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.

Global, regional and national temporal trends in prevalence for musculoskeletal disorders in women of childbearing age, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease Study 2019.

OBJECTIVES: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort. METHODS: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence (net drift, % per year), annual percentage change of prevalence within each age group (local drift, % per year), fitted longitudinal age-specific rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019. RESULTS: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift, higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts. CONCLUSIONS: Although a favourable overall temporal trend (net drift) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing.

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.

Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in women of childbearing age from 1990 to 2019.

AIM: To estimate the age-standardized incidence, prevalence, and mortality rates of autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), asthma, and psoriasis in women of childbearing age from 1990 to 2019, and to further analyze their changing trends, at global, regional, and national levels. METHODS: Women of childbearing age was defined as 15-49 years old. The estimates and 95% uncertainty intervals (UIs) for case number of RA, IBD, MS, T1DM, asthma and psoriasis in seven age groups (15-19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49 years) were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age standardization by direct method was adopted to estimate the age-standardized incidence, prevalence, and mortality rates of these autoimmune diseases in women of childbearing age. Joinpoint regression analysis was utilized to analyze the changing trends of estimated age-standardized incidence, prevalence, and mortality rates from 1990 to 2019 by calculating the average annual percentage change (AAPC) and its 95% confidence intervals (CIs). RESULTS: In 2019, the estimated global age-standardized incidence, prevalence, and mortality rates of RA in women of childbearing age was 17.13 (95% UI: 12.39 to 22.60), 215.86 (95% UI: 179.04 to 259.70), and 0.06 (95% UI: 0.04 to 0.08); of IBD was 5.85 (95% UI: 4.72 to 7.12), 63.54 (95% UI: 53.50 to 74.37), and 0.11 (95% UI: 0.08 to 0.13); of MS was 1.63 (95% UI: 1.05 to 2.28), 28.74 (95% UI: 23.80 to 34.46), and 0.17 (95% UI: 0.14 to 0.27); of T1DM was 6.22 (95% UI: 2.75 to 11.50), 290.51 (95% UI: 221.39 to 370.19), and 0.63 (95% UI: 0.48 to 0.78); of asthma was 291.14 (95% UI: 157.06 to 468.78), 2796.25 (95%UI: 1987.07 to 3842.97), and 1.42 (95% UI: 1.12 to 1.75), respectively. The estimated global age-standardized incidence and prevalence rates of psoriasis in women of childbearing age was 58.68 (95% UI: 51.04 to 66.85) and 477.20 (95% UI: 440.30 to 515.76). Highest disease burden generally exists in Region of the Americas and European Region. From 1990 to 2019, the estimated global age-standardized incidence and prevalence rates of RA (AAPC: 0.18, 95% CI: 0.11 to 0.24; AAPC: 0.24, 95% CI: 0.18 to 0.30) and T1DM (AAPC: 1.47, 95% CI: 1.40 to 1.54; AAPC: 0.83, 95% CI: 0.79 to 0.88) in women of childbearing age showed significantly increasing trends whereas those of IBD (AAPC: -0.76, 95% CI: -0.80 to -0.73; AAPC: -0.65, 95% CI: -0.70 to -0.60), MS (AAPC: -0.20, 95% CI: -0.23 to -0.16; AAPC: -0.25, 95% CI: -0.26 to -0.23), asthma (AAPC: -0.53, 95% CI: -0.60 to -0.47; AAPC: -0.74, 95% CI: -0.81 to -0.68), and psoriasis (AAPC: -0.83, 95% CI: -0.85 to -0.82; AAPC: -0.99, 95% CI: -1.02 to -0.96) showed significantly decreasing trends. Favorably, the estimated global age-standardized mortality rate of RA (AAPC: -1.32, 95% CI: -1.63 to -1.01), IBD (AAPC: -0.95, 95% CI: -1.06 to -0.84), MS (AAPC: -0.96, 95% CI: -1.12 to -0.80), T1DM (AAPC: -1.05, 95% CI: -1.21 to -0.89), and asthma (AAPC: -2.27, 95% CI: -2.34 to -2.19) in women of childbearing age all declined. The changing trends of estimated age-standardized incidence, prevalence, and mortality rates varied significantly across 204 countries and territories. CONCLUSIONS: Our study provides an accurate estimation on the age-standardization of disease indicators of autoimmune diseases in women of childbearing age. There are remarkable disparities in the incidence, prevalence, and mortality burden related to autoimmune diseases in women of childbearing age, as well as their changing trends across the world, suggesting that each individual government should establish flexible health policies and make reasonable source allocation to address different needs for autoimmune diseases in this population.

