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Objectives: Thrombomodulin (TM) is closely related to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). However, current evidence on circulating TM levels in SLE patients is contradictory. We conducted this meta-analysis to more accurately assess circulating TM levels in patients with SLE and lupus nephritis (LN) and to analyze related influencing factors. Methods: Systematic search of relevant documents was conducted in PubMed, Embase, and The Cochrane Library databases (up to 28 February 2021). Studies on the comparison of circulating TM between SLE patients and controls were screened and evaluated for inclusion. Random-effects model analysis was applied to calculate the combined standardized mean difference (SMD) with a 95% confidence interval (CI). Heterogeneity was estimated by Q statistics and I2. Results: A total of 353 articles were identified, 14 provided adequate information for this study finally. The results illustrated that SLE patients had higher TM levels than healthy controls (SMD=0.38, 95% CI: 0.02 to 0.74, p=0.04). Circulating TM levels were increased in patients with active SLE compared to inactive SLE patients (SMD=1.12, 95% CI: 0.03 to 2.20, p=0.04). In addition, circulating TM levels of SLE patients with LN were higher than those without LN (SMD=4.55, 95% CI: 1.97 to 7.12, p=0.001). Conclusions: The circulating TM levels in SLE patients are enhanced. In addition, circulating TM levels may be practical in reflecting the disease activity and nephritis involvement of SLE patients.

Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/β-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role.PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA).Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients.RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.HINTERGRUND: Für Sclerostin, ein Regulator des Knochenstoffwechsels und der Gefäßkalzifizierung, der an der Regulierung des Wnt/β-Catenin-Signalwegs beteiligt ist, wurde nachgewiesen, dass es auch in der Pathogenese der rheumatoiden Arthritis (RA) eine Rolle spielt. Jedoch sind die aktuellen Ergebnisse in Bezug auf die Werte für zirkulierendes Sclerostin bei RA-Patienten umstritten. Ziel der vorliegende Studie war es, die Werte für zirkulierendes Sclerostin bei RA-Patienten zu untersuchen und dessen Rolle kurz zusammenzufassen.Die Datenbanken PubMed, EMBASE und der Cochrane Library wurden systematisch bis 27. Mai 2021 auf infrage kommende Artikel hin durchsucht. Nützliche Daten aus allen geeigneten Arbeiten wurden systematisch erfasst und mittels der Software Stata 12.0 analysiert (Stata Corp LP, College Station, TX, USA).In dieser aktualisierten Metaanalyse wurden 13 geeignete Studien mit 1030 Fällen und 561 normalen Kontrollen ausgewertet. Das Walddiagramm dieser Metaanalyse zeigte, dass RA-Patienten höhere Werte für Werte für zirkulierendes Sclerostin aufwiesen als die normalen Kontrollen (p 0,001; standardisierte mittlere Differenz, SMD: 0,916; 95%-Konfidenzintervall, 95%-KI: 0,235–1,597). Untergruppenanalysen ergaben, dass Alter, Region und Bestimmungsmethode mit dem Sclerostinwert bei RA-Patienten in Zusammenhang standen.Bei RA-Patienten fanden sich höhere Werte für zirkulierendes Sclerostin auf als bei normalen Kontrollen. Dieser Zusammenhang wurde durch die Faktoren Alter, Region und Bestimmungsmethode beeinflusst.

IntroductionSeveral published results have established variations in respect to plasma/serum macrophage migration inhibitory factor (MIF) levels and gene polymorphisms with systemic lupus erythematosus (SLE). This study gave a more concise estimation on the MIF levels for SLE patients and established the association between MIF polymorphisms and SLE.Material and methodsAll articles were searched from PubMed, Embase, Web of Science, Wan-Fang, Chinese Biological Medical Literature, and China National Knowledge Infrastructure up to 6th October 2017, with no language restriction. Pooled standard mean difference with 95% confidence interval was evaluated using random effect model. Thirteen articles were used for this meta-analysis, with 620 SLE patients and 779 healthy controls assessed for MIF levels, and 2,159 SLE patients and 2,574 healthy controls considered for MIF-173 C/G and MIF-794 CATT polymorphisms.ResultsThere was a significant higher MIF levels in SLE patients than in healthy controls (p = 0.004). The subgroup analysis showed Asians and ages < 30 had higher MIF levels in SLE patients than in healthy controls. It was evident that patients with systemic lupus erythematosus diseases activity index scores < 8 and ≥ 8, and disease duration for both year < 5 and ≥ 5 of SLE had higher MIF levels when compared to healthy controls. We found a significant association between SLE and MIF-173 C/G, but not MIF-794 CATT.ConclusionsThis study provided evidence of significant higher MIF levels in SLE patients and supported the association of MIF-173 C/G and SLE. However, we were not able to establish an association between MIF-794 CATT and SLE.

Background The existing evidence suggests that pre-existing diabetes may modify the association between heat and hospitalizations for acute myocardial infarction (AMI). Methods This study included patients who were hospitalized for AMI from 1 January 2005 to 31 December 2013 in Brisbane, Australia, and also included those who died within 2 months after discharge. A time-stratified case-crossover design with conditional logistic regression was used to quantify the associations of heat and cold with hospitalizations and post-discharge deaths due to AMI in patients with and without pre-existing diabetes. Stratified analyses were conducted to explore whether age, sex and suburb-level green space and suburb-level socio-economic status modified the temperature–AMI relationship. Heat and cold were defined as the temperature above/below which the odds of hospitalizations/deaths due to AMI started to increase significantly. Results There were 14 991 hospitalizations for AMI and 1811 died from AMI within 2 months after discharge during the study period. Significant association between heat and hospitalizations for AMI was observed only in those with pre-existing diabetes (odds ratio: 1.19, 95% confidence interval: 1.00–1.41) [heat (26.3°C) vs minimum morbidity temperature (22.2°C)]. Cold was associated with increased odds of hospitalizations for AMI in both diabetes and non-diabetes groups. Significant association between cold and post-discharge deaths from AMI was observed in both diabetes and non-diabetes groups. Conclusions Individuals with diabetes are more susceptible to hospitalizations due to AMI caused by heat and cold.

Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a contagious viral disease, and toll-like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (rs3775290, rs3775291, rs3775296, rs1879026, rs5743312, rs5743313, rs5743303, rs13126816 and rs3775292), TLR4 (rs4986790, rs4986791, rs2149356, rs11536889 and rs41426344), TLR7 (rs179009, rs179010, rs179016, rs3853839, rs2302267, rs1634323 and rs5741880) and TLR8 (rs3764880, rs2159377, rs2407992, rs5744080, rs3747414, rs3764879 and rs5744069) genes were selected. The study indicated that individuals with the GG genotype of TLR3 single nucleotide polymorphism (SNP) rs1879026 had a higher risk of developing severe cases (GG vs GT: OR=1.875, 95% CI, 1.183-2.971, P=0.007). Meanwhile, TLR3 rs3775290 CC genotype and C allele were associated with lower disease severity in females (CC vs CT: OR=0.350, 95% CI, 0.163-0.751, P=0.006; C vs T: OR=0.566, 95% CI, 0.332-0.965, P=0.036). TLR3 rs3775291 CC genotype showed 2.537 folds higher risk of developing severe cases in females (CC vs CT: OR=2.537, 95% CI, 1.108-5.806, P=0.026). Moreover, TLR3 rs1879026 GG genotype was found to be related to increased risk of severe cases in males (GG vs GT: OR=2.076, 95% CI, 1.144-3.768, P=0.016). The current findings show that the genetic variants of TLR3 rs1879026, rs3775290 and rs3775291 are associated with the severity of EV-A71-associated HFMD in the Chinese children population. This article is protected by copyright. All rights reserved.

Objective: Due to the inconsistent results of current studies on the association between urinary and blood vascular cell adhesion molecule-1 (VCAM-1) and systemic lupus erythematosus (SLE) disease activity, we conducted this study and analyzed its influencing factors. Methods: A literature search was conducted in PubMed, EMBASE, Web of Science, and Cochrane Library. Data were extracted from eligible studies to calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Cochrane Q test and I2 statistics were used to examine heterogeneity. The sources of heterogeneity were assessed through sensitivity analysis and subgroup analysis. Publication bias was evaluated by funnel plots and Egger's test. Results: A total of 15 studies met the inclusion criteria, including 473 active SLE patients and 674 inactive SLE patients. The random effects model was used for data analysis. In both urine and blood samples, VCAM- 1 level in active SLE patients was significantly higher than those in inactive SLE patients (urine: SMD: 0.769; 95% CI: 0.260-1.278; blood: SMD=0.655, 95% CI: 0.084-1.226). No publication bias was found in this study. Conclusion: Compared with inactive SLE patients, patients with active SLE have higher levels of VCAM-1 in both urine and blood. VCAM-1 may be a potential indicator of SLE disease activity.

Objectives Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE. Methods We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P Results The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels. Conclusion Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.

Objectives : To explore the associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid (GC) efficacy, anxiety, depression, and health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE) patients. Methods : All subjects were collected from the First and the Second Affiliated Hospital of Anhui Medical University in Hefei, China, during 2011 to 2015. In the case–control study, 541 SLE patients and 543 controls were recruited. In the follow-up study, 466 patients completed the 12-week follow-up and then were divided into GC-sensitive and GC-insensitive groups. Genotyping was determined using Multiplex SNaPshot technique. Data were analyzed using chi-square test and univariate and multivariate logistic regression analyses. Results : rs4713904, rs9368878, and rs7757037 of FKBP5 were associated with depression in SLE patients (rs4713904, PBH = 0.037; rs9368878, PBH = 0.001; rs7757037, PBH = 0.003). Moreover, rs4713904 was associated with GC efficacy in males with SLE (PBH = 0.011). The rs755658 of FKBP5 was associated with improvement in social function (PBH = 0.022) and mental component summary (PBH = 0.028). The rs4713907 of FKBP5 was related to improvement in total score of SF-36, bodily pain, and mental component summary score (all PBH = 0.018). Furthermore, the rs12582595 of FKBP4 was correlated with general health improvement (PBH = 0.033). No associations were seen between FKBP4/FKBP5 gene polymorphisms and SLE susceptibility and anxiety. Conclusions : FKBP5 gene polymorphisms may be associated with depression and GC efficacy of SLE patients. Meanwhile, the genetic polymorphisms of FKBP4 and FKBP5 genes may be associated with HRQOL improvement in SLE patients.Key Points• FKBP5 gene polymorphisms were associated with depression of SLE patients.• FKBP5 gene polymorphisms were associated with GC efficacy of SLE patients.• FKBP5 gene polymorphisms were associated with HRQOL improvement in SLE patients.• FKBP4 gene polymorphisms were associated with HRQOL improvement in SLE patients.

Published studies have shown contradictory results in the association of serum/plasma levels of homocysteine (HCY) with systemic lupus erythematosus (SLE). This study is to systematically evaluate the association of serum/plasma HCY levels in SLE. A search was done using PubMed, Embase, Web of Science, and ScienceDirect databases up to 7 April 2019. Thirty-six articles including 2919 SLE patients and 3120 healthy controls were finally included in this meta-analysis. The HCY levels were significantly higher in SLE patients than in healthy controls (P 0.001). The subgroup analysis revealed that Asian, African, Arab, Mixed, White and others as well as ages ( 35 and ≥ 35) had significant higher HCY levels in SLE patients than in the healthy controls. The study indicated that patients with disease activity index scores 8 (P 0.001) and ≥ 8 (P = 0.003) of SLE had significant higher HCY levels as compared with the healthy controls. It was also revealed that disease duration in SLE patients for 10 and ≥ 10 years (P 0.001) had significant higher HCY levels as compared with the healthy controls. A significant higher HCY level for body mass index ( 23 and ≥ 23) was found as well as measurement type in SLE patients than healthy controls. This meta-analysis demonstrated higher HCY levels in patients with SLE than healthy controls, suggesting a possible role of HCY in the disease.Key Points• Homocysteine (HCY) is closely related to the mechanisms of systemic lupus erythematosus (SLE).• This study reveals a significant correlation between HCY levels and the various indexes of disease activity.• This study reveals that medication may influence HCY levels in SLE.• This study also discovers that the subgroup analysis of all the factors influences the HCY levels in SLE patients.

