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Uric acid is a powerful antioxidant. However, its elevated levels in association with cardiovascular diseases predispose individuals to cognitive impairment. Uric acid’s effects on cognition may be related to its concentration and exposure period. We aimed to explore the effects of long-term elevated serum uric acid on cognitive function and hippocampus. Rats were randomly divided into four groups: NC, M1, M2 and M3 groups. Hyperuricemia was established in rats at week 6 and maintained until week 48 in groups M1, M2 and M3. The rats’ spatial learning and memory abilities were assessed by the Morris Water Maze test at weeks 0, 6, 16, 32, and 48. After week 48, we observed pathological changes in right hippocampal CA1 and CA3 regions, and measured levels of oxidative stress, inflammatory cytokines, and β-amyloid peptide of left hippocampus. Starting from week 6, the serum uric acid level of M3 group > M2 group, the serum uric acid level of M2 group > M1 group, and the serum uric acid level of M1 group > NC group. The rats in M3 and M2 groups had longer escape latencies, longer mean distances to the platform, more extensive pathological damage, stronger inflammation response, higher oxidative stress and β-amyloid peptide levels than those in NC group. No significant differences were observed between M1 and NC groups. In addition, we also found that oxidative stress significantly correlated with tumour necrosis factor-α and β-amyloid peptide. Long-term elevated serum uric acid was significantly associated with cognitive impairment risk. Oxidative stress, tumour necrosis factor-α and β-amyloid peptide may mediate the pathogenesis of the cognitive impairment induced by uric acid. The detrimental effect of elevated serum uric acid on cognitive function was probably expressed when the serum uric acid concentration reached a certain level.

IL‐38 is a newly identified cytokine that belongs to the IL‐1 family. In our previous study, we found elevated plasma levels of IL‐38 in patients with systemic lupus erythematosus (SLE). However, the clear relationship of IL‐38 expression in plasma, peripheral blood mononuclear cells (PBMCs) and clinical and laboratory features needs elucidation. Additionally, we evaluated the possible role of IL‐38 in regulating production of inflammatory cytokines in PBMCs in vitro. A pristane‐induced murine lupus model was used to further demonstrate the effects of IL‐38 on cytokines in vivo and discuss the significance of IL‐38 in lupus development. The results showed that mRNA expression of IL‐38 in PBMCs of patients with SLE was elevated compared with volunteers, and expression of IL‐38 in both plasma and PBMCs was strongly related to clinical features, such as haematuria and proteinuria, and correlated with a SLEDAI score. Plasma levels of TNF‐α, IL‐1β, IL‐6 and IL‐23 were elevated in patients with SLE and were related to plasma levels of IL‐38. In vitro, PBMCs of patients with SLE stimulated with IL‐38 showed a decreased expression of the four inflammatory cytokines compared with PBMCs of patients without treatment. Interestingly, IL‐38 administration in lupus mice significantly reduced the development of lupus, such as reduced proteinuria, improved histological examinations of the kidneys and down‐regulated inflammatory cytokines. In conclusion, IL‐38 may suppress synthesis of pro‐inflammatory cytokines and therefore regulate lupus pathogenesis.

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.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.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 IOur 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.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder. MASP2 is a mediator that plays an important role in complement system. As dysregulation of the complement system has been demonstrated to correlate with SLE pathogenesis, the role of MASP2 in lupus has not been widely discussed. In the present study, serum levels of MASP2 were evaluated in 61 lupus patients and 98 healthy controls by training cohort, and then a validation cohort including 100 lupus, 100 rheumatoid arthritis, 100 osteoarthritis, 100 gout, 44 Sjogren's syndrome, 41 ankylosing spondylitis patients confirmed the findings. Receiver operating characteristic (ROC) curve analysis determined the discriminatory capacity for serum MASP2. PCR methods tested the association of MASP2 gene polymorphisms (rs7548659, rs17409276, rs2273346, rs1782455 and rs6695096) and SLE risk. Impact of polymorphism on MASP2 serum levels was evaluated as well. Results showed that serum levels of MASP2 were significantly higher in lupus patients and correlated with some clinical, laboratory characteristics in the training cohort, and were much higher as compared to that in different rheumatic diseases patients in the validation cohort. Serum MASP2 showed a good diagnostic ability for lupus. Genotype frequencies and allele frequency of polymorphisms rs7548659, rs2273346 were strongly related to SLE risk, and genotypes of rs17409276, rs1782455, rs76695096 were significantly correlated with lupus genetic susceptibility. Interestingly, patients carrying GA genotype of rs17409276, TT, TC genotype of rs6695096 showed higher levels of serum MASP2. The findings suggested that MASP2 may be a potential disease marker for lupus, and correlate with SLE pathogenesis.