A global assessment of incidence trends of autoimmune diseases from 1990 to 2019 and predicted changes to 2040.

AIM: To analyze the global incidence trends for four autoimmune diseases (ADs) including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis from 1990 to 2019, and further predict their changes to 2040 at global, regional, and national levels. METHODS: The estimates and 95% uncertainty intervals (UIs) for case number and agestandardized incidence rate (ASIR) of RA, IBD, MS and psoriasis were derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Estimated annual percentage change (EAPC) was utilized to quantify the global incidence trends for RA, IBD, MS and psoriasis from 1990 to 2019. Furthermore, a log-linear age-period-cohort model was adopted to predict the new case number and incidence rates for these four ADs through 2040. RESULTS: From 1990 to 2019, the global ASIR rose significantly for RA (EAPC = 0.30%, 95% CI: 0.26 to 0.34) whereas declined significantly for IBD (EAPC = -0.60%, 95% CI: -0.72 to - 0.48), MS (EAPC = -0.19%, 95% CI: -0.24 to -0.13) and psoriasis (EAPC = -0.77%, 95% CI: -0.78 to -0.76). From 2020 to 2040, the global ASIR of RA, IBD, and psoriasis was predicted to decrease whereas the global ASIR of MS was predicted to increase, with continuous increasing case number of all these diseases. Furthermore, the predicted incidence trends of these four ADs varied significantly across 195 countries and territories, with a prominent higher burden in high-income North America and Western Europe. CONCLUSIONS: There are strong heterogeneities in the global incidence trends (1990-2019) and predicted changes (2020-2040) of ADs across the world, highlighting prominent challenges in the control of ADs, including both growing case number and distributive disparities of these diseases worldwide, which may be instructive for better public health policy establishment and healthcare resource allocation.

Climate change and daily outpatient visits for dermatomyositis in Hefei, China: a time-series study.

With the deepening of research on the correlation between meteorological factors and autoimmune diseases, the relationship between climate change and dermatomyositis (DM) has come to our attention. This study aimed to explore the short-term correlation between meteorological factors and DM outpatient visits. Daily records of hospital outpatient visits for DM, air pollutants, and meteorological factor data in Hefei from January 1, 2018 to December 31, 2021 were obtained. The mean temperature (MT), relative humidity (RH), diurnal temperature range (DTR), and temperature change between neighboring days (TCN) were used to quantify environmental temperature and humidity and their variations. And we performed a time series analysis using a generalized linear model (GLM) in combination with a distributed lag nonlinear model (DLNM). Furthermore, gender and age were further stratified for the analysis. The sensitivity analysis was also performed. A total of 4028 DM outpatient visits were recorded during this period. There were statistically significant associations of low temperature (5th, 1.5 °C), low RH (1st, 48.6%), high RH (99th, 99%), high DTR (75th, 12.6°c), and low TCN (10th, -2.7 °C) that were associated with risk of DM outpatient visits, with lag days of 30, 16, 16, 10, and 14, respectively. Moreover, women were more susceptible to high RH exposure and low TCN exposure, while the elderly were more susceptible to low temperature. This study concluded that exposure to low temperature, extreme RH, and temperature changes (especially high DTR and low TCN) was associated with an increased risk of DM outpatient visits.

The effect of air pollution exposure on the risk of outpatient visits for periodontitis: a time-series study.

This study aimed to determine if air pollution affected the risk of periodontitis outpatient visits. We collected the records of 56,456 periodontitis outpatient visits in Hefei, China, from January 1，2014 to December 31，2021. The relationship between air pollution and periodontitis outpatient visits was evaluated using distributed lag nonlinear and generalized linear models. Additional analyses were performed, stratifying the data by age, season, and sex. Subgroup analyses showed a significantly higher risk of periodontitis outpatient visits due to NO2 exposure during the warm season compared with the cold season. Moreover, O3 exposure was associated with a lower risk of periodontitis outpatient visits in the cold season. The findings suggest that NO2 exposure is associated with an increased risk of periodontitis outpatient visits, whereas O3 exposure is associated with a decreased risk of periodontitis outpatient visits. Season is found to be an effect modifier in these associations.