BACKGROUND Hospitalizations in patients with systemic lupus erythematosus (SLE) have been reported from different regions in the world. This study aimed to evaluate the annual hospitalization rate, causes of hospitalization, and potential factors associated with frequency of hospitalization in Chinese patients. MATERIAL AND METHODS We performed an ambispective cohort study for hospitalized patients with SLE in a Chinese single center. Data on demographics, organ involvements, laboratory abnormities, clinical treatments, causes of hospitalization, and survival outcomes were recorded at the time of SLE diagnosis and during a follow-up period. Poisson regression models were created to identify the potential factors associated with frequency of hospitalization. RESULTS Of 526 patients with SLE, 242 patients (46%) had 1 or more admissions amounting to a total of 449 times during a median follow-up period of 4.73 years. The annual hospitalization rate was 18% and death occurred in 2.5% of total admissions. SLE flare, infection and pregnancy-related morbidity were the most common causes of hospitalization. Besides, the multivariate Poisson regression analysis revealed that decreased albumin, decreased renal function, and high disease damage were the risk factors for more frequency of hospitalization, whereas positive anti-SSA antibody and use of hydroxychloroquine were protective factors. CONCLUSIONS Nearly half of patients (46%) with SLE experience 1 or more hospitalizations, mainly due to SLE flare, infection, and pregnancy-related morbidity. Lupus patients with decreased albumin, decreased renal function, and high disease damage are more susceptible to have frequent hospitalization.

Aim: To derive a precise estimation on plasma/serum level of SOD, GPx, CAT and GSH levels in systemic lupus erythematosus (SLE) patients. Methods: A total of 36 articles from electronic databases were finally included with 1120 SLE patients and 1024 healthy controls considered for antioxidant levels. Results: The levels of CAT and GSH were significantly lower, while SOD and GPx levels were slightly lower in patients with SLE compared with healthy controls. Subgroup analysis indicated that Arabs, ages ≥40 and SLE diseases activity index

The indicators for measuring vitamin D are various, and 25-hydroxyvitamin D (25(OH)D) is considered as the optimal indicator of total vitamin D levels. In this study, we aim to deeply explore the 25(OH)D status in systemic lupus erythematosus (SLE) patients, and evaluate its relation to SLE risk and disease severity.Literature about 25(OH)D status and its associations with SLE were searched in Pubmed, Embase and Cochrane Library databases. Standardized mean difference (SMD), odds ratio (OR) and corresponding 95% confidence interval (95% CI) were illustrated by forest plots, and correlation coefficients (r) were combined by generic inverse variance method. Heterogeneity and publication bias were quantified by I-squared (INineteen articles were included into our meta-analysis. The overall results showed that compared with the healthy controls, the circulating 25(OH)D levels were significantly lower in SLE patients (pooled SMD = -1.63, 95% CI: -2.51 to -0.76). Subgroup analysis revealed that compared with the healthy controls, SLE patients of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≥ 10, Arab and European ethnicity, all 4 seasons, no vitamin D supplement, had significantly lower circulating 25(OH)D levels; no significant differences were observed in SLE patients of SLEDAI 10, mixed ethnicity, spring, summer, vitamin D supplement, respectively; no matter the changes of age, disease duration, and the therapy of corticosteroid or immunosuppressive or neither, circulating 25(OH)D levels were significantly reduced in SLE patients. The deficiency, insufficiency and sufficiency of vitamin D could significantly elevate, slightly decrease (not significantly), significantly decrease SLE risk, respectively (pooled OR = 4.37, 95% CI: 1.49 to 12.84; pooled OR = 0.52, 95% CI: 0.22 to 1.26; pooled OR = 0.31, 95% CI: 0.15 to 0.63). Circulating 25(OH)D levels were inversely associated with SLEDAI (pooled correlation coefficient = -0.50, 95% CI: -0.8278 to -0.1689).Compared with healthy controls, 25(OH)D levels are significantly lower in SLE patients, which is influenced by disease activity, ethnicity, seasons and vitamin D supplement; no matter the change of age, diseases duration and therapy of corticosteroid or immunosuppressive or neither, 25(OH)D levels are significantly decreased in SLE patients; the deficiency, insufficiency and sufficiency of vitamin D could significantly elevate, slightly decrease, and significantly decrease SLE risk, respectively; and 25(OH)D levels inversely correlate with SLEDAI.

This study aims to investigate the global public interest in rheumatoid arthritis by evaluating search term popularity changes of the disease over a decade. Google Trends was applied to retrieve search popularity scores for the term ‘rheumatoid arthritis’ between January 2004 and December 2017, utilizing the category of “health”. Overall, relative searches volume for rheumatoid arthritis steadily decreased from January 2004 to December 2010, and then slowly rose from January 2011 to December 2017. There were significant seasonal variations in relative searches volume for the term ‘rheumatoid arthritis’ (Amplitude = 3.11; Phase: Month = 4.3; Low point: Month = 10.3; p

Objective To evaluate the impact of systemic lupus erythematosus (SLE) on health-related quality of life (HRQoL) assessed with SF-36 and explore factors associated with HRQoL in SLE patients. Methods A random-effect meta-analysis was performed to calculate extracted data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity. Results A total of 36 articles were finally included in this meta-analysis, including 6510 patients. The pooled mean scores of SF-36 physical component summary and mental component summary were 46.10 (95% confidence interval (CI): 43.09–49.10) and 50.37 (95% CI: 47.78–52.87), respectively. Spearman's correlation analysis found that mean age, proportion of female participants, and publication decades were negatively associated with some of the SF-36 domains. Sample size and SLEDAI were positively associated with some of the SF-36 domains. Patients with SLE have lower HRQoL in comparison to the general population. Conclusions SLE has a significant impact on HRQoL, which proves that the necessity of improving HRQoL in SLE patients cannot be ignored. Measuring HRQoL should be considered as an indispensable part of the overall evaluation of health conditions of SLE patients.

OBJECTIVES The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

BACKGROUND Prolactin (PRL), an inflammatory hormone with cytokine properties, has long been proposed to play a crucial role in the pathogenesis of autoimmune disorders, including rheumatoid arthritis (RA). However, the circulating levels of PRL in RA were discordant among published studies. METHODS PubMed, Embase, and The Cochrane Library database were systematically searched from inception up to 30 June 2018. The available studies were obtained from the initial search in accordance with the rigorous inclusion and exclusion criteria. Relevant data from the included literatures were extracted. Methodological quality was evaluated in order to refine the final search results. All statistical analyses were conducted using software STATA version 12.0. RESULTS Of 698 articles were yielded for eligibility, a finally analysis involving 628 RA cases and 430 controls from 14 published studies were included. When compared to healthy controls, there was a significantly higher level of circulating PRL in patients with RA with a pooled SMD of 1.08 (95% CI = 0.41 to 1.74, P

Aim: We performed this meta-analysis in order to evaluate circulating interleukin-8 (IL-8) levels in systemic lupus erythematosus (SLE) patients more accurately and explore its related influencing factors. Methods: The related literature was systematically searched in PubMed, Embase and The Cochrane Library database (up to 28 March 2018). All data analysis was performed by Stata 12.0 software. Results: The results showed SLE patients had a higher circulating IL-8 levels than normal controls (pooled standardized mean difference = 0.963; 95% CI: 0.416–1.511). Subgroup analyses indicated SLE patients with age

