Associations between air pollutants and acute exacerbation of drug-resistant tuberculosis: evidence from a prospective cohort study.

BACKGROUND: Short-term exposure to air pollution may trigger symptoms of drug-resistant tuberculosis (DR-TB) through stimulating lung tissue, damaging tracheobronchial mucosa, the key anti-mycobacterium T cell immune function, and production and release of inflammatory cytokines. OBJECTIVE: To investigate the association between acute exacerbations of DR-TB and short-term residential exposure to air pollutants (PM10, PM2.5, SO2, NO2, CO and O3) based on a large prospective cohort in Anhui Province, China. METHOD: Patients were derived from a prospective cohort study of DR-TB in Anhui Province. All DR-TB patients underwent drug-susceptibility testing and prefecture-level reference laboratories confirmed their microbiologies. The case-crossover design was performed to evaluate the association between the risk of acute exacerbations of DR-TB and short-term residential exposure to air pollution. RESULTS: Short-term NO2 exposure was significantly related to an elevated risk of first-time outpatient visit due to acute exacerbations of DR-TB(relative risk:1.159, 95% confidence interval:1.011 ~ 1.329). Stratification analyses revealed that the relationship between the risk of acute exacerbations and NO2 exposure was stronger in the elderly (age ≥ 65) DR-TB patients, and in individuals with a history of TB treatment. CONCLUSIONS: NO2 Exposure was significantly associated with an elevated risk of acute exacerbation of DR-TB in Anhui Province, China.

Hormonal and reproductive factors in relation to the risk of rheumatoid arthritis in women: a prospective cohort study with 223 526 participants.

OBJECTIVE: This study aimed to examine rheumatoid arthritis (RA) risk associated with hormonal and reproductive factors in women from the large cohort of the UK Biobank. METHODS: Data on hormonal and reproductive factors in women were collected from a prospective cohort of 223 526 UK Biobank participants. The potential relationship between reproductive factors and RA risk was assessed using restricted cubic spline. Hazard ratios (HR) were estimated using Cox proportional hazard regressions. RESULTS: During a median follow-up of 12.39 years, 3313 women with RA were identified. Age at menarche >14 years was associated with a greater RA risk (HR 1.13, 95% CI 1.02 to 1.26) compared with menarche at 13. The multiple adjusted HR for RA in women with menopause at <45 years was 1.46. Reproductive years <33 increased the risk of RA (HR 1.39, 95% CI 1.21 to 1.59). Compared with those with 2 children, women with ≥4 children were associated with a higher risk of RA (HR 1.18, 95% CI 1.04 to 1.34). Women who had a hysterectomy (HR 1.40, 95% CI 1.25 to 1.56) or oophorectomy (HR 1.21, 95% CI 1.08 to 1.35) had a higher risk of RA than those without a hysterectomy or oophorectomy. Both hormone replacement therapy (HRT) use (HR 1.46, 95% CI 1.35 to 1.57) and HRT duration (HR 1.02, 95% CI 1.01 to 1.03) were associated with a higher risk of RA. CONCLUSIONS: Some hormonal and reproductive factors were associated with a higher risk of RA. Hormonal and reproductive factors should be considered in risk assessment and formulating management plans in female patients with RA.

Serum albumin mediates the associations between heavy metals and two novel systemic inflammation indexes among U.S. adults.

BACKGROUND: The effects of heavy metal exposure on immunological function have sparked widespread concern, but unequivocal evidence on the association between mixed metal exposure and novel systemic inflammatory indexes remains scarce. OBJECTIVES: This study aimed to analyze the associations of heavy metals with two novel systemic inflammation indexes and the mediated effects of serum albumin. METHODS: Nineteen metals were detected among 4082 U.S. adults based on the NHANES. A linear regression, restricted cubic splines (RCS) regression, weighted quantile sum (WQS), Quantile-based Gcomputation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted to evaluate the associations of single metal and mixed metals with systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) levels, respectively. A series of subgroup analyses were used to identify potentially vulnerable populations. Furthermore, we conducted mediation analyses to investigate the mediated effects of serum albumin on the associations of metals with SII and SIRI. RESULTS: In the single-exposure model, exposure to various metals such as urinary Co, As, and serum Zn, Cu was associated with SII and SIRI (PFDR<0.05). Simultaneously, the above metals were linear positively correlated with SII and SIRI. Mixed-exposure analyses consistently showed that overall mixed urinary metal levels were positively pertinent for SII and SIRI levels, and the metal Co played a significant role in the urinary metal mixtures. Subgroup analyses showed that exposure to urinary Cd in men and elderly people increased SII and SIRI levels. The results of mediation analyses suggested the association of urinary metal mixture with SII and SIRI was mediated by albumin, and the proportion of mediation was 14.45% and 9.49%, respectively. CONCLUSIONS: Our findings suggested that metal exposure is strongly associated with the levels of system inflammation indexes and that serum albumin is, in part, a mediator of this association.