Association between short-term exposure to ambient air pollution and outpatient visits for pulpitis in Hefei, China: a time series study.

Evidence suggests a possible association between ambient air pollutants and oral diseases. Nevertheless, information regarding the relationship between air pollutants and pulpitis is scarce and inconclusive. In view of this, the present study aimed to investigate the relationship between short-term exposure to air pollution and outpatient visits for pulpitis. Daily data on outpatient visits for pulpitis, air pollutants, and meteorological data in Hefei, China, was collected from January 1, 2015 to December 31, 2021. The association between exposure to air pollutants and pulpitis outpatient visits was evaluated using distributed lag non-linear model (DLNM) and a generalized linear model (GLM). Furthermore, stratified analyses were performed by gender, age and season. A total of 93,324 records of outpatient visits for pulpitis were included in this study. The results showed that exposure to NO2, PM2.5, and CO were positively correlated with an increased risk of pulpitis outpatient visits. Each 10 µg/m3 increase in NO2 and PM2.5 concentration, at lag 0-2 day, was associated with a 2.4% (relative risk (RR) = 1.024, 95% confidence interval (CI): 1.014-1.035) and 0.5% (RR = 1.005, 95% CI: 1.000-1.010) increase in pulpitis outpatient visits, respectively. With a 1 mg/m3 increase in CO concentration, the risk of pulpitis outpatient visits increased by 9.1% (RR = 1.091, 95% CI: 1.031-1.154, lag 0-1 day). Intriguingly, exposure to O3 was associated with a decreased risk of pulpitis outpatient visits (RR = 0.990, 95% CI: 0.984-0.995, lag 0-5 day). Subgroup analysis revealed that in the warm season, exposure to PM2.5, O3, and CO was related with a significantly higher outpatient risk of pulpitis than in the cold season. Additionally, the influence of PM2.5 and CO exposure at age < 65 years was significantly stronger than at age ≥ 65 years. In conclusion, exposure to ambient NO2, PM2.5, and CO is associated with an increase in pulpitis outpatient visits in Hefei, China. Conversely, exposure to O3 reduces the risk of outpatient visits for pulpitis. Age and season are effect modifiers of these associations.

Association between air pollution exposure and outpatient visits for dermatomyositis in a humid subtropical region of China: a time-series study.

In recent years, a growing number of studies have found that air pollution plays critical roles in the onset and development of autoimmune diseases, but few studies have shown an association between air pollutants and dermatomyositis (DM). We sought to investigate the relationship between short-term exposure to air pollution and outpatient visits for DM and to quantify the burden of DM due to exposure to air pollutants in Hefei, China. Daily records of hospital outpatient visits for DM, air pollutants and meteorological factors data in Hefei from January 1, 2018 to December 31, 2021 were obtained. We used a distributed lag non-linear model (DLNM) in conjunction with a generalized linear model (GLM) to explore the association between air pollution and outpatient visits for DM, and conducted stratified analyses by gender, age and season. Moreover, we used attributable fraction (AF) and attributable number (AN) to reflect the burden of disease. A total of 4028 DM clinic visits were recorded during this period. High concentration nitrogen dioxide (NO2) exposure was associated with increased risk of DM outpatient visits (relative risk (RR) 1.063, 95% confidence interval (CI) 1.015-1.114, lag 0-5). Intriguingly, exposure to high concentration ozone (O3) was associated with reduced risk of outpatient visits for DM (RR 0.974, 95% CI 0. 0.954-0.993, lag 0-6). The results of stratified analyses showed that the cold season (vs. warm season) were more susceptible to outpatient visits for DM associated with NO2 and O3 exposure. In addition, we observed that an increased risk of DM outpatient visits was attributable to high concentration NO2 exposure, while high concentration O3 exposure was associated with a decreased risk of DM outpatient visits. This study provided a scientific basis for the etiology research and health protection of DM.

Global burden and cross-country inequalities in autoimmune diseases from 1990 to 2019.