Currently published data regarding the potential role of osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the discrimination between rheumatoid arthritis (RA) and osteoarthritis (OA) are contradictory. To derive a more precise evaluation, a meta-analysis was performed.Published literatures comparing plasma/serum OPG, OCN and OPN levels between RA group and OA controls were searched in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using INine studies including 438 RA patients and 255 OA patients were finally incorporated in the meta-analysis after examining title, type, abstracts and full text. The results showed that RA patients had higher plasma/serum OPN (pooled SMD = -2.57, 95% CI = -4.72 to -0.41) levels when compared to OA patients. No significant difference in plasma/serum OPG (pooled SMD = -0.29, 95% CI = -1.07‒0.49) and OCN (pooled SMD = -0.09, 95% CI = -0.48‒0.31) levels were found between RA patients and OA patients. Subgroup analysis indicated that plasma/serum OPG levels had no significant differences between RA patients and OA patients in Europe and Asian.Overall, there is no significant difference in circulating OPG and OCN levels between RA patients and OA patients. However, plasma/serum OPN level is significantly higher in RA patients compared with OA patients.

Background and Aims: Matrix metalloproteinase-9 (MMP-9) is closely related to the pathogenesis of autoimmune diseases, especially Systemic Lupus Erythematosus (SLE). However, published works about the circulating MMP-9 levels in SLE are contradictory. A meta-analysis was performed to estimate circulating MMP- 9 levels in SLE patients more accurately and explore its related influencing factors. Methods: The related literatures were systematically searched in PubMed, Embase, and The Cochrane Library database (up to 31 January 2018). Pooled Standardized Mean Difference (SMD) and 95% Confidence Interval (CI) of circulating MMP-9 levels were calculated by Stata12.0 software according to fixed-effect or randomeffect model analysis. Results: A total of 638 articles were retrieved, and 12 studies including 730 SLE cases and 759 controls were finally included in the meta-analysis. No significant differences in circulating MMP-9 levels were observed between SLE patients and healthy controls (pooled SMD = -0.209, 95% CI = -0.812 to 0.394). However, subgroup analyses indicated that age Conclusion: The meta-analysis of current evidence suggests that circulating MMP-9 levels do not differ between SLE patients and healthy controls, however, the results may be affected by age and sample size. Further studies are needed to clarify the relationship between SLE and circulating MMP-9 levels.

Currently, many studies have focused on the possibility of using mean platelet volume (MPV) as a biomarker for disease activity in patients with systemic lupus erythematosus (SLE). To derive a more accurate estimation, a meta-analysis was conducted. Embase, PubMed, The Cochrane Library database and several Chinese databases (up to Nov 1 2017) were used to acquire published literatures on association of MPV levels with disease activity in SLE patients. Fixed-effects or random-effect model analysis was performed to calculate pooled standard mean difference (SMD) with 95% confidence interval (CI). Heterogeneity test was tested by the Q statistic and quantified using I2. A funnel plot and Egger’s linear regression test were used to evaluate the potential publication bias. A total of 618 articles were identified, nine studies with 376 active SLE patients and 270 inactive SLE patients were finally included. No significant difference in MPV level was found between active SLE patients and inactive SLE patients (SMD = − 0.05, 95% CI: − 0.83, 0.73). Subgroup analyses stratified by age or region also demonstrated consistent results. No significant publication bias was observed (P > 0.05). The sensitivity analysis showed no significant change when any one study was excluded. In summary, our meta-analysis does not support the use of MPV as an indicator for monitoring disease activity in SLE patients. Further longitudinal studies with larger sample size are warranted to unveil the possibility of using MPV as a biomarker of disease activity.

Background Systemic lupus erythematous (SLE) is a complex autoimmune disease with female predominance, particularly affecting those of childbearing age. We performed analysis of three genome-wide genotyping datasets of populations of both Chinese and European origin. Methods This study involved 5695 cases and 10,357 controls in the discovery stage. The lead signal on chromosome X was followed by replication in three additional Asian cohorts, with 2300 cases and 4244 controls in total. Conditional analysis of the known associated loci on chromosome X was also performed to further explore independent signals. Results Single-nucleotide polymorphism rs13440883 in GPR173 was found to be significantly associated with SLE (Pmeta = 7.53 × 10− 9, ORmeta= 1.16), whereas conditional analysis provided evidence of a potential independent signal in the L1CAM-IRAK1-MECP2 region in Asian populations (rs5987175 [LCA10]). Conclusions We identified a novel SLE susceptibility locus on the X chromosome. This finding emphasizes the importance of the X chromosome in disease pathogenesis and highlights the role of sex chromosomes in the female bias of SLE. Electronic supplementary material The online version of this article (10.1186/s13075-018-1590-3) contains supplementary material, which is available to authorized users.

Clinical toxoplasmosis in AIDS/HIV patients is a great public health concern around the world. Untreated Toxoplasma gondii (T. gondii)-infections are often fatal in AIDS/HIV patients. This study aims to assess the seroprevalence and odds ratio (OR) of T. gondii in AIDS/HIV patients, as well as the potential influential factors. Studies published from December 1, 1983 to December 1, 2016 in English, which comparing the seroprevalence of T. gondii between AIDS/HIV patients and control group were searched in PubMed, EMBASE and The Cochrane Library databases. The non-weighted prevalence, pooled fixed-effect or random-effect model estimates of OR and its 95% confidence intervals (CI) were all calculated. Heterogeneity test was performed by the Q statistic and quantified using I2, publication bias was evaluated using a funnel plot and Egger's linear regression test. A total of 4220 articles were obtained after searching databases, and 12 studies with 2101 AIDS/HIV patients and 5851 controls were incorporated in the meta-analysis. Meta-analysis revealed that, compared with the control group, the AIDS/HIV group had a higher seroprevalence of T. gondii (46.12% vs 36.56%) (OR=1.55, 95%CI: 1.19-2.04). Subgroup analyses showed that publication year, race, geographic locations and diagnostic methods are positive associated with the seroprevalence of T. gondii. Overall, our study suggests that AIDS/HIV patients have higher seroprevalence of T. gondii than those without.