Association of signal transducer and activator of transcription 4 (STAT4) gene rs7574865, rs10168266 polymorphisms with systemic lupus erythematosus (SLE) risk remains unclear. A meta-analysis was conducted on the correlation between rs7574865, rs10168266 polymorphisms and SLE. Twenty-six studies were recruited in our study (17,389 patients and 29,273 controls). For rs7574865, results showed significant associations between T allele and SLE susceptibility in overall population, Asians and Europeans (OR=1.557, 95%CI: 1.505-1.611, P0.001; OR=1.557, 95%CI: 1.498-1.661, P0.001; OR=1.548, 95%CI: 1.474-1.625, P0.001). Significant associations of genotypes TT, GT, TT+TG and SLE risk were observed in general subjects, Asians and Europeans (all P0.001). Regarding rs10168266, increased T allele frequencies were detected in overall SLE cases and those from Asian origin (OR=1.532, 95%CI: 1.440-1.631, P0.001; OR=1.575, 95%CI: 1.445-1.717, P0.001). The overall data showed that TT genotype, CT genotype and TT+CT genotype were significantly correlated with SLE (all P0.001). In conclusion, the present study verified strong association of STAT4 gene rs7574865, rs10168266 polymorphisms and SLE susceptibility.

Interleukin‐29 (IL‐29) is a newly discovered member of type III interferon. It mediates signal transduction via binding to its receptor complex and activates downstream signalling pathways, and therefore induces the generation of inflammatory components. Recent studies reported that expression of IL‐29 is dysregulated in inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Sjögren's syndrome, psoriasis and systemic sclerosis. Furthermore, functional analysis revealed that IL‐29 may involve in the pathogenesis of the inflammatory autoimmune disorders. In this review, we will systematically review the current knowledge about IL‐29. The information collected revealed the regulatory role of IL‐29 and may give important implications for its potential in clinical treatment.

This study evaluated expression of circRNA in primary Sjögren's syndrome (pSS) patients so as to find novel biomarkers for pSS screening and discussed possible role of circRNA in pSS. We also evaluated expression profile of circRNA in systemic lupus erythematosus (SLE) patients.Microarray analysis detected circRNA expression in PBMCs from five paired pSS, SLE patients, and controls. Then, differentially expressed circRNAs were validated in 30 pSS patients as compared to 30 SLE patients, healthy controls. CircRNAs interacting with miRNAs were discussed by Arraystar's homemade miRNA target prediction software. ROC analysis assessed the diagnostic value.We identified 234 differentially expressed circRNAs in pSS patients and verified five selected circRNAs (including hsa_circRNA_001264, hsa_circRNA_104121, hsa_circRNA_045355, hsa_circRNA_103461, hsa_circRNA_105034). Expression of hsa_circRNA_001264, hsa_circRNA_104121, and hsa_circRNA_045355 was strongly related to some clinical, laboratory parameters, and disease activity index in pSS patients. ROC analysis indicated potential diagnostic ability for the three circRNAs in pSS patients. One hundred and forty-eight circRNAs were differently expressed between lupus patients and controls.This study provides evidence that hsa_circRNA_001264, hsa_circRNA_104121, and hsa_circRNA_045355 might be biomarkers for pSS, correlate with pSS etiology.Key Points• Many circRNAs were dysregulated in pSS patients.• Differentially expressed circRNAs correlated with pSS clinical, laboratory features.• CircRNAs may be biomarkers for pSS.

Interleukin-34 (IL-34) shares a common receptor with macrophage colony-stimulating factor (M-CSF), and can bind to CSF-1R, induces lymphocytes differentiation, proliferation, and regulates the synthesis of inflammatory components. Recent findings reported aberrant expression of IL-34 in several autoimmune disorders, such as lupus, arthritis, systemic sclerosis, inflammatory bowel diseases. The functional analysis further demonstrated that IL-34 may perform significantly in these inflammatory autoimmune disorders. IL-34 might consider as a biomarker for these diseases. I hope this collection of the findings in this review will improve knowledge of the role of IL-34, and targeting IL-34 may give the potential for these autoimmune diseases.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with local, systemic inflammation, such as persistent synovial inflammation. Interaction of immune cells and inflammatory mediators results in amplification and perpetuation of inflammatory, remodelling process. This disease is characterized by joints swelling, redness, and arthralgia.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases. CD40 participates in inflammatory response, and promotes fibroblast proliferation, leading to occurrence and progression of SLE, RA. This study explores CD40 gene polymorphisms in SLE and RA patients from a Chinese Han population. Two hundred SLE patients, 340 RA patients, and 900 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood, and six polymorphisms of CD40 gene (rs3765456, rs1569723, rs73115010, rs13040307, rs1883832, and rs4810485) were detected by KASP method. Frequencies of rs1569723 genotypes AA, AC, AA+AC were significantly higher in RA patients as compared to those in healthy controls (P = 0.049, P = 0.024, P = 0.022). Frequencies of genotypes CT, CC+CT of rs1883832, and GT, GG+GT of rs4810485 were significantly higher in RA patients as compared to those in healthy controls (P = 0.012, P = 0.018, P = 0.009, P = 0.015). RA patients carrying rs13040307 C allele and rs73115010 T allele showed increased number of swollen joints. Moreover, frequency of allele T of rs13040307 was lower in SLE patients with positive anti-dsDNA and hematuria as compared to that in patients without these parameters (P = 0.038, P = 0.045). There were increased frequencies of genotype TT, allele T for rs13040307 and lower frequencies of genotype TT, allele T for rs73115010 in lupus patients with myositis (all P