Impact of short-term exposure to ambient air pollution on osteoarthritis: a multi-city time-series analysis in Central-Eastern China.

Osteoarthritis (OA) is a threat to public health issue with high morbidity and disability worldwide. However, unequivocal evidence on the link between air pollution and OA remains little, especially in multi-study sites. This study aimed to explore the relationship between short-term exposure to main air pollutants and the risk of OA outpatient visits in multi-study sites. A multi-city time-series analysis was performed in Anhui Province, Central-Eastern China from January 1, 2015, to December 31, 2020. We used a two-stage analysis to assess the association between air pollution and daily OA outpatient visits. City-specific associations were estimated with a distributed lag nonlinear model and then pooled by random-effects or fixed-effects meta-analysis. Stratified analysis was conducted by gender, age, and season. Additionally, the disease burden of OA attributable to air pollutant exposure was calculated. A total of 35,700 OA outpatients were included during the study period. The pooled exposure-response curves showed that PM2.5 and PM10 concentrations below the reference values could increase the risk of OA outpatient visits. Concretely, per 10 ug/m3 increase in PM2.5 concentration was linked to an elevated risk of OA outpatient visits at lag 2 and lag 3 days, where the effect reached its highest value on lag 2 day (RR: 1.023, 95%CI: 1.005-1.041). We observed that a 10 µg/m3 increase in PM10 was positively correlated with OA outpatient visits (lag2 day, RR: 1.011, 95%CI: 1.001-1.025). Nevertheless, no statistical significance was discovered in gaseous pollutants (including SO2, O3, and CO). Additionally, a significant difference was found between cold and warm seasons, but not between different genders or age groups. This study reveals that particulate matter is an important factor for the onset of OA in Anhui Province, China. However, there is no evidence of a relationship of gaseous pollutants with OA in this area.

Increased circulating sclerostin levels in rheumatoid arthritis patients: an updated meta-analysis.

BACKGROUND: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/ß-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.

Association of PER2 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

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.

Low ambient temperature increases hospital re-admissions for systemic lupus erythematosus in humid subtropical region: a time series study.

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.

Association between traffic-related air pollution and hospital readmissions for rheumatoid arthritis in Hefei, China: A time-series study.

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.

Circulating Meteorin-like Levels in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis.

BACKGROUND: Meteorin-like (Metrnl) is a newly identified adipokine implicated in the pathogenesis of type 2 diabetes mellitus (T2DM), yet data on the circulating levels of Metrnl in patients with T2DM are controversial. To derive a more precise estimation on circulating Metrnl levels in T2DM patients, we conducted this meta-analysis. METHODS: The existing studies on the circulating levels of Metrnl in patients with T2DM published up to 16 January 2020 were comprehensively retrieved from PubMed, Web of Science, EMBASE, and The Cochrane library database. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated using random-effects model. Heterogeneity was assessed and quantified by Cochrane's Q and I2 statistic. All statistical analyses were performed using Stata 12.0 software. RESULTS: Nine studies with 867 T2DM patients and 831 normal glucose tolerance (NGT) controls were included in the final analysis according to the inclusion criteria. No significant difference in circulating Metrnl levels was found between T2DM patients and NGT individuals (pooled SMD = -0.429, 95% CI = -1.077 to 0.219). Compared to controls, circulating Metrnl levels were significantly higher in the subgroups with BMI <25 kg/m2, using plasma sample and patient sample size ≥100, while circulating Metrnl levels were significantly lower in subgroups with age ≤50 years and homeostatic model assessment for insulin resistance (HOMA-IR) ≥4. CONCLUSION: This meta-analysis indicates no significant change in circulating Metrnl levels in T2DM patients. However, this result may be influenced by age, BMI, sample type, HOMA-IR and patients sample size. Further longitudinal studies are warranted to offer more insights into the relationship between Metrnl and T2DM.

Mortality and Disease Burden of Injuries from 2008 to 2017 in Anhui Province, China.

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.

Association of Midkine and Pleiotrophin Gene Polymorphisms With Systemic Lupus Erythematosus Susceptibility in Chinese Han Population.

