibia cartilage volume (SMD = 0.12, 95% CI - 0.05 to 0.29), joint space width (SMD = - 0.10, 95% CI - 0.26 to 0.05) and bone marrow lesions (SMD = 0.03, 95% CI - 0.26 to 0.31). CONCLUSION: Vitamin D supplements can improve WOMAC pain and function in patients with KOA. But there is a lack of strong evidence that vitamin D supplementation can prevent structural progression in patients with KOA.

MicroRNA-23a-5p regulates cell proliferation, migration and inflammation of TNF-α-stimulated human fibroblast-like MH7A synoviocytes by targeting TLR4 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint inflammation. RA synovial fibroblasts (RASFs) constitute a major cell subset of the RA synovia. MicroRNAs (miRNAs/miRs) have been reported to serve a role in the activation and proliferation of RASFs. The present study aimed to investigate the effects and underlying mechanisms of miR-23a-5p on RA progression. Peripheral blood was collected from patients with RA (n=20) to analyze the expression levels of miR-23a-5p. The effects of miR-23a-5p on cell apoptosis, proliferation and migration in MH7A cells were determined in TNF-α-treated human fibroblast-like synoviocytes (MH7A cells) by flow cytometry, colony formation assay and Transwell assay, respectively. The cell cycle distribution was evaluated using flow cytometry. The binding relationship between miR-23a-5p and toll-like receptor (TLR) 4 was analyzed using a dual luciferase reporter gene assay. ELISA and reverse transcription-quantitative PCR assays were used to detect the levels of the inflammatory factors IL-6, IL-1ß and IL-10. The expression levels of apoptosis- and migration-related proteins were analyzed using western blotting. The results of the present study revealed that the expression levels of miR-23a-5p were significantly downregulated in the plasma of patients with RA and in MH7A cells. In addition, the TNF-α-induced increase in the cell proliferative and migratory rates and the production of IL-6 and IL-1ß were markedly inhibited following miR-23a-5p overexpression. The TNF-α-induced decreases in MH7A cell apoptosis were also reversed following miR-23a-5p overexpression. Additionally, transfection with miR-23a-5p mimics significantly inhibited the activation of the TLR4/NF-κB signaling pathway in TNF-α-treated MH7A cells by targeting TLR4. Notably, TLR4 overexpression weakened the effects of miR-23a-5p mimic on cell proliferation, apoptosis, migration, inflammation and the TLR4/NF-κB signaling pathway in TNF-α-induced MH7A cells. In conclusion, the findings of the present study indicated that the miR-23a-5p/TLR4/NF-κB axis may serve as a promising target for RA diagnosis and treatment.

TGF-ß1 +869T/C (rs1982073) gene polymorphism and susceptibility to rheumatoid arthritis: Updated systematic review and meta-analysis.

Rheumatoid arthritis (RA) is a complex autoimmune disease that affects about 1% of the world's population. The conclusions about the relationship between TGF gene polymorphism and the risk of RA are still inconsistent. Therefore, we performed a meta-analysis to re-evaluate the relationship between TGF-ß1 T869C gene polymorphism and the risk of rheumatoid arthritis. METHOD: We performed a systematic electronic search in PubMed, Embase, Elsevier, Web of Science, Cochrane Library, Medline and China National Knowledge Infrastructure database (up to August 2020). In the subgroup analysis, we divide the research into three groups: Asian, European and Mediterranean, The combined OR and 95%CI of the five models (allele model, homozygous model, heterozygous model, dominant model, recessive model) were calculated, respectively. RESULTS: 15 case-control studies (14 articles) were involved in this meta-analysis, including 2103 cases and 2143 healthy controls. In the overall analysis, it showed that there may be an significant association between TGF-ß1+869T/C polymorphism and RA sensitivity (allele model, T vs. C: OR=1.444, 95% CI=1.171-1.782, P=0.001; homozygous model, TT vs. CC: OR=1.910, 95% CI=1.322-2.761, P=0.001; heterozygous model, CT vs. CC: OR=1.558, 95% CI=1.179-2.059,P=0.002; dominant model, TT+CT vs. CC: OR= 1.742, 95% CI=1.303-2.329, P=0.001; recessive model, TT vs. CT+CC: OR=1.400, 95% CI= 1.058-1.852, P=0.018).However, the results of ethnic subgroup analysis indicated that rs1982073 was not associated with RA risk in Europeans(allele model, T vs. C: OR=0.993, 95% CI=0.849-1.162, P=0.931, I2 <0.1%, P>0.1). CONCLUSION: In summary, our meta-analysis showed that the rs1982073 T allele does not increase RA susceptibility in Europeans.