AIM: To describe burden, and to explore cross-country inequalities across sociodemographic development levels for four autoimmune diseases (ADs) including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis (PS). METHODS: The estimates and their 95% uncertainty interval (UI) for disability-adjusted life-years (DALYs) of RA, IBD, MS and PS were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age-standardized DALYs rate (ASDR) across 204 countries, as well as age and sex distribution of global DALYs rate of these four ADs were illustrated. Slope index of inequality and concentration index, which are two standard metrics of absolute and relative gradient inequality recommended by World Health Organization (WHO), were utilized to quantify the distributive inequalities in the burden of ADs. RESULTS: In 2019, the ASDR of RA, IBD, MS and PS varied remarkably across 204 countries, with different age and sex distribution of global DALYs rate. The slope index of inequality changed from 26.7 (95% CI: 20.7 to 32.8) in 1990 to 40.3 (95% CI: 31.9 to 48.7) in 2019 for RA, from 17.1 (95% CI: 12.4 to 21.7) in 1990 to 25.2 (95% CI: 20.1 to 30.2) in 2019 for IBD, from 19.3 (95% CI: 15.2 to 23.4) in 1990 to 28.9 (95% CI: 24.2 to 33.5) in 2019 for MS, from 42.3 (95% CI: 33.1 to 51.6) in 1990 to 40.2 (95% CI: 32.5 to 48.0) in 2019 for PS. Moreover, the concentration index showed 20.4 (95% CI: 18.9 to 22.0) in 1990 and 18.2 (95% CI: 16.7 to 19.6) in 2019 for RA, 25.0 (95% CI: 23.0 to 27.1) in 1990 and 33.5 (95% CI: 31.6 to 35.5) in 2019 for IBD, 46.7 (95% CI: 44.0 to 49.3) in 1990 and 41.8 (95% CI: 39.6 to 44.1) in 2019 for MS, 31.7 (95% CI: 29.0 to 34.4) in 1990 and 32.6 (95% CI: 29.9 to 35.2) in 2019 for PS. CONCLUSIONS: There is a strong heterogeneity in ASDR across all countries, as well as in age and sex distribution of global DALYs rate for four ADs including RA, IBD, MS and PS. Countries with higher sociodemographic development levels shouldered disproportionately higher burden of ADs, and the magnitude of this sociodemographic development level-related inequalities exacerbated over time.

The effect of air pollution exposure on risk of outpatient visits for Sjogren's syndrome: A time-series study.

BACKGROUND: Emerging evidence showed that air pollutants are associated with development and recurrence of autoimmune disorders, but there is scarce evidence regarding the relationship between air pollutants and Sjogren's syndrome (SS). We sought to investigate whether air pollutants affect the risk of outpatient visits for SS and to quantify the burden of SS visits attributable to air pollution exposure in Hefei, China. METHODS: Daily data on outpatient visits for SS, air pollutants and meteorological data in Hefei, China, from January 1, 2015 to December 31, 2020 were obtained. A distributed lag non-linear model in conjunction with a generalized linear model were employed to assess the relationship between air pollution and SS outpatient visits. Stratified analyses were further performed by gender, age and season. Attributable fraction (AF) and attributable number (AN) were used to reflect disease burden. RESULTS: There were 4501 records of outpatient visits for SS. Exposure to PM2.5 was associated with increased risk of SS outpatient visits (relative risk (RR) = 1.218, 95% confidence interval (CI): 1.017-1.458, lag 0-14 day). An increase of 24 µg/m3 (interquartile range) in NO2 concentration was associated with 26.3% increase in the risk of SS outpatient visits (RR = 1.263, 95%CI: 1.105-1.445, lag 0-10 day). In contrast, exposure to O3 was associated with decreased risk of SS outpatient visits (RR = 0.692, 95%CI: 0.510-0.939, per 63 µg/m3 in O3 exposure, lag 0-27 day). Stratified analyses showed that females (vs. males) was more vulnerable to SS outpatient visits associated with NO2 and O3 exposure. SS patients aged ≥65 years (vs. aged <65 years) were susceptible to PM2.5 exposure. Exposure to PM2.5 or NO2 in the cold season was associated with higher risk of SS outpatient visits than that in the warm season. In addition, the AN (232, 95%CI: 119, 324) and AF (5.16%, 95%CI: 2.55%, 7.21%) of NO2 exposure were higher than those of PM2.5 exposure. CONCLUSION: PM2.5 and NO2 exposure are associated with increased risk of SS outpatient visits, while O3 exposure appears to be associated with decreased risk of SS outpatient visits. The effect of air pollutants exposure on risk of SS outpatients can be modified by age, gender and season. The burden of SS outpatient visits attributable to NO2 exposure is higher than those attributable to PM2.5 exposure.

Environmental factors and risk of gout.