This study aimed to systemically review the evidence regarding the relationship between the circulating blood osteoprotegerin (OPG) level and rheumatoid arthritis (RA), as well as the potential influential factors. Research related to plasma/serum OPG levels in RA patients and healthy controls were gathered using PubMed, EMBASE, and The Cochrane Library database (up to Jan. 1, 2017). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2, and publication bias was evaluated using a funnel plot and Egger's linear regression test. After searching databases, 443 articles were obtained, and 11 studies with 710 RA patients and 561 controls were finally included. Meta-analysis revealed that, compared with the control group, the OPG level was significantly higher in the RA group (P

Systemic lupus erythematosus (SLE) is associated with increased cardiovascular risk. This study aims to derive a more precise estimation on pulse wave velocity (PWV) level in patients with SLE and related factors. A literature search was performed using PubMed, EMBASE, and The Cochrane Library databases, studies published up to February 28, 2017, in English. Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I2; publication bias was evaluated using a funnel plot and Egger’s linear regression test. Of 156 studies found, 27 met eligibility criteria, and 14 studies were finally included in the meta-analysis. Meta-analysis revealed that the SLE group had significantly higher PWV levels than the control group; SMD = 0.56 and 95% CI (0.30-0.82). Subgroup analyses showed that body mass index (BMI), sample size, and disease duration were associated with PWV in patients with SLE. Overall, our study suggests that patients with SLE have a higher PWV level, and it is associated with BMI, sample size, and disease duration.

BACKGROUND This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). MATERIAL AND METHODS Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). RESULTS The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. CONCLUSIONS The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients.

// Guo-Cui Wu 1, 2 , Hui Yuan 3 , Hai-Feng Pan 1, 2 and Dong-Qing Ye 1, 2 1 Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China 2 Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis, Hefei, Anhui, China 3 Department of Preventive Medicine, Wannan Medical College, Wuhu, Anhui, China Correspondence to: Hai-Feng Pan, email: panhaifeng@ahmu.edu.cn , panhaifeng1982@sina.com Dong-Qing Ye, email: ydq@ahmu.edu.cn , ydqahmu@gmail.com Keywords: midkine, pleiotrophin, systemic lupus erythematosus, IL-17 Received: October 04, 2016 Accepted: November 18, 2016 Published: November 26, 2016 ABSTRACT Emerging evidence suggests that two heparin-binding growth factor, midkine and pleiotrophin are implicated in the pathogenesis of autoimmune diseases including SLE. To investigate the plasma midkine and pleiotrophin levels in SLE patients, as well as their correlation with major clinical parameters and interleukin-17 (IL-17) level in SLE, 83 SLE patients and 123 controls including 20 rheumatoid arthritis (RA) patients, 21 Sjogren’s syndrome (SS) patients and 82 healthy controls (HCs) were recruited. Plasma midkine, pleiotrophin and IL-17 levels were detected by ELISA. Midkine and pleiotrophin levels were significantly higher in SLE, RA and SS patients compared with HCs (all P < 0.05). There were significantly lower midkine and pleiotrophin levels in SLE compared to SS ( P < 0.05 and P < 0.01, respectively). No significant differences in midkine and pleiotrophin levels were found between SLE and RA ( P = 0.240 and P = 0.074, respectively). Both plasma midkine and pleiotrophin levels were associated with rash and anti-SSA in SLE. In addition, both midkine and pleiotrophin levels were positively associated with IL-17 level in SLE (both P < 0.001). Area under curve (AUC) of the receiver operating characteristic (ROC) curve for midkine and pleiotrophin were 0.606 (0.527–0.681) and 0.605 (0.526–0.680) respectively. In conclusion, elevated plasma midkine and pleiotrophin levels and their associations with rash, anti-SSA and IL-17 in SLE patients suggest their involvement in this disease.

Aim: An existing meta-analysis have investigated the PTX3 levels in systemic lupus erythematosus (SLE) patients, but the number of studies has increased since 2015. We performed an updated meta-analysis to derive a more accurate estimation. Methods: The related literature was systematically searched in PubMed, Embase and The Cochrane Library database (up to 28 February, 2019). Results: SLE patients had significantly higher PTX3 levels than controls (pooled SMD = 0.48; 95% CI: 0.11–0.84). Subgroup analyses indicated SLE patients from non-Caucasian population, with age ≥45 years, SLE disease activity index (SLEDAI) ≥10 and plasma samples had higher PTX3 levels. Conclusion: Circulating PTX3 levels are increased in SLE patients, and affected by age, ethnicity, SLEDAI and sample type.

Aryl hydrocarbon receptor (AhR), a type of transcriptional factor, is widely expressed in immune cells. The activation of AhR signaling pathway depends on its ligands, which exist in environment and can also be produced by metabolism. Normal expressions of AhR and AhR-mediated signaling may be essential for immune responses, and effects of AhR signaling on the development and function of innate and adaptive immune cells have also been revealed in previous studies. Recent studies also indicate that aberrant AhR signaling may be related to autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune uveitis (AU), autoimmune diabetes, Behcet's disease (BD) and myasthenia gravis (MG). Moreover, administration of AhR ligands or drugs has been proven effective for improving pathological outcomes in some autoimmune diseases or models. In this review, we summarize the effects of AhR on several innate and adaptive immune cells associated with autoimmunity, and the mechanism on how AhR participates in autoimmune diseases. In addition, we also discuss therapeutic potential and application prospect of AhR in autoimmune diseases, so as to provide valuable information for exploring novel and effective approaches to autoimmune disease treatments.

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single‐nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health‐related quality of life (HRQoL) was also measured by SF‐36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (P BH = 0.039), and this association was more pronounced in the female subgroup (P BH = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role‐emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs.

Conclusion: Patients with RA have lower circulating IGF-1 level than healthy controls, particularly for patients from Asia and Europe. Further studies are necessary to elucidate the role of IGF-1 in the pathological process of RA. Results: A total of eleven articles with 334 cases and 261 controls were finally included. Compared with the healthy group, the RA group had lower circulating IGF-1 levels (pooled SMD= -0.936, 95% CI= -1.382 to -0.489, p Methods: PubMed, Embase and the Cochrane Library databases were searched up to December 2018 in English, and the studies comparing serum/plasma IGF-1 levels between RA group and healthy control group were what we are interested in. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of the included studies. The heterogeneity test was performed by the Cochrane Q statistic and I2 –statistic. The publication bias was evaluated by the funnel plot and Egger’s test. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the fixed-effects or random-effects model. Background and Objectives: Insulin-like growth factor-1 (IGF-1) levels have been investigated in rheumatoid arthritis (RA), however, produced inconsistent results. The purpose of this meta-analysis was to derive a more precise conclusion about serum/plasma IGF-1 levels in RA patients.