HDAC1 potentiates CD4 + T cell activation by inhibiting miR-124 and promoting IRF1 in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease leading to considerable morbidity worldwide, which can be developed from a breakdown in immunological tolerance, resulting in T cell hyperactivation. T cell hyperactivation has been implicated in the tissue damage associated with many diseases. Although many researchers have identified the involvement of T-cell receptor-associated signaling molecules in T-cell activation, the mechanisms underlying this process are yet to be elaborated. In the current study, we set out to reveal a novel transcriptional mechanism required for CD4 + T cell immunoactivity involved in SLE. First of all, miR-124 was experimentally determined to be under-expressed in peripheral blood samples of SLE patients relative to healthy individuals. We further isolated CD4 + T cells from the peripheral blood samples of SLE patients and healthy individuals, and found that miR-124 was poorly expressed in peripheral blood-derived CD4 + T cells of SLE patients. Subsequent experiments demonstrated that re-expression of miR-124 inhibited the immunoactivity of CD4 + T cells from SLE patients, which was achieved through the down-regulation of IRF1 since dual-luciferase reporter gene assay findings indicated that miR-124 could target IRF1. In addition, HDAC1 was found to be enriched at the miR-124 promoter resulting in inhibition of miR-124 expression, thereby promoting the immunoactivity of CD4 + T cells. In conclusion, we identify that as a stimulator of CD4 + T cell immunoactivity, HDAC1 may be implicated in the immunopathology of SLE. The study will open up new avenues to explore future immunotherapy strategies for SLE.

Regulation of Toll-like receptor-mediated inflammatory response by microRNA-152-3p-mediated demethylation of MyD88 in systemic lupus erythematosus.

OBJECTIVE: microRNAs (miRNAs) play critical roles in embryogenesis, cell differentiation and the pathogenesis of several human diseases, including systemic lupus erythematosus (SLE). Toll-like receptors (TLRs) are also known to exert crucial functions in the immune response activation occurring in the pathogenesis of autoimmune diseases like SLE. Herein, the current study aimed to explore the potential role of miR-152-3p in TLR-mediated inflammatory response in SLE. METHODS: We determined the miR-152-3p expression profiles in CD4+ T cells and peripheral blood mononuclear cells (PBMCs) harvested from patients with SLE and healthy controls, and analyzed the correlation between miR-152-3p expression and clinicopathological parameters. CD70 and CD40L expression patterns in CD4+ T cells were assessed by RT-qPCR and flow cytometry. ChIP was adopted to determine the enrichment of DNA methyltransferase 1 (DNMT1) in the promoter region of myeloid differentiation factor 88 (MyD88). RESULTS: The obtained findings revealed that miR-152-3p was highly-expressed in CD4+ T cells and PBMCs of patients with SLE, and this high expression was associated with facial erythema, joint pain, double-stranded DNA, and IgG antibody. DNMT1 could be enriched in the MyD88 promoter, and miR-152-3p inhibited the methylation of MyD88 by targeting DNMT1. We also found that silencing miR-152-3p inhibited MyD88 expression not only to repress the autoreactivity of CD4+ T cells and but also to restrain their cellular inflammation, which were also validated in vivo. CONCLUSION: Our study suggests that miR-152-3p promotes TLR-mediated inflammatory response in CD4+ T cells by regulating the DNMT1/MyD88 signaling pathway, which highlights novel anti-inflammatory target for SLE treatment.

Top 100 Cited Articles on Osteoarthritis from 1990 to 2020.

Objectives: The purpose of this study was to identify and analyze the 100 top-cited articles in the field of osteoarthritis (OA) from 1990 to 2020. Methods: We used the Web of Science to retrieve the articles related to OA. Then we selected 100 target articles and manually collected their general information, including article title, author, year of publication, journal, type of article, and the number of citations. Results: The 100 top-cited articles were published in the period from 1990 to 2015. These articles have been cited 66,494 times in total, with the highest being 2382 times, the lowest being 433 times, the median number being 613, and a mean of 664.94 times. The 100 top-cited articles appeared in a total of 35 influential journals. The greatest number of articles in the top of 100 was published in Arthritis and Rheumatism. The authors of these articles came from 18 countries, led by the United States (n = 48), followed by the United Kingdom (n = 15). Among all the institutions, Boston University led the list with 10 articles. The most prevalent type of the study was review (n = 38) and clinical study (n = 38), followed by guideline (n = 12), basic science (n = 10) and other types. Conclusions: This study provided some insights on the literature development and citation of OA in the recent 30 years. Articles published in high-impact journals are more likely to be cited in the field of OA. As recent studies did not have enough time to accumulate the number of citations, the latest articles may not be included in the top 100 cited articles.

