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Xue-Hui Fang,1,* Yi-Lin Dan,2,* Jie Liu,1 Lei Jun,1 Zhi-Ping Zhang,3 Xiao-Hong Kan,1 Dong-Chun Ma,1 Guo-Cui Wu41Department of Science and Education, Anhui Provincial TB Institute, Hefei, Anhui, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Tuberculosis Prevention, Anqing Center for Disease Control and Prevention, Anqing, Anhui, People’s Republic of China; 4School of Nursing, Anhui Medical University, Hefei, Anhui, People’s Republic of China *These authors contributed equally to this work Objective: This study aimed to understand the influencing factors of treatment completion among pulmonary tuberculosis (PTB) patients in Anhui province, eastern People’s Republic of China, in order to provide scientific evidence for improving the follow-up rate and treatment completion rate.Methods: A total of 262 PTB patients in six counties (districts) of Anhui province were investigated by questionnaire, and data about treatment interruption were collected.Results: The main causes of treatment interruption were forgetting to take medicine (24.5%), drug side effects (23.3%), and symptomatic improvement (19.5%). The education background, patient type, cause of interruption, and tracking method were factors influencing completion of treatment (all P

Background: Antisocial behavior (ASB) infringes on the rights of others and significantly disrupts social order. Studies have shown that ASB is phenotypically associated with various psychiatric disorders. However, these studies often neglected the importance of genetic foundations., Methods: This study utilized genome-wide association studies and pleiotropy analysis to explore the genetic correlation between ASB and psychiatric disorders. Linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods were employed to assess genetic correlations, and the PLACO method was used for pleiotropy analysis. Functional annotation and biological pathway analysis of identified pleiotropic genes were performed using enrichment analysis. Furthermore, Mendelian randomization (MR) analysis was conducted to validate these causal relationships., Results: LDSC and HDL analysis showed that significant positive genetic correlations were between ASB and attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Multiple potential pleiotropic genetic loci were identified, particularly the FOXP2 and MDFIC genes located at the 7q31.1 locus. Enrichment analysis showed that these pleiotropic genes are highly expressed in several brain regions (such as the hypothalamus, cerebellar hemisphere, cortex, and amygdala) and immune-related cells. MR analysis further confirmed the causal effects ADHD, SCZ, and MDD on ASB risk., Conclusion: This study reveals significant genetic correlations and potential causal mechanisms between ASB and various psychiatric disorders. The MR analysis confirmed the causal effects of psychiatric disorders on ASB. These findings deepen our understanding of the genetic architecture of psychiatric disorders and ASB., Competing Interests: Declaration of competing interest All authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objects: Previous studies have suggested a potential correlation between rheumatoid arthritis (RA) and biological aging, but the intricate connections and mechanisms remain elusive., Methods: In our study, we focused on two specific measures of biological age (PhenoAge and BioAge), which are derived from clinical biomarkers. The residuals of these measures, when compared to chronological age, are defined as biological age accelerations (BAAs). Utilizing the extensive UK Biobank dataset along with various genetic datasets, we conducted a thorough assessment of the relationship between BAAs and RA at both the individual and aggregate levels., Results: Our observational studies revealed positive correlations between the two BAAs and the risk of developing both RA and seropositive RA. Furthermore, the genetic risk score (GRS) for PhenoAgeAccel was associated with an increased risk of RA and seropositive RA. Linkage disequilibrium score regression (LDSC) analysis further supported these findings, revealing a positive genetic correlation between PhenoAgeAccel and RA. PLACO analysis identified 38 lead pleiotropic single nucleotide polymorphisms linked to 301 genes, providing valuable insights into the potential mechanisms connecting PhenoAgeAccel and RA., Conclusion: In summary, our study has successfully revealed a positive correlation between accelerated biological aging, as measured by BAAs, and the susceptibility to RA., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: 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., Method: 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)., Results: 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., Conclusion: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