To investigate the plasma galectin-3 levels in systemic lupus erythematosus (SLE) patients and its relations with clinical and laboratory features.A total of 180 subjects with 90 patients with SLE (8 male, 82 female, mean age 37.86 ± 13.98 years) and 90 healthy controls (8 male, 82 female, mean age 36.54 ± 10.89 years) were included. Plasma galectin-3 levels were detected by enzyme-linked immunosorbent assay (ELISA).There was no significant difference in age and gender distribution between SLE patients and healthy controls (both P .05). Plasma galectin-3 level was not significantly different between SLE patients and controls (P = .982) (P .05). No significant difference was found regarding galectin-3 levels between SLE with nephritis and those without nephritis (P .05); no significant difference was found between less active SLE and more active SLE (P .05). Galectin-3 levels were inversely related to immune globulin M (r = -.303, P .05), while no significant correlation between galectin-3 levels and other quantitative laboratory parameters were observed (all P .05).In summary, plasma galectin-3 level was not significantly different between SLE patients and controls (P = .982). Further studies are needed to elucidate the role of galectin-3 in SLE.

Rheumatoid arthritis (RA) patients have increased risk of cardiovascular disease (CVD) death. Elevated asymmetric dimethylarginine (ADMA) levels have been reported to be an independent predictor of CVD morbidity and mortality, however, the role of ADMA in RA remains undetermined. To derive a more accurate estimation on circulating ADMA levels in RA patients, a meta-analysis was performed. Embase, PubMed, and The Cochrane Library database (up to October 7 2018) were used to acquire published literatures. Heterogeneity test was performed by the Q statistic and quantified using I2. Publication bias was evaluated using a funnel plot and Egger’s linear regression test. A total of 174 articles were identified, 16 studies with 1365 subjects (666 RA patients and 699 healthy individuals) were ultimately included. Plasma/serum ADMA levels appeared to be higher in RA patients than healthy controls (SMD = 0.84, 95% CI 0.32, 1.35). By assessing the BMI, age, disease duration and disease activity as subgroups, BMI ≥ 24 and BMI

Air pollution is an important risk factor for autoimmune diseases, but its association with the recurrence of rheumatoid arthritis (RA) remains unclear so far. This study aimed to investigate the short-term association between traffic-related air pollutants and hospital readmissions for RA in Hefei, China. Data on daily hospital readmissions for RA and traffic-related air pollutants, including particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and carbon monoxide (CO), from 2014 to 2018 were retrieved. A time-series approach using generalized linear regression model was employed. The analysis was further stratified by sex, age and season. A total of 1153 readmissions for RA were reported during the study period. A significant association between high-concentration PM2.5 (90th percentile) and RA readmissions was observed on lag1 (relative risk (RR) = 1.09, 95% confidence interval (CI): 1.01–1.19) and lasted until lag3 (RR = 1.06, 95%CI: 1.01–1.12). From lag2 to lag5, high-concentration NO2 (90th percentile) was associated with increased risk of RA readmissions, with the highest RR observed at lag 4 (1.11, 95%CI: 1.05–1.17). Stratified analyses indicated that females and the elderly appeared to be more vulnerable to high-concentration PM2.5 and NO2 exposure. High-concentration PM2.5 and NO2 in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM2.5 and NO2 was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM2.5 and NO2 should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons.

In order to determine whether tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene polymorphisms confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted to examine the association between TNFAIP3 polymorphisms and susceptibility to SLE. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. A total of 23 studies from 20 articles, involving 18,501 patients with SLE and 30,435 healthy controls were included in this meta-analysis. Overall, we found significant association between SLE and the TNFAIP3 rs2230926, rs5029937, rs5029939, and rs3757173 polymorphisms (all P < 0.001). Stratification by ethnicity indicated that rs5029939 polymorphism was associated with SLE in Europeans, while rs2230926, rs5029937, and rs3757173 polymorphisms were associated with SLE both in Europeans and Asians (all P < 0.001). The results of our meta-analysis suggest that TNFAIP3 (rs2230926, rs5029937, rs5029939, and rs3757173) polymorphisms are associated with susceptibility to SLE.

Autoimmune diseases contain a large number of pathologies characterized by various factors that contribute to a breakdown in self-tolerance. Cytokine-mediated immunity plays an essential role in the pathogenesis of varieties of autoimmune diseases. Recent studies reveal that interleukin-35 (IL-35), a newly identified cytokine of IL-12 family, is implicated in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), etc. In this review, we will discuss the biological features of IL-35 and summarize recent advances in the role of IL-35 in the development and pathogenesis of autoimmune diseases; the discoveries gained from these findings might translate into future therapies for these diseases.

OBJECTIVE A recent genome-wide association study identified that genetic variants in DPP4 and CCR6 are connected with a risk of RA in the Han Chinese population. The aim of this study was to estimate the epistatic interaction between DPP4 and CCR6 in RA. METHODS Two single-nucleotide polymorphisms identified in a Han Chinese genome-wide association study (rs12617656 in DPP4, rs1854853 in CCR6) were genotyped. Logistic regression was used to estimate the multiplicative interaction and the additive interaction was analysed by 2 × 2 factorial design. RESULTS A total of 1224 subjects (377 RA patients, 847 healthy controls) were included in the initial analysis. Additionally, 600 patients with lupus arthritis were included for comparison. Significant multiplicative interaction between DPP4 and CCR6 was observed in RA [codominant model: odds ratio (OR) = 1.49, P = 0.003]. The epistatic effect seems to be stronger in ACPA-positive RA (codominant model: OR = 1.66, P = 0.001). However, no significant multiplicative interactions were observed in ACPA-negative RA or lupus arthritis. Additive interaction analysis showed a significant epistatic effect, but only in ACPA-positive RA [attributable proportion due to interaction = 0.48 (95% CI 0.10, 0.85)]. A further replication study of an independent cohort (476 subjects) found similar results. Pooled results confirmed that there was significant interaction between DPP4 and CCR6 on both the multiplicative and additive scales. CONCLUSION The study suggests that a genetic interaction between DPP4 and CCR6 is involved in RA susceptibility. Furthermore, these findings highlight Th17 cell response as an important contributor in the pathogenesis of RA.