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. 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. 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

Interleukin-37 (IL-37) is an anti-inflammatory cytokine. In our former study, we found increased plasma IL-37 levels in systemic lupus erythematosus (SLE) patients. However, relationship between IL-37 levels and clinical laboratory characteristics of SLE patients has not been elucidated. In addition, association of

Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case–control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.

Interleukin (IL)-35 is the newest member of the IL-12 family. It is expressed in many immune cells and has been recognized as a novel inflammatory cytokine that may have bifunctional properties. Recent findings have indicated that the expression of IL-35 is abnormal in rheumatoid arthritis (RA) patients. However, the results were inconsistent. In this study, 400 RA patients were recruited to evaluate serum levels of IL-35 in a Chinese Han population by enzyme-linked immunosorbent assay. The association of IL-35 gene polymorphisms and RA genetic susceptibility was investigated in 400 RA patients and 612 healthy controls. The results showed that serum levels of IL-35 were elevated in 100 RA patients compared to 51 healthy controls, relating to disease activity and synovial fluid IL-35 expression in the training cohort. Another independent 300 RA patients and 369 other rheumatic disease patients (98 lupus, 95 osteoarthritis, 95 gout, 42 Sjogren's syndrome and 39 ankylosing spondylitis patients) confirmed that serum levels of IL-35 were elevated in RA patients, and serum IL-35 has good diagnostic ability for differentiating RA from the other rheumatic diseases. The genotyping of 10 IL-35 polymorphisms, including rs2227314, rs2243115, rs2243123, rs2243131, rs568408, rs583911, rs428253, rs4740, rs9807813 and rs4905, revealed that rs2227314, rs2243131, rs9807813, and rs583911 were correlated with RA risk. Different genotypes (rs2227314, rs583911, and rs9807813) exhibited different expression of IL-35. These findings demonstrate that serum levels of IL-35 are increased in RA patients and that IL-35 polymorphisms are correlated with RA risk.

This study aimed to discuss association between serum Angiopoietin2 (Ang2) levels, Ang2 gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility. It was carried out by 235 SLE, 342 other inflammatory autoimmune diseases patients and 380 healthy individuals. Serum Ang2 levels was examinated by ELISA, and Ang2 rs12674822, rs1823375, rs1868554, rs2442598, rs3739390 and rs734701 polymorphisms were genotyped using KASP. Increased Ang2 concentrations in SLE patients were observed compared with healthy controls and patients with other inflammatory autoimmune diseases. For allelic contrast, except for rs1823375 (P = 0.058) and rs2442598 (P = 0.523), frequencies of alleles for other polymorphisms were significantly different between SLE patients and controls. Genotypes for rs12674822 (TT), rs1868554 (TT, TA and TT+TA), rs734701 (TT) were negatively correlated with SLE susceptibility (OR = 0.564 for rs12674822; OR = 0.572, OR = 0.625, OR = 0.607 for rs1868554; OR = 0.580 for rs734701). Patients carrying rs1868554 T allele and rs3739390 G allele were more likely to develop hematuria (P = 0.039; P = 0.003). The G allele frequencies of rs12674822 and rs2442598 were higher in SLE patients with proteinuria (P = 0.043; P = 0.043). GC genotype frequency of rs3739390 was higher in patients with ds-DNA (+) (P = 0.024). In summary, SLE had increased serum Ang2, which may be a potential biomarker, and the polymorphisms correlated with SLE.