The risk of leukemia in patients with rheumatoid arthritis: a systematic review and meta-analysis.

OBJECTIVES: The relationship between rheumatoid arthritis (RA) and the risk of leukemia was still controversial. This study aimed to assess the risk of leukemia in patients with rheumatoid arthritis by systematic review and meta-analysis. METHODS: Relevant studies were identified by searching PubMed, Embase, Cochrane Library, and SinoMed up to December 2019. Random effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence interval. RESULTS: A total of 15 relevant studies that met the criteria were included. Compared with the general population, patients with RA showed an increased risk of leukemia (SIR = 1.51, 95% CI: 1.34-1.70). The statistical heterogeneity was moderate with an I2 of 55.5%. In subgroup analysis, the source of heterogeneity may be due to differences in sample size. Publication bias was not found in the Begg funnel plot and the Egger test. CONCLUSION: Our findings suggested that the risk of leukemia in RA was increased compared with the general population. Key points • This is the first systematic review and meta-analysis to assess the risk of leukemia in RA. • Our study suggested that the risk of leukemia in RA was increased compared with the general population. • This study indicated that the risk of leukemia in RA was higher in non-Asian populations.

Silencing long non-coding RNA NEAT1 attenuates rheumatoid arthritis via the MAPK/ERK signalling pathway by downregulating microRNA-129 and microRNA-204.

The participation of long noncoding RNAs (lncRNAs) and microRNAs (miRs) in the progression of rheumatoid arthritis (RA) is a key area of investigation. The current study aimed to investigate the action of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in fibroblast-like synoviocyte (FLS) proliferation and synovitis in RA. A rat model of RA was established. LncRNA NEAT1 expression in the synovial tissues of patients with RA and FLSs from the RA rat model was determined using RT-qPCR. Next, dual luciferase reporter gene assay was applied to investigate the relationship between miR-129/204 and mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase (ERK). A putative binding relationship between miR-204 and lncRNA NEAT1 was evaluated by RIP assay, and miR-129 promoter methylation was determined using MSP. After the expression of lncRNA NEAT1, miR-129 or miR-204 was altered in FLSs, the extent of ERK1/2 phosphorylation was assessed. In addition, FLS synovitis and proliferation were determined by ELISA and EdU assay, respectively. In RA rats, lncRNA NEAT1 was silenced and miR-129/miR-204 was overexpressed to explore their roles in vivo. LncRNA NEAT1 was upregulated, while miR-129 and miR-204 were downregulated in RA synovial tissues and FLSs. MAPK1 was target gene of both miR-129 and miR-204. LncRNA NEAT1 bound to miR-204 and promoted miR-129 promoter methylation. Silencing lncRNA NEAT1 or overexpressing miR-129/miR-204 enhanced miR-129/miR-204 expression, but reduced the extent of ERK1/2 phosphorylation, proliferation of FLSs, and synovitis in RA. Collectively, silencing lncRNA NEAT1 promoted miR-129 and miR-204 to inhibit the MAPK/ERK signalling pathway, reducing FLS synovitis in RA.Abbreviations: ACR: American College of Rheumatology; ELISA: Enzyme-linked immunosorbent assay; ERK: extracellular signal-regulated kinase; FLS: fibroblast-like synoviocyte; GADPH: glyceraldehyde-3-phosphate dehydrogenase; HRP: horseradish peroxidase; IFA: Incomplete Freund's Adjuvant; lncRNAs: long noncoding RNAs; MSP: Methylation-specific PCR; NC: negative control; NEAT1: nuclear paraspeckle assembly transcript 1; OD: optical density; RA: rheumatoid arthritis; RIPA: Radio Immunoprecipitation Assay; RLU: relative light units; RT-qPCR: reverse transcription quantitative polymerase chain reaction; UTR: untranslated region.