There is a growing body of evidence suggesting an association between air pollution exposure and tuberculosis (TB) incidence, but no meta-analysis has assembled all evidence so far. This review and meta-analysis aimed to derive a more reliable estimation on the association between air pollution and TB incidence. PubMed, Embase and Web of Science electronic databases were systemically searched for eligible literature. The PECO framework was used to form the eligibility criteria. Effect estimates and 95% confidence intervals (CIs) published in the included studies were pooled quantitatively. Seventeen articles met the inclusion criteria. The pooled estimates showed that long-term exposure to particulate matter with an aerodynamic diameter ≤10 μm (PM 10 ) was associated with increased incidence of TB (per 10 μg/m 3 increase in concentrations of PM 10 : risk ratios (RR) = 1.058, 95% CI: 1.021-1.095). Besides, long-term exposure to sulfur dioxide (SO 2 ) and nitrogen dioxide (NO 2 ) were significantly associated with TB incidence (per 1 ppb increase, SO 2 : RR = 1.016, 95% CI: 1.001-1.031; NO 2 : 1.010, 95% CI: 1.002-1.017). We did not find a significant association of PM 2.5 , ozone (O 3 ) or carbon monoxide (CO) with TB risk, regardless of long-term or short-term exposure. However, in view of the 2016 ASA Statement and the biological plausibility of PM 2.5 damaging host immunity, the association between PM 2.5 and TB risk remains to be further established. This meta-analysis shows that long-term exposure to PM 10 , SO 2 or NO 2 is associated with increased odds of TB, and the specific biological mechanisms warrant further research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The circadian clock plays a crucial role in the progress of systemic lupus erythematosus (SLE). In this study, we performed a case-control study to explore the association between Period 2 (PER2) gene single nucleotide polymorphisms (SNPs) and the susceptibility of systemic lupus erythematosus (SLE). A total of 492 SLE patients and 493 healthy controls were included. The improved multiple ligase detection reaction (iMLDR) was used for genotyping. The correlations between four SNPs of PER2 (rs10929273, rs11894491, rs36124720, rs934945) and the genetic susceptibility and clinical manifestations of SLE were analyzed. Significant differences were observed in the distributions of allele frequencies and genotype under dominant model in rs11894491 between SLE patients and controls ( p  = 0.030, p  = 022, respectively). We hypothesized that PER2 gene SNPs was related to the genetic susceptibility and clinical manifestations, implying the potential role of PER2 in the pathogenesis of SLE.

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 < 5 × 10-8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects., 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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Currently, the correlation between ambient temperature and systemic lupus erythematosus (SLE) hospital admissions remains not determined. The aim of this study was to explore the correlation between ambient temperature and SLE hospital admissions in Hefei City, China. An ecological study design was adopted. Daily data on SLE hospital admissions in Hefei City, from January 1, 2007, to December 31, 2017, were obtained from the two largest tertiary hospitals in Hefei, and the daily meteorological data at the same period were retrieved from China Meteorological Data Network. The generalized additive model (GAM) combined with distributed lag nonlinear model (DLNM) with Poisson link was applied to evaluate the influence of ambient temperature on SLE hospital admissions after controlling for potential confounding factors, including seasonality, relative humidity, day of week, and long-term trend. There were 1658 SLE hospital admissions from 2007 to 2017, including 370 first admissions and 1192 re-admissions (there were 96 admissions with admission status not stated). No correlation was observed between ambient temperature and SLE first admissions, but a correlation was found between low ambient temperature and SLE re-admissions (RR: 2.53, 95% CI: 1.11, 5.77) (3.5 °C vs 21 °C). The effect of ambient temperature on SLE re-admissions remained for 2 weeks but disappeared in 3 weeks. Exposure to low ambient temperature may increase hospital re-admissions for SLE, and thus it is important for SLE patients to maintain a warm living environment and avoid exposure to lower ambient temperature.

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 (PM 2.5 and PM 10 ), nitrogen dioxide (NO 2 ), 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 PM 2.5 (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 NO 2 (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 PM 2.5 and NO 2 exposure. High-concentration PM 2.5 and NO 2 in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM 2.5 and NO 2 was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM 2.5 and NO 2 should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population., Methods: We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination., Results: No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05)., Conclusion: Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Sha-Sha Tao et al.)