OBJECTIVES: Mannose binding lectin (MBL) gene single nucleotide polymorphisms have been associated with systemic lupus erythematosus (SLE) risk with inconsistent results. This study aimed to explore whether MBL2 A\B, A\C, A\D, A\O, L\H and Y\X polymorphisms affected SLE susceptibility. METHODS: A meta-analysis was performed on 20 studies, containing allelic contrast, additive, dominant and recessive models. Odds ratio (OR) was calculated to reflect the effect of association. RESULTS: A total of 64 pooled comparisons were conducted, including 7194 SLE patients and 7401 healthy controls. The meta-analysis inducted a significant association between allele B and SLE (OR = 0.766, 95% CI = 0.681-0.862, P

Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis. In addition, functional analysis suggested that IL-35 is critical in the onset and development of these diseases. Therefore, the present study will systematically review what had been occurred regarding IL-35 in inflammatory autoimmune disease. The information collected will help to understand the biologic role of IL-35 in immune cells, and give information about the therapeutic potential of IL-35 in these diseases.

Aim This study aims to discuss risk factors associated with cervical spine involvement (CSI) in patients with rheumatoid arthritis (RA). Methods A literature search was performed in Medline, EMBASE, Web of Science and CBMdisc databases for potential studies published before October 2016. The clinical and laboratory data were extracted, and a meta-analysis was performed to evaluate the risk factors for CSI in RA patients. Results Twelve studies involving a total of 2750 cases with RA and 733 CSI (26.65%) were eligible and included in this meta-analysis. The results showed that risk factors for CSI were female (odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.079–1.74), positive rheumatoid factor (RF) (OR = 1.351, 95% CI: 1.084–1.683), long-term corticosteroids treatment (OR = 2.208, 95% CI: 1.732–2.815), erosion in hands or feet (OR = 2.559, 95% CI: 1.985–3.299), age (weighted mean difference [WMD] = −2.464 years, 95% CI: −3.688 to −1.240), RA duration (WMD = 1.495 years, 95% CI: 0.870–2.121), erythrocyte sedimentation rate (ESR) level (standard mean difference [SMD] = 0.288, 95% CI: 0.161–0.41), C-reactive protein (CRP) level (SMD = 0.288, 95% CI: 0.161–0.415), Disease Activity Score of 28 joints (SMD = 0.5, 95% CI: 0.303–0.697). Conclusion The significant risk factors for CSI in RA were female gender, positive RF, long-term corticosteroids treatment, peripheral joints erosions, younger age, long RA duration, markers of higher disease activity (ESR, CRP and Disease Activity Score).

Interleukin (IL)-36 is a member of the IL-1 superfamily and includes three agonists (IL-36α, IL-36β, and IL-36γ) and an antagonist (IL-36Ra). IL-36 agonists bind to heterodimeric receptor complexes. Then, the heterotrimer complexes signal via intracellular functional domains, binding to downstream signaling proteins and inducing inflammatory responses. In this review, we summarized the current knowledge about the biological role of IL-36 and its correlation with systemic inflammatory diseases. The information collected will help to increase the understanding of the potential of IL-36 and may give clues for developing novel therapeutic strategies.

Innate immune signaling plays an important role in inflammation, and dysregulation of signaling components within this pathway has been focused as a critical mediator in initiation, progression of inflammatory autoimmune diseases. Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the immune cells, detecting pathogen associated molecular patterns, initiating signal transduction, by which interleukin-1 receptor-associated kinase (IRAK) family mediates activating signal from TLRs and interleukin-1 receptor. The family comprises of four members, IRAK1, IRAK2, IRAK-M, IRAK4. The family members have a role in either positive or negative regulation of innate immunity, adaptive immunity and inflammation. Accumulated evidence proves that IRAK performs significantly in the pathogenesis of inflammatory autoimmune disorders. On the one hand, both patients and animal modes reported abnormal expression of the family members. On the other hand, functional study in vivo and in vitro demonstrated that the members are implicated in the development of the diseases. Interestingly, IRAK inhibition has potential therapeutic benefits. In this review, we focus on the family, review the physiological roles in different immune cells, and summarize emerging data for highlighting the importance of them in inflammatory autoimmunity.

Galectin family is a group of glycan-binding proteins. Members in this family are expressed in different tissues, immune or non-immune cells. These molecules are important regulators in innate and adaptive immune response, performing significantly in a broad range of cellular and pathophysiological functions, such as cell proliferation, adhesion, migration, and invasion. Findings have shown that expression of galectins is abnormal in many inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, sjögren's syndrome, systemic sclerosis. Galectins also function as intracellular and extracellular disease regulators mainly through the binding of their carbohydrate recognition domain to glycoconjugates. Here, we review the state-of-the-art of the role that different galectin family members play in immune cells, contributing to the complex inflammatory diseases. Hopefully collection of the information will provide a preliminary theoretical basis for the exploration of new targets for treatment of the disorders.