In a previous study, we have reported an increased plasma midkine (MK) and pleiotrophin (PTN) concentrations in patients with systemic lupus erythematosus (SLE) and the increase in MK and PTN associated with inflammatory cytokines interleukin (IL)-17 level and some clinical manifestations, suggesting the underlying association of MK and PTN with SLE. This study was conducted to investigate the association between common single-nucleotide polymorphisms (SNPs) in the MK and PTN gene and SLE susceptibility. A total of 989 subjects (496 SLE patients and 493 healthy controls) were included and genotyped for three MK SNPs and seven PTN SNPs in using improved multiple ligase detection reaction (iMLDR). Results have demonstrated no significant differences for genotype and allele frequencies in all 10 SNPs between SLE patients and healthy controls. Case-only analysis in SLE revealed that, in MK gene, the genotype frequency of AA/AG (rs35324223) was significantly lower in patients with photosensitivity than those without; the allele frequency of A/G (rs20542) was significantly higher in patients without serositis. In PTN gene, the A/G allele frequency (rs322236), C/T allele frequency, and TT/CT genotype frequency (rs6970141) showed significantly increased results in patients with immunological disorder compared to those without. Furthermore, no significant differences in plasma MK and PTN concentrations with its SNPs genotypes were found. MK and PTN SNPs showed no associations with SLE genetic susceptibility, but it may be associated with the course of this disease; further studies are needed to focus on the mechanism of MK and PTN genes in the pathogenesis of SLE.

Decreased Expression of Semaphorin 3A and Semaphorin 7A Levels and Its Association with Systemic Lupus Erythematosus.

A growing body of data suggests that semaphorins are involved in both normal and pathological immune responses, as well as autoimmune pathologies. To investigate the plasma semaphorin 3A (Sema3A) and semaphorin 7A (Sema7A) levels in systemic lupus erythematosus (SLE) patients and their correlation with clinical manifestations and laboratory indexes, a two-step method was applied. First, 80 SLE patients and 80 healthy controls were recruited for comparing serum Sema3A and Sema7A concentrations. Second, 40 rheumatoid arthritis (RA) patients and 40 sjögren's syndrome (SS) patients were then included as disease controls. Plasma Sema3A and Sema7A concentrations were detected by ELISA. There were significant differences in Sema3A and Sema7A among four groups. When compared to healthy controls, both Sema3A and Sema7A levels were decreased in SLE and increased in RA; increased Sema3A level and decreased Sema7A level were found in SS. There were significant differences in Sema3A concentration between SLE and RA, SLE and SS. Moreover, there were significant differences in Sema7A level between SLE and RA, SS and RA. However, no significant differences in Sema3A between SS and RA and no significant differences in Sema7A between SS and SLE were observed. Both plasma Sema3A and Sema7A levels were correlated with anti-SSA and IgM. Area under curve (AUC) of the receiver operating characteristic (ROC) curve for Sema3A and Sema7A were 0.535 (0.455-0.613) and 0.671 (0.594-0.742), respectively. Aberrant Sema3A and Sema7A expression and their clinical associations in SLE suggest their important role in this disease.

Seasonality and global public interest in psoriasis: an infodemiology study.

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.

Elevated Circulating Interleukin-17 Levels in Patients with Systemic Lupus Erythematosus: A Meta-analysis.

BACKGROUND: Previous studies concerning the circulating interleukin-17 (IL-17) in systemic lupus erythematosus (SLE) were contradictory. AIMS: To further precisely investigate circulating IL-17 in SLE and evaluate its influential factors by meta-analysis. METHODS: EMBASE, PubMed and Cochrane Library were comprehensively searched to obtain studies on circulating IL-17 in SLE patients by November 22, 2018. The results were illustrated by pooled standard mean difference (SMD) with corresponding 95% confidence interval (CI) using random-effects model as there was significant heterogeneity, which was estimated using Cochran Q and I2 statistics. Subgroup analyses and sensitivity analyses were also conducted. RESULTS: Overall, 1872 articles were reviewed and 20 studies involving 1067 subjects with SLE and 721 healthy controls (HCs) were enrolled in the final analysis according to inclusion criteria. Compared with HCs, circulating IL-17 levels in SLE patients were elevated (SMD: 1.183, 95% CI: 0.763-1.603; P < .001). Moreover, in comparison to HCs, European and Asian SLE patients, age <30 years, disease duration ≥5 years, NOS scores <7 and using ELISA showed increased circulating IL-17 status, whereas no significant change was observed in other subgroups. There was no significant publication bias. Sensitivity analyses demonstrated that the results of our meta-analysis were robust. CONCLUSIONS: SLE patients have higher circulating IL-17 levels, which is influenced by ethnic, age and disease duration, literature quality and measurements.

Association of Melatonin Pathway Gene's Single-Nucleotide Polymorphisms with Systemic Lupus Erythematosus in a Chinese Population.

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.

Circulating pentraxin-3 levels in patients with systemic lupus erythematosus: a meta-analysis.

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.

Association between circulating 25-hydroxyvitamin D and systemic lupus erythematosus: A systematic review and meta-analysis.

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 (I2 ) 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.

Plasma galectin-3 levels do not differ in systemic lupus erythematosus patients.

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.

Potential role of melatonin in autoimmune diseases.

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-1ß 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.