Objective: To investigate the temporal trends in mortality and disease burden of injuries in Anhui province from 2008 to 2017, so as to provide reference for injury control and prevention., Methods: Data of mortality were collected from 9 national surveillance points in Anhui province during 2008-2017 in the Information System for Death Cause Register and Management. The surveillance data were analyzed by using crude mortality, standardized mortality rate (SMR), potential year of life lost (PYLL), PYLL rate (PYLLR), and average of year life lost (AYLL)., Results: There were a total of 44855 people died from injury, accounted for 9.44% of the all-cause mortality, ranked as the fifth leading cause of deaths in the whole population, and denoted the first leading cause of deaths in the 0-44 year's group. The leading causes of injury deaths were road traffic accidents, suicide, accidental falls, drowning, and poisoning. Road traffic accidents was the primary cause of injury deaths among the male population, while suicide was the dominate cause of injury deaths among the female population. Drowning, traffic accidents, and suicide accounted for the most injury deaths among the population aged 0-14 years, 15-64 years, and above 60 years, respectively. The road traffic accidents accounted for the largest proportion of injury PYLL and PYLLR, and drowning caused the highest AYLL among injury deaths., Conclusion: In Anhui province, road traffic accidents, suicide, accidental falls, drowning, and poisoning were the top five causes of injury deaths that harm the health of local residents; corresponding injury prevention strategies should be formulated., Competing Interests: The authors declared that they have no conflicts of interests., (Copyright © 2020 Xiu-Ya Xing et al.)

Objective: Although patients with psoriasis frequently report seasonal changes in their symptoms, the seasonality of psoriasis has rarely been explored. This study aims to investigate the seasonal pattern of and global public interest in psoriasis using Google search data., Methods: Internet search data were collected from Google Trends. Data on the relative search volume (RSV) from January 2004 to December 2018 were retrieved using the term psoriasis. Cosinor analyses were conducted to examine the seasonality of psoriasis using data from two southern hemisphere countries (Australia and New Zealand) and four northern hemisphere countries (USA, Canada, UK and Ireland)., Results: Overall, searches for psoriasis steadily decreased between 2004 and 2010, and then rose from 2011 to 2018. On cosinor analyses, RSV of 'psoriasis' displayed a significant seasonal variation worldwide ( p <0.025). Further analyses confirmed the seasonality of psoriasis-related RSV in Australia, New Zealand, USA, Canada, UK and Ireland ( p <0.025 for all), with peaks in the late winter/early spring months and troughs in the late summer/early autumn months. The top 11 rising topics were calcipotriol/betamethasone dipropionate, ustekinumab, apremilast, shampoo, eczema, guttate psoriasis, seborrhoeic dermatitis, dermatitis, psoriatic arthritis, atopic dermatitis and arthritis., Conclusion: There was a significant seasonal pattern for psoriasis, with peaks in the late winter/early spring and troughs in the late summer/early autumn. Further studies are warranted to confirm the seasonal pattern of psoriasis using clinical data and to explore the underlying mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study was to investigate the association of melatonin (MTN) pathway gene's single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE)., Methods: We recruited 495 SLE patients and 493 healthy controls, 11 tag SNPs in MTN receptor 1a ( MTNR1a ), MTNR1b , and arylalkylamine N-acetyltransferase ( AANAT ) genes were genotyped and analyzed. Serum MTN concentration was determined by enzyme-linked immunosorbent assay (ELISA) kits., Results: Two SNPs of AANAT gene (rs8150 and rs3760138) associated with the risk of SLE; CC carriers of rs8150 had a lower risk as compared to GG (OR = 0.537, 95% CI: 0.361, 0.799), whereas GG carrier in rs3760138 had an increased risk (OR = 1.823, 95% CI: 1.154, 2.880) compared to TT. However, we did not find any genetic association between the other nine SNPs with SLE risk. Case-only analysis showed associations of rs2165667 and rs1562444 with arthritis, rs10830962 with malar rash, rs3760138 with immunological abnormality, and rs8150 with hematological abnormality. Furthermore, a significant difference between plasma MTN levels with different genotypes of rs1562444 was observed. Haplotype analyses revealed that haplotype of CCTAT, CTAGT, and GGG was significantly associated with the increased risk in SLE susceptibility, but TCTAT and CTG appeared to be a protective haplotype., Conclusions: The present study supported the genetic association of MTN pathway genes with SLE susceptibility and specific clinical manifestations, suggesting the potential role of MTN pathway genes in the pathogenesis and development of SLE., Competing Interests: The authors confirm that there are no conflicts of interest., (Copyright © 2019 Peng Wang et al.)