Background Interleukin-2 inducible T-cell kinase (ITK) is expressed in T cells, and plays an important role in autoimmune inflammatory diseases through regulating the balance of Th17/Treg. However, its role in human systemic lupus erythematosus (SLE) remains unclear. The present study aims to measure the activation status of ITK in T cells from SLE patients and healthy controls, and identify its possible correlation to disease severity. We also discuss the serum levels of Th17, Treg related cytokines including IL-17, IL-21, IL-22, IL-10, analyzing correlation between ITK and Th17/Treg related cytokines. Methods Peripheral blood samples were drawn from 42 patients with SLE and 43 healthy blood donors, and the phosphorylation of ITK protein was studied in T cells using flow cytometry. In addition, serum levels of Th17/Treg related cytokines were studied with enzyme-linked immunosorbent assay (ELISA). Results Percentages of CD4 + pITK + T cells, CD8 + pITK + T cells were higher in SLE patients compared with controls, and were positively related to disease activity, some clinical and laboratory parameters. Percentages of CD4 + pITK + T cells, CD8 + pITK + T cells were more prominent in active SLE patients compared with less active patients. Serum levels of Th17 and Treg related cytokines were higher in patients compared with controls. CD4 + pITK + T cells were related to levels of IL-17, IL-21. Conclusion These data indicate that increased ITK expression could act as a disease activity marker and as a risk factor for involvement in SLE, but it still needs further study to confirm.

Systemic lupus erythematosis (SLE) is an inflammatory autoimmune disease with multiple organs, systems damage. To date, the clear pathogenesis of SLE has not been fully clarified. However, genetics, environmental factors and dysregulated immunity were related to onset of this complex disease.

Osteoarthritis (OA) is a chronic degenerative joint disease, characterized by destruction of articular cartilage. This disease can markedly reduce quality of life of OA patients, leading to increased physical and psychological damage, for instance, pain and disability, and causing a serious impact on social economy.

Angiogenesis is defined as the growth of new capillaries sprouting from pre-existing vasculature. Pathological angiogenesis signals can lead to dysregulated development of new vessels. Inflammation is accompanied by pathological angiogenesis. During an inflammatory process, newly formed blood vessels provide oxygen and nutrients to the inflamed tissue, facilitating the transport of inflammatory cells. Therefore, angiogenesis is closely related to pathogenesis of inflammatory autoimmune diseases. As a member of the angiopoietin family, Angiopoietin-2 (Ang-2) plays an irreplaceable role in angiogenesis. This review will narrate the expression of Ang-2 and its role in inflammatory autoimmune diseases. Collecting this information may improve the acquaintance of Ang-2 and provide a theoretical foundation for clinical trials and drug development in the future.

BACKGROUND This study aimed to discuss the relationship between interferon regulatory factor (IRF)5 gene rs2004640 T/G polymorphism and systemic lupus erythematosus (SLE) susceptibility. METHODS A meta-analysis was calculated on the association between rs2004640 polymorphism and SLE by allelic contrast (T vs G), additive model (TT vs GG), recessive model (TT vs TG + GG) and dominant model (TT + TG vs GG). RESULTS A total of 28 comparisons were identified, including 11 228 SLE cases and 14 374 controls. Meta-analysis revealed a significant association between allele T and SLE in overall populations (odds ratio [OR] = 1.393, 95% CI: 1.276-1.522, P

AIM This study aims to discuss plasma and messenger RNA (mRNA) levels of interleukin (IL)-37 in rheumatoid arthritis (RA) patients and evaluate the potential of plasma IL-37 as a biomarker for RA. METHOD Plasma IL-37 levels and IL-37 mRNA relative concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). We discussed the association of IL-37 levels and clinical, laboratory parameters in RA patients in a training cohort. Plasma IL-37 levels were tested for discriminatory capacity by receiver operating characteristic (ROC) curve analysis. We then validated plasma IL-37 expression in a cohort of 598 patients (230 RA, 107 systemic lupus erythematosus [SLE], 100 osteoarthritis [OA], 62 gout, 51 primary Sjogren's syndrome [pSS], 48 ankylosing spondylitis [AS]). RESULTS Both plasma levels of IL-37 and mRNA levels of IL-37 were elevated in RA patients compared to those in healthy controls in the training cohort, and there was a good diagnostic ability to predict RA (area under the curve [AUC] = 0.97). Plasma IL-37 levels were significantly related to Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) (rs = 0.459, P