Gout is a chronic disease with inflammatory arthritis caused by monosodium urate (MSU) crystals deposition, an elevated serum urate level (hyperuricaemia) is the critical factor leading to MSU crystals deposition and promoting the progression of gout. The onset and development of gout is generally the result of multiple factors, such as diet, heredity and environmental factors. Although genetics and diet are thought to play as major factors, a growing body of research evidence has highlighted that environmental factors also play a significant role in the onset and exacerbation of gout. Recent studies have shown that air pollutants such as particulate matter, sulfur dioxide (SO2) and carbon monoxide (CO) may increase the risk of hospitalizations for gout, and that the changes in temperature and humidity may affect uric acid (UA) levels. There is also seasonal trend in gout. It has been demonstrated that environmental factors may induce or accelerate the production and release of pro-inflammatory mediators, causing an unbalance oxidative stress and systemic inflammation, and then participating in the overall process or a certain link of gout. Moreover, several environmental factors have shown the ability to induce the production urate and regulate the innate immune pathways, involving in the pathogenesis of gout. Nevertheless, the role of environmental factors in the etiology of gout remains unclear. In this review, we summarized the recent literatures and aimed to discuss the relationship between environmental factors (such as microclimate, season, ambient/indoor air pollution and extreme weather) and gout. We further discussed the inflammatory mechanisms of environmental factors and gout and the comprehensive effects of environmental factors on gout. We also made a prospect of the management and treatment of gout, with special consideration to environmental factors associated with gout.

Genetically Predicted Circulating Omega-3 Fatty Acids Levels Are Causally Associated With Increased Risk for Systemic Lupus Erythematosus.

BACKGROUND: Accumulating evidence has demonstrated the associations of omega-3 or omega-6 polyunsaturated fatty acids (PUFAs) with the disease activity and inflammatory mediators of systemic lupus erythematosus (SLE), but the evidence of causal links of omega-3 or omega-6 PUFAs on the risk for SLE remains inconclusive. OBJECTIVES: This study was conducted to evaluate the causal relationships between omega-3/omega-6 PUFAs and SLE by performing the Mendelian randomization (MR) analysis. METHODS: Genome-wide significant single-nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) of circulating omega-3/omega-6 levels (n = up to 13,544) and GWAS meta-analyses of SLE (n = 14,267), respectively. The bidirectional two-sample MR (TSMR) analysis was conducted to infer the causality. RESULTS: The inverse-variance weighted (IVW) method revealed that genetically determined per SD increase in omega-3 levels were causally associated with an increased risk for SLE (odds ratios [ORs] = 1.49, 95% CI: 1.07, 2.08, p = 0.021), but no causal effect of omega-6 on the risk SLE was observed (IVW OR = 1.06, 95% CI: 0.72, 1.57, p = 0.759). In addition, there were no significantly causal associations in genetic predisposition to SLE with the changes of omega-3 and omega-6 levels, respectively (IVW beta for omega-3: 0.007, 95% CI: -0.006, 0.022, p = 0.299; IVW beta for omega-6: -0.008, 95% CI: -0.023, 0.006, p = 0.255). CONCLUSION: The present study revealed the possible causal role of omega-3 on increasing the risk for SLE, it could be the potential implications for dietary recommendations.

Association between meteorological factors and hospital admissions for uveitis in Hefei, China: a time-series study.

Meteorological variables are regarded as risk factors for inflammatory diseases, but their associations with uveitis, one of the leading causes accounting for blindness worldwide with an estimated prevalence of 38-714 cases/100,000 person-years, have not been thoroughly investigated. The present study explored the short-term association between meteorological variables and hospital admissions for uveitis in Hefei City, China. Daily data on uveitis hospital admissions and meteorological variables including mean temperature (MT) (°C), diurnal temperature range (DTR) (°C), and relative humidity (RH) (%), from 2014 to 2020, were collected. A time-series study using generalized linear model combined with distributed lag non-linear model was applied. Totally, 1911 admissions for uveitis including 894 first admissions and 1017 readmissions were reported during the study period. The associations of high percentile of MT (75th, 24.5℃) and low percentile of DTR (25th, 5.4℃) with uveitis admissions were observed to be statistically significant from lag9 (RR = 1.041, 95%CI: 1.002-1.081) to lag11 (RR = 1.053, 95%CI: 1.003-1.104) and lag4 (RR = 1.053, 95%CI: 1.019-1.088) to lag5 (RR = 1.052, 95%CI: 1.020-1.085), respectively. Moreover, a significant association between low percentile of RH (1th, 44%) and uveitis admissions appeared at lag0-8 (RR = 1.869, 95%CI: 1.017-3.434) and lasted until lag0-13 (RR = 2.539, 95%CI: 1.102-5.850) in the cumulative lag structure. Subgroup analyses indicated that males and the young seemed to be more sensitive to high MT exposure, while females appeared to be more vulnerable to low DTR exposure. Interestingly, both the young and the elderly are susceptible to low DTR and low RH exposure. Furthermore, high MT and low DTR exposure were associated with increased risk of first admission for uveitis. In summary, exposure to high-value of MT and low-value of DTR and RH may increase the hospital admissions for uveitis, especially for the status of first admission.