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.

Recently, exposure to air pollutants has been associated with the development and progression of systemic lupus erythematosus (SLE). The current study aims to evaluate the effects of air pollutants on SLE hospital admissions in Bengbu, China. We performed distributed lag non-linear model combined with quasi-Poisson generalized linear regression to assess the impacts of air pollutants on SLE admissions from 2015 to 2017. Subgroup analyses by admission status (first admission or readmission) were also evaluated. A total of 546 hospital admissions during 2015-2017 were included. For single-day lag structures, the risk effects occurred from lag 2 to lag 9 for the 75th percentile particulate matter (PM) 2.5 , lag 3 to lag 9 for the 80th percentile PM 2.5 . For cumulative lag structures, the risk effects occurred from lag 0-5 to lag 0-14 for both 75th PM 2.5 and 80th PM 2.5 , and no significant effect was observed for 90th PM 2.5 . In addition, the adverse effects on SLE first admissions occurred from lag 0 to lag 1 for NO 2 , lag 1 to lag 2 for SO 2 . The maximum effect of PM 2.5 on SLE was 4.27 (95% confidence interval: 1.34-13.59) at lag 0-13 day, the minimum effect value was 1.12 (95% confidence interval: 1.03-1.23) at lag 9 day. These findings demonstrate that high PM 2.5 , NO 2 and SO 2 are associated with SLE hospital admissions. In addition, this study further revealed that exposure to high concentration of PM 2.5 increased the risk of SLE relapse, while high levels of NO 2 and SO 2 increased the risk of SLE first admissions.

Aim: 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., Methods: 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 (I 2 ) test, funnel plot and Egger's test, respectively. Sensitivity analyses were further examined by leave-one-out method., Results: Nineteen 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)., Conclusions: 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., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the plasma galectin-3 levels in systemic lupus erythematosus (SLE) patients and its relations with clinical and laboratory features., Methods: 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)., Results: 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)., Conclusions: 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., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Autoimmune diseases are a broad spectrum of disorders involved in the imbalance of T-cell subsets, in which interplay or interaction of Th1, Th17 and Tregs are most important, resulting in prolonged inflammation and subsequent tissue damage. Pathogenic Th1 and Th17 cells can secrete signature proinflammatory cytokines, including interferon (IFN)-γ and IL-17, however Tregs can suppress effector cells and dampen a wide spectrum of immune responses. Melatonin (MLT) can regulate the humoral and cellular immune responses, as well as cell proliferation and immune mediators. Treatment with MLT directly interferes with T cell differentiation, controls the balance between pathogenic and regulatory T cells and regulates inflammatory cytokine release. MLT can promote the differentiation of type 1 regulatory T cells via extracellular signal regulated kinase 1/2 (Erk1/2) and retinoic acid-related orphan receptor-α (ROR-α) and suppress the differentiation of Th17 cells via the inhibition of ROR-γt and ROR-α expression through NFIL3. Moreover, MLT inhibits NF-κB signaling pathway to reduce TNF-α and IL-1β expression, promotes Nrf2 gene and protein expression to reduce oxidative and inflammatory states and regulates Bax and Bcl-2 to reduce apoptosis; all of which alleviate the development of autoimmune diseases. Thus, MLT can serve as a potential new therapeutic target, creating opportunities for the treatment of autoimmune diseases. This review aims to highlight recent advances in the role of MLT in several autoimmune diseases with particular focus given to novel signaling pathways involved in Th17 and Tregs as well as cell proliferation and apoptosis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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 < 0.025). Relative searches volume peaked in April and reached the lowest level in October. The top 11 rising topics were scleroderma, Anna Marchesini, C-reaction protein, osteoarthritis, arthritis, joint pain, autoimmune disease, rheumatoid factor, rheumatology, methotrexate, and systemic lupus erythematosus, ranking from high to low by relative growth of topic regarding rheumatoid arthritis. In conclusion, the evidence from Google Trends analysis demonstrates a significant seasonal variation in rheumatoid arthritis, with a peak in April. In addition, the top rising search queries are beneficial for physicians to search the Internet themselves for websites that provide high-quality information to recommend to their patients.