Previous studies have indicated that interleukin-38 (IL-38) is involved in rheumatoid arthritis (RA). The present study aims to assess plasma levels of IL-38 in RA and discuss the potential of IL-38 as a biomarker for RA. Protein concentrations of IL-38 were examined by enzyme-linked immunosorbent assay, and the mRNA level of IL-38 was tested by quantitative real-time polymerase chain reaction. Plasma IL-38 was first compared in a training cohort, including 130 RA patients and 53 healthy controls, given the optimal cutoff. Then, we validated the levels of IL-38 in a further cohort of 519 patients, including 250 with RA, 63 systemic lupus erythematosus, 62 primary Sjogren's syndrome, 51 gout, 63 osteoarthritis, and 30 psoriatic arthritis, as well as 60 healthy controls. To further discuss the changes in IL-38 after treatment and the relationship with disease activity, we tested IL-38 expression in RA patients from the training cohort under follow-up. In the training cohort, plasma levels of IL-38 were higher in RA patients compared with healthy controls (681.00 [234.45-826.47] versus 152.04 [70.06-246.80] pg/mL, P < 0.001). The IL-38 mRNA level was elevated in RA patients as compared with healthy controls (P < 0.001). Expression of IL-38 was significantly higher in RA patients compared with that in non-RA patients in the validation cohort (all P < 0.001). Treatment significantly reduced IL-38 expression. IL-38 expression was related to parameters of inflammation both at baseline and in the follow-up studies. The area under the curve (AUC) of the receiver-operating characteristic curve showed that IL-38 may be a potential biomarker for RA. At the optimal cutoff value of 341.90 pg/mL, the sensitivity, specificity, and AUC were 72.30%, 90.60%, and 0.840, respectively, in the training cohort. Similar results were noted in the validation cohort. In conclusion, IL-38 expression correlated with RA disease activity, and plasma IL-38 might be a promising diagnostic biomarker for RA.

Interleukin (IL)-38 is the newest member of the IL-1 family. It can bind to several receptors, regulate the generation, function of inflammatory cytokines through the downstream signaling pathways. IL-38 is expressed in several tissues, such as placenta, heart, and brain. It is involved in a wide variety of diseases, including chronic inflammatory diseases. In this review, we discuss the expression and biological functions of IL-38, especially the role in rheumatic autoimmune diseases. Collection of the information may improve the understanding of IL-38, and may give potential for theoretical basis for clinical trials and drug development in the future.

Autoimmune diseases are characterized by the impaired function and the destruction of tissues that are caused by an immune response in which aberrant antibodies are generated and attack the body's own cells and tissues. Interleukin (IL) -37, a new member of the IL-1 family, broadly reduces innate inflammation as well as acquired immune responses. Recently, studies have shown that expression of IL-37 was abnormal in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, Graves' disease (GD). In addition, functional analysis indicated that IL-37 is negatively involved in the development and pathogenesis of these autoimmune disorders. The strong association of this cytokine with autoimmune diseases promotes us to systematically review what had been published recently on the crucial nature of IL-37 in relation to autoimmune diseases gaining attention for its regulatory capability in these autoimmune disorders.

Systemic lupus erythematosus (SLE) is an autoimmune disease. The friend leukemia insertion site 1 (Fli-1) belongs to the Ets family of transcription factors. Recent findings suggested that expression of Fli-1 was abnormal in SLE patients and lupus mice. In addition, functional analysis indicated that Fli-1 plays a key role in the development of this complex autoimmune disorder. Here, we review the updated evidence indicating the roles of Fli-1 in autoimmune lupus. Hopefully, the information obtained may result in a better understanding of the pathogenesis of the systemic autoimmune disease.

Background and Aims Studies investigating the association between the peptidylarginine deiminase 4 (PADI4) gene polymorphisms and rheumatoid arthritis (RA) reported conflicting results. The aim of this meta-analysis was to assess the association between PADI4 gene polymorphisms and RA. Methods A systematic literature search was conducted to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Results A total of 34 studies from 28 articles involving 19859 patients with RA and 25771 healthy controls were included. Significant association of PADI4–94G/A polymorphism and RA was observed (OR = 0.891, 95% CI = 0.833–0.954, p = 0.001) in the overall study population and in the Asian populations (OR = 0.824, 95% CI = 0.759–0.894, p = 0.000) respectively. For the –92C/G polymorphism, a significant association was observed (OR = 1.481, 95% CI = 1.166–1.882, p = 0.001) in Africans. For the –90C/T polymorphism, a significant association was observed (OR = 0.576, 95% CI = 0.381–0.872, p = 0.009) in the Latin American population. The pooled estimates for the other polymorphisms were not statistically significantly associated with RA (PADI4–104C/T, –89A/G, –96T/C). Conclusions This meta-analysis demonstrates that PADI4–94G/A polymorphism is associated with susceptibility to RA in the overall population and in the Asian population. The PADI4 –92C/G polymorphism confers susceptibility to RA in Africans and the PADI4–90C/T polymorphism was associated with RA in the Latin American population.