The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. A total of 386 RA patients were enrolled along with 576 matched healthy controls. Genotyping was performed by using TaqMan genotyping assays on Fluidigm 192.24 system. For the meta-analysis, a systematic literature search was conducted to identify all relevant studies. This case control study showed that the IRAK1 rs3027898 C allele was associated with increased risk of RA with an odds ratio (OR) = 1.4 and 95 % confidence intervals (CI) = 1.093–1.793, P = 0.008 but miR-499 rs3746444 polymorphisms were not significantly associated with the risk for RA. The meta-analyses included a total of 4 case control studies on IRAK1 rs3027898 and 4 studies on miR-499 rs3746444. The IRAK1 rs3027898 C allele had an overall OR of 1.268 (95 % CI = 1.130–1.424, P < 0.001). After stratification by ethnicity the C allele had an OR of 1.238 (95 % CI = 1.096–1.398, P = 0.001) in Asians. No association between miR-499 rs3746444 polymorphism and RA was found in the overall and Asian populations. The results from our case control study and the meta-analyses indicate that the IRAK1 rs3027898 C allele is significantly associated with an increased risk of RA, especially in Asians.

Systemic lupus erythematosus (SLE) is associated with increased risk of cardiovascular disease. Carotid intima media thickness (CIMT) and carotid plaques are both frequently used to identify populations at higher cardiovascular risk. A systematic literature search and meta-analysis were performed to evaluate CIMT and carotid plaques difference between SLE patients and normal controls.The literatures comparing markers of cardiovascular risk (CIMT and prevalence of carotid plaques) in SLE and controls were systematically searched in PubMed, EMBASE and Cochrane databases. The overall mean CIMT difference and pooled odds ratio (OR) for the prevalence of carotid plaques between SLE patients and control groups were calculated by fixed-effects or random-effect model analysis. Meta-regression was performed to explore the potential influencing factors. Publication bias was examined by a funnel plot and Egger's test.A total of 80 studies (6085 SLE patients and 4794 controls) were included in the final analysis, 71 studies with data on CIMT (4814 cases and 3773 controls) and 44 studies reporting on the prevalence of carotid plaques (4417 cases and 3528 controls). As compared to controls, SLE patients showed a higher CIMT (WMD: 0.07 mm; 95%CI: 0.06, 0.09; P0.001), and an increased prevalence of carotid plaques (OR: 2.45; 95%CI: 2.02, 2.97; P0.001). Meta-regression models showed that traditional cardiovascular risk factors (age, HDL and triglyceride of SLE patients) and lupus related risk factors (as expressed by duration, ESR, SLEDAI and steroids) had a significant influence on CIMT, steroids and triglyceride had significant influence on the prevalence of carotid plaques.Our findings support the current evidence base for an increased cardiovascular burden in SLE patients and support the use of CIMT and carotid plaques in observational studies in SLE patients. The findings are of importance to design more specific prevention and treatment strategies.

This study aims to derive a more precise estimation on carotid intima-media thickness (CIMT) level in patients with rheumatoid arthritis (RA) and related factors. Studies published from January 1, 1982 to December 31, 2014 in English, which comparing CIMT between RA group and control group were searched in PubMed, Embase, and Cochrane Library databases. Heterogeneity test was performed, and publication bias was evaluated. Stata software 12.0 was used to perform the meta-analysis. Two-thousand one hundred sixty-three articles were obtained after searching databases, and 47 studies were finally included in the meta-analysis. The result of the analysis in random effect model showed that RA group had significantly higher CIMT than control group, with the standardized mean difference (SMD) of 1.04 and 95% CI (0.81,1.27). To evaluate the stability of our results, sensitivity analyses were performed, and the results showed no significant change when any one study was excluded. Subgroup analyses showed that region, race, age, BMI, and disease duration were associated with CIMT in RA patients. In summary, CIMT in RA patients is thicker than healthy controls, and it is influenced by region, race, age, BMI, and disease duration.

Background:Recent studies have focused on the special roles of NADPH-oxidase, which is composed of gp91phox, p22phox, p47phox, p67phox, p40phox encoded byCYBB,CYBA,NCF1,NCF2,NCF4genes, in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in Chinese population.Objectives:We performed this study to examine the association ofNCF2,NCF4,CYBAgenes polymorphisms with RA susceptibility in a Chinese population.Methods:Six single nucleotide polymorphisms (SNPs) (NCF2rs10911363,NCF4rs1883112, rs4821544, rs729749,CYBArs3794624, rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. All patients were consecutively enrolled from the Department of Rheumatology at the First Affiliated Hospital of University of Science and Technology of China and the First Affiliated Hospital of Anhui Medical University, and the normal controls was enrolled from the same region. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. Chi-square (χ2) test was used to analyze the association of the genotype and allele frequencies of above SNPs and RA. Odds ratios (OR) and 95% confidence interval (CI) were also evaluated using Logistic regression analyses, and haplotype analysis was assessed using SHEsis software.Results:There were 101 males and 492 females in RA group with a mean age of 51.59±6.68 years, and the normal control group included 97 males and 499 females with an average age of 52.32±12.63 years. We observed thatNCF4rs4821544 CT genotype, C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT:P= 0.043; C vs. T:P= 0.031), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC:P= 0.031). Moreover, our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC:P= 0.033). No significant association betweenNCF2,CYBAgenes polymorphisms and RA susceptibility was observed. There were no significant differences in allele, genotype frequencies of above SNPs between RA patients with RF-positive and with RF-negative, as well as anti-CCP-positive RA patients and anti-CCP-negative RA patients.Conclusion:In summary,NCF4rs4821544, rs729749 polymorphisms might contribute to RA susceptibility, whileNCF2,CYBAgenes polymorphisms were not associated with RA susceptibility.References:[1]Nauseef WM. Assembly of the phagocyte NADPH oxidase, Histochem Cell Biol, 2004;122:277-291.[2]Groemping Y, Rittinger K. Activation and assembly of the NADPH oxidase: a structural perspective, Biochem J (2005) 386:401-416.[3]Olsson LM, Nerstedt A, Lindqvist AK, Johansson SC, Medstrand P, Olofsson P, et al. Copy Number Variation of the Gene NCF1 Is Associated with Rheumatoid Arthritis, Antioxid Redox Signal(2012)16:71-78.DOI:10.1089/ars.2011.4013Table 1.Genotype and allele frequencies ofNCF2, NCF4, CYBAgenes polymorphisms in RA patients and controls [n(%)]SNPAnalyze modelRA (N = 593)Control (N = 596)P valueNCF2rs10911363GenetypesGG1251440.371GT3042890.747TT164163AllelesG5545770.408T632615NCF4rs1883112GenetypesGG57560.972GA2482550.754AA288285AllelesG3623670.888A824825rs4821544GenetypesCC470.323CT1171460.043TT472443AllelesC1251600.031T10611032Dominant modelTT4724430.031CT+CC121153rs729749GenetypesTT1041020.445CT2663020.033CC223192AllelesT4745060.219C712686CYBArs3794624GenetypesAA14150.929GA1601470.368GG41943AllelesA1881770.498G9981015rs4673GenetypesAA150.140GA85900.673GG507501AllelesA871000.34G10991092Acknowledgments:noDisclosure of Interests:None declared

Cardiovascular (CV) risk in type 1 diabetes mellitus (T1DM) is increased. In this study, we evaluated the differences in major markers of CV risk between patients with T1DM and healthy controls by a systematic review and meta-analysis. Literature from PubMed, EMBASE, and The Cochrane Library comparing CV risk markers between patients with T1DM and controls was obtained. The overall standard mean differences (SMDs) of carotid intima–media thickness (cIMT), endothelium-dependent flow-mediated dilation (FMD%), carotid-femoral pulse wave velocity (cf-PWV), and glyceryl trinitrate-mediated dilatation (GTN%) with its 95% confidence interval (CI) between patients with T1DM and control groups were calculated using fixed-effect or random-effect model. Heterogeneity was evaluated using the Cochran Q and I2 statistics. The results showed that patients with T1DM had a significantly greater cIMT (SMD: 0.89; 95% CI, 0.69-1.09; P < .001), significantly lower FMD% (SMD: −1.45%; 95% CI, −1.74 to −1.17; P < .001), significantly increased cf-PWV (SMD: 0.57; 95% CI, 0.03-1.11; P < .001), and significantly decreased GTN% (SMD: −1.11; 95% CI, −1.55 to −0.66; P < .001) than controls. Our results support the current evidence for an elevated CV burden in patients with T1DM and affirm the clinical utility of markers of subclinical atherosclerosis in the management of these patients.

OBJECTIVES The aim of our study was to evaluate two lncRNAs (lnc0640 and lnc5150) expressions and gene single-nucleotide polymorphisms (SNPs) in rheumatoid arthritis (RA) patients. METHODS The expressions of lncRNAs in peripheral blood mononuclear cells (PBMCs) were examined by quantitative real-time reverse transcription polymerase chain reaction from 65 RA patients and 54 controls. Simultaneously, three SNPs (rs13039216, rs6085189, and rs6085190) of lnc0640, three SNPs (rs1590666, rs141561256, and rs144047453) of lnc5150 were genotyped using TaqMan SNP-genotyping assays in 627 RA patients and 590 controls. RESULTS The lnc0640 level in PBMCs from RA patients was significantly increased (P = 0.001), whereas the lnc5150 level was significantly reduced (P

Although the current glucocorticoids (GCs) treatment for systemic lupus erythematosus (SLE) is effective to a certain extent, the difference in therapeutic effect between patients is still a widespread problem. Some patients can have repeated attacks that greatly diminish their quality of life. This study was conducted to investigate the relationship between HSP90AA2 polymorphisms and disease susceptibility, GCs efficacy and health-related quality of life (HRQoL) in Chinese SLE patients. A case-control study was performed in 470 SLE patients and 470 normal controls. Then, 444 patients in the case group were followed up for 12 weeks to observe efficacy of GCs and improvement of HRQoL. Two single nucleotide polymorphisms (SNPs) of HSP90AA2 were selected for genotyping: rs1826330 and rs6484340. HRQoL was assessed using the SF-36 questionnaire. The minor T allele of rs1826330 and the TT haplotype formed by rs1826330 and rs6484340 showed associations with decreased SLE risk (T allele: PBH = 0.022; TT haplotype: PBH = 0.033). A significant association between rs6484340 and improvement of HRQoL was revealed in the follow-up study. Five subscales of SF-36 were appeared to be influenced by rs6484340: total score of SF-36 (additive model: PBH = 0.026), physical function (additive model: PBH = 0.026), role-physical (recessive model: PBH = 0.041), mental health (dominant model: PBH = 0.047), and physical component summary (additive model: PBH = 0.026). No statistical significance was found between HSP90AA2 gene polymorphisms and GCs efficacy. These results revealed a genetic association between HSP90AA2 and SLE. Remarkably, HSP90AA2 has an impact on the improvement of HRQoL in Chinese population with SLE.

Currently published data regarding the relationship between plasma/serum leptin levels and systemic lupus erythematosus (SLE) are contradictory. To derive a more precise evaluation of this relationship, a meta-analysis was performed.Published literature from PubMed, Embase and Cochrane Library were obtained. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity among studies was estimated using the Cochran Q and I(2) statistics.A total of 11 studies including 868 SLE patients and 591 controls were finally included in the meta-analysis. No significant differences in plasma/serum leptin levels was found between SLE patients and healthy controls when all studies were pooled into the meta-analysis (pooled SMD = 0.269, 95% CI = -0.188 to 0.726). However, subgroup analyses showed that SLE patients from an Asian population, age ≥40 years and BMI25 had higher plasma/serum leptin levels when compared with controls.There is no significant difference in plasma/serum leptin levels between the entire group of SLE patients and controls. However, plasma/serum leptin levels are significantly higher in the subgroup of SLE patients from an Asian population ≥40 years of age and with a BMI25.

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.

The aim of this study was to investigate the association of interleukin (IL)-10 gene single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. 848 SLE patients and 461 normal controls were recruited in this study. Nine SNPs in IL-10 gene (rs1518110, rs1518111, rs1554286, rs1800890, rs1800893, rs3024493, rs3024495, rs3024498 and rs6667202) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The frequency of IL-10 rs3024498-C allele was significantly higher in patient group compared with control subjects (OR=5.118, 95% CI=1.819-14.405, P=0.002). No significant differences were detected for the distribution of allele and genotype frequencies of other eight SNPs between patients with SLE and controls after Bonferroni correction (all P>0.0056). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs3024498 between SLE patients with and without arthritis (P=0.002, P=0.022, respectively).There was significant difference in genotype frequency at rs3024498 between SLE patients with and without malar rash (P=0.040). And, there was significant difference in allele frequency at rs3024498 between SLE patients with and without anti-double-stranded DNA (P=0.032). Meanwhile, significant difference in genotype frequency at rs1518110 and rs1518111 were found in patients with and without lupus headache (P=0.025, P=0.038, respectively). There were significant difference in allele and genotype frequency at rs1800890 and rs6667202 between SLE patients with and without thrombocytopenia (rs1800890: P=0.016, P=0.026, respectively; rs6667202: P=0.007, P=0.007, respectively). Further, significant difference were observed both in allele frequency and in genotype distribution of rs1800893 between patients with and without tubular urine and proteinuria (tubular urine: P