Autoimmune diseases (ADs) are a broad spectrum of disorders featured by the body's immune responses being directed against its own tissues, resulting in prolonged inflammation and subsequent tissue damage. Recently, the exposure to ambient air pollution has been implicated in the occurrence and development of ADs. Mechanisms linking air pollution exposures and ADs mainly include systemic inflammation, increased oxidative stress, epigenetic modifications induced by exposures and immune response caused by airway damage. The lung may be an autoimmunity initiation site in autoimmune diseases (ADs). Air pollutants can bind to the Aryl hydrocarbon receptor (AHR) to regulate Th17 and Treg cells. Oxidative stress and inducible bronchus associated lymphoid tissue caused by the pollutants can influence T, B cells, resulting in the production of proinflammatory cytokines. These cytokines stimulate B cell and dendritic cells, resulting in a lot of antibodies and self-reactive T lymphocytes. Moreover, air pollutants may induce epigenetic changes to contribute to ADs. In this review, we will concern the associations between air pollution and immune-inflammatory responses, as well as mechanisms linking air pollution exposure and autoimmunity. In addition, we focus on the potential roles of air pollution in major autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 I 2 . 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 < 24 groups both showed elevated ADMA levels than controls, disease duration ≥ 8, age < 50 and disease activity ≥ 3.2 and < 5.1 group had a higher ADMA level than control groups. However, disease duration < 8, disease activity ≥ 5.1 and age ≥ 50 groups showed no difference between two groups. Circulating ADMA levels are higher in RA patients compared with healthy controls. In addition, ADMA levels are influenced by age, disease duration and disease activity.

Interleukin-35 (IL-35) exerts crucial roles in the pathogenesis and development of systemic lupus erythematosus (SLE), in this study we aim to explore the associations between IL-35 gene polymorphisms and the susceptibility, clinical features and plasma IL-35 levels of SLE patients, respectively. 490 SLE patients and 489 healthy controls were recruited in our study. The correlations between the polymorphisms of seven SNPs of IL-35 encoding gene and the susceptibility, main clinical manifestations of SLE were evaluated, respectively. Plasma IL-35 levels were assessed in 76 SLE patients, and the associations between plasma IL-35 levels and the polymorphisms of genotyped SNPs were explored. There were significant associations between the polymorphisms of rs4740 and the occurrence of renal disorder, hematological disorder in SLE patients, respectively ( p = 0.001; p = 0.001). In addition, there were no significant associations observed between the genotype frequencies of genotyped SNPs and the risk of SLE, plasma IL-35 levels, respectively. The polymorphism of rs4740 of IL-35 encoding gene is associated with the occurrence of renal disorder and hematological disorder of SLE patients.

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< 0.001), particularly in Asians, age ≥50, enzyme-linked immunosorbent assay (ELISA) group and subjects with erythrocyte sedimentation rate (ESR) ≥25 mm/h., Conclusions: Our meta-analysis demonstrates a significantly higher level of circulating PRL in RA patients when compared to healthy controls, and it was associated with region, age, measurement type and ESR.

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 <40 years, Asia group and disease duration <10 years had higher IL-8 levels., Conclusion: Compared with normal controls, circulating IL-8 levels in SLE patients are elevated and affected by age, region and disease duration.

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<30 years group had higher MMP-9 levels (SMD = 0.991, 95% CI: 0.504 to 1.478) and sample size (n ≥ 60) group had lower MMP-9 levels when compared with controls (SMD = -0.755, 95% CI: - 1.347 to -0.163)., 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)