The aim of this study was to determine whether caspase recruitment domain-containing protein 8 (CARD8) rs2043211 polymorphism was associated with susceptibility to inflammatory bowel disease (IBD).Relevant studies were searched using PubMed and Embase up to February 2014. A meta-analysis was conducted on the association between rs2043211 polymorphism and IBD using: (1) allele contrast, (2) the dominant model, (3) the recessive model, and (4) homozygote contrast. The pooled estimated of risk was obtained by random-effects model or fixed-effects model. Publication bias was assessed by Egger's test.Eight relevant articles with a total of 10 534 IBD patients [6785 Crohn's disease (CD), 3713 ulcerative colitis (UC) and 36 indeterminate colitis (IC)] and 6755 healthy controls were included in the meta-analysis, which consisted of 12 studies, 12 for CD, 10 for UC, 2 for IC. There was no significant association between rs2043211 polymorphism and IBD, CD, and IC in overall population. However, stratified meta-analysis by ethnicity showed significant association between rs2043211 polymorphism and CD in the European population under the dominant model [odds ratio (OR) = 1.210, 95% confidence interval (CI) = 1.013-1.445, p = 0.036] and homozygote contrast (OR = 1.212, 95% CI = 1.005-1.461, p = 0.044).Our meta-analysis results indicated significant association between rs2043211 polymorphism and the susceptibility to CD under the dominant model and homozygote contrast in the European population.

With socioeconomic growth and cultural changes in China, the level of blood glucose may have changed in recent years. This study aims to detect the blood glucose distribution characteristics with a large size of health examination population. A total of 641,311 cases (360,259 males and 281,052 females) more than 18 years old during 2007 to 2015 were recruited from the Health Examination Center at West China hospital, Sichuan University. The percentage of cases with abnormal glucose level and the mean level of glucose were significantly increased since 2007 to 2015 overall. The percentage of cases with abnormal glucose level in males was significantly higher than that in females every year, and the percentage of cases with abnormal glucose level in aged population was higher than the young population. In addition, the mean level of glucose was higher in aged population with normal level of glucose than the young population with normal level of glucose, and the mean level of glucose was higher in males with normal level of glucose than the females with normal level of glucose. The population showed an increased level of blood glucose. Some preventive action may be adopted early and more attention can be paid to them.

Background The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism confers susceptibility to systemic lupus erythematosus (SLE)/lupus nephritis (LN). Methods A meta-analysis was conducted on the association between the ACE I/D polymorphism and SLE/LN (when available) using: (i) the allelic contrast; (ii) the recessive; (iii) the dominant; and (iv) the additive models. Results A total of 27 relevant comparisons meeting the inclusion criteria were identified, involving 2718 SLE patients and 3655 controls. Meta-analysis showed a significant association between SLE and the allele D in overall populations (odds ratio [OR] = 1.25, 95% CI: 1.07-1.48, P = 0.004). Stratification by ethnicity indicated a strong association between the allele D and SLE in Asians (OR = 1.36, 95% CI: 1.05-1.75, P = 0.019). Meta-analysis also showed a significant association between SLE and the DD genotype in overall populations (additive model) (OR = 1.38, 95% CI: 1.05-1.83, P = 0.022). In addition, we found significant associations between the recessive model and SLE in overall populations, Asians and Europeans (OR = 1.44, 95% CI: 1.11-1.88, P = 0.007; OR = 1.69, 95% CI: 1.07-2.68, P = 0.024; and OR = 1.31, 95% CI: 1.06-1.62, P = 0.013, respectively). With respect to the association between ACE I/D gene polymorphism and LN risk, there was no significant association in either the overall populations or subpopulations. Conclusion The present study might suggest that ACE I/D polymorphism may be a genetic molecular marker to predict SLE, while this polymorphism may not correlate with LN susceptibility.

The H19 (rs2839698, rs3741219) and HOTAIR (rs920778) polymorphisms were related to many kinds of cancers. However, these polymorphisms have been scarcely explored in different autoimmune diseases. Here, we aimed to examine the association of the polymorphisms with susceptibility to or protection against systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren’s syndrome (pSS) among Chinese Han patients. We conducted a case-control study including 800 patients (300 with SLE, 350 with RA, and 150 with pSS) and 350 healthy control individuals. The polymorphisms were specified from genomic DNA using TaqMan genotyping assay on a 7300 real-time reverse transcription polymerase chain reaction system. H19 rs2839698 was not associated with SLE susceptibility and was not associated with RA and pSS, respectively (P > 0.05). Similarly, we did not find significant differences of allele or genotype frequencies between SLE, RA, and pSS patients and healthy controls for H19 gene rs3741219 polymorphism (P > 0.05). In addition, no significant evidence was detected for the relationship of HOTAIR rs920778 polymorphism with risk of these diseases. Our results suggested that H19 rs2839698, rs3741219, and HOTAIR rs920778 polymorphisms may not be involved in the genetic background of SLE, RA, and pSS in Chinese.

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.