Therapeutic Potential of Galectin-1 and Galectin-3 in Autoimmune Diseases.

Galectins are a highly conserved protein family that binds to ß-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. They can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies have indicated that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. This information may provide a novel and promising therapeutic target for autoimmune diseases.

Association between non-optimal temperature and hospitalizations for gout in Anqing, China: a time-series analysis.

Previous studies have found that non-optimal temperature influences the development of gout, but the results have been inconsistent. The present study aimed to explore the effects of high temperature and high temperature variation on hospitalizations for gout in Anqing, China. We collected daily data on air pollutants, meteorological factors, and hospitalizations for gout between 1January 2016 and 31 December 2020 in Anqing City, China. We used Poisson generalized linear regression model and a distributed lag non-linear model (DLNM) to explore the relationship of high temperature, diurnal temperature range (DTR), and temperature change between neighboring days (TCN) with hospitalizations for gout. Stratified analysis by gender (male, female) and age (<65 years, ≥65 years) was conducted. Hospitalizations for gout attributed to high temperature, high DTR, and high TCN were also quantified. A total of 8675 hospitalized patients with gout were reported during the study period. We observed that exposure to high temperature was linked with an increased risk of hospitalizations for gout (lag 0, RR: 1.081, 95% confidence interval (CI): 1.011, 1.155). Exposure to high DTR was also associated with increased risk of hospitalizations for gout (lag9, RR: 1.017, 95% CI: 1.001,1.035). A large drop in temperature between neighboring days was associated an increased risk of hospitalizations for gout (lag 0-2 days, RR: 1.234, 95% CI: 1.017, 1.493). Stratified analysis results revealed that older adults and men were more sensitive to high-level DTR exposure than their counterparts. Nearly 15% of hospitalizations for gout could be attributable to high temperature (attributable fraction: 14.93%, 95% CI: 5.99%, 22.11%). This study suggests that high temperature and high temperature variation may trigger hospitalizations for gout, indicating that patients with gout need to take proactive actions in the face of days with non-optimal temperature.

Elevated Circulating Thrombomodulin Levels in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

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). CONCLUSION: 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.

Association between air pollution exposure and coronary heart disease hospitalization in a humid sub-tropical region of China: A time-series study.

Objective: Emerging evidence has highlighted the possible links of environmental pollution with several cardiovascular diseases (CVDs). The current study aimed to explore the impact of short-term air pollution exposure on CHD hospitalization in Hefei. Methods: Data about the daily number of CHD admissions (from 2014 to 2021) were retrieved from the First Affiliated Hospital of Anhui Medical University. Air pollutants and meteorological data were obtained from the China Environmental Monitoring Station and the China Meteorological Data Service Center, respectively. The correlation between air pollution and CHD hospitalization was assessed using distributed lag non-linear model (DLNM) and Poisson generalized linear regression. Results: In the single-pollutant model, NO2, O3, and CO strongly correlated with CHD hospitalization rate. Specifically, exposure to NO2 (lag0, relative risk [RR]: 1.013, 95%CI: 1.002-1.024, per 10 µg/m3 increase) and CO (lag13, RR: 1.035, 95%CI: 1.001-1.071, per 1 µg/m3 increase) revealed a positive correlation with an increased rate of CHD hospitalization. Interestingly, O3 had a protective association with hospitalization of CHD (lag0, RR: 0.993, 95%CI: 0.988-0.999, per 10 µg/m3 increase). Similar results, to those of the single-pollutant model, were revealed following verification using two-pollutant models. Subgroup analyses indicated that young people, women, and people in hot seasons were more susceptible to NO2 exposure, while the elderly, women, and