Suppressor of cytokine signaling (SOCS) proteins are mainly induced by various cytokines and have been described as classical inhibitors of cytokine signaling. SOCS signaling is involved in the regulation of immune cells, and recent findings suggest that SOCS proteins, especially SOCS1 and SOCS3, are often dysregulated in a wide variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, psoriasis, and multiple sclerosis. Recent studies suggest that SOCS signaling could be therapeutically targeted in various autoimmune diseases. In this review, we discuss recent studies on the role of SOCS proteins in the development and pathogenesis of autoimmune diseases, as well as their clinical implications.

Stigma is a common problem among people living with HIV/AIDS (PLWHA). However, little is known about HIV/AIDS-related stigma in older PLWHA over the age of 50. This study described the stigma of HIV/AIDS and its factors based on 120 PLWHA aged 50 or older in an area of high HIV prevalence in south rural China. Each participant completed a face-to-face questionnaire that collected information on demographic characteristics, AIDS-related events and experience of HIV/AIDS-related stigma. Finally, only 18.1% reported experiencing external stigma compared with 64.3% feeling internal stigma. Regression analysis indicated that social support and health status were the two variables that were significantly predictive of both external and internal stigma. Whatever, the more support were received from family members by PLWHA, the less external stigma was perceived. Negative marital situation was also related to external stigma. Reducing HIV/AIDS stigma requires a supportive environment, positive attitude and correct knowledge of AIDS. Health workers and policy makers should take practical approaches to reduce prejudice.

Health examination is an important method for early detection of people with different risk of stroke. This study estimates the risk of stroke and identify risk factors for people who underwent health examinations at the Health Examination Center at West China Hospital, Sichuan University from July 2014 to February 2018.A total of 31,464 people were recruited in this study and divided into 3 groups (low risk, moderate risk, and high risk) according to risk of stroke. We explored possible factors associated with the risk of stroke by using multivariable stepwise logistic regression analysis.Among the participants, 17,959 were at low risk, 11,825 were at moderate risk, and 1680 were at high risk. Age, smoking, alcohol consumption, body mass index, uric acid, diastolic pressure, systolic pressure, triglycerides, low-density lipoprotein cholesterol, glucose, and brachial-ankle pulse wave velocity (baPWV) were independent significant risk factors for stroke, whereas high-density lipoprotein cholesterol was an independent protective factor for stroke. Interestingly, with increasing age, the percentage of people at moderate or high risk of stroke was increased. The percentages of people at moderate and high risk of stroke were also increased with respect to the stages of baPWV.This study showed that >40% of the participants were at moderate or high risk of stroke, especially the older participants. Several factors were related to the risk of stroke, especially baPWV. Some preventive action may be adopted early, and more attention can be paid to the health examination population.

Systemic lupus erythematosus (SLE) is complex autoimmune disease which involves various facets of the immune system. Signaling transducers and activators of transcription 1 (STAT1) belongs to the family of STAT transcription factors that mediate various biological responses. Recently, studies in both experimental animal models of lupus and patients with SLE have revealed expression and activation of STAT1 is closely associated with the pathogenesis of SLE. Moreover, increased production of interferons (IFNs) and aberrant activation of IFNs signaling, which is mechanistically linked to increased level of STAT1, are crucial for the development of SLE. Therefore, we will focus on the association of STAT1 and SLE based on recent understandings to render more information about the mechanisms of STAT1 might perform in. Hopefully, the information obtained will lead to a better understanding of the development and pathogenesis of systemic autoimmune diseases, as well as its clinical implications and therapeutic potential.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. The clear pathogenesis of SLE has not been fully elucidated. Cytokine-mediated immunity has been showed to be involved in the pathogenesis of SLE. The aim of this study was to investigate serum levels of cytokines (IL-19, IL-24, IL-26, IL-31, IL-32, IL-36) in SLE patients, in comparison with normal controls in a Chinese population. A total of 65 patients with SLE and 65 healthy volunteers were recruited for the current study. All serum levels of cytokines were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not significantly different from the normal controls (all p > 0.05). Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not markedly different from the normal controls. However, functional research should be discussed in future studies to elucidate the roles of these cytokines in SLE.

The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the association of interleukin-1 (IL-1), IL-10 and tumor necrosis factor (TNF)-α polymorphisms with Behcet's disease (BD). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 4003 cases and 4748 controls in 19 eligible studies were included in the meta-analysis. We examined the relationship between seven single nucleotide polymorphisms (SNPs) in the above-mentioned three cytokine genes and susceptibility to BD. Meta-analysis indicated the association between the cytokine gene polymorphisms in all study subjects in the allelic model (TNF-α -308A/G: OR = 0.73, 95% CI: 0.61–0.88, P = 0.001; IL-10 -819C/T: OR = 0.72, 95% CI: 0.66–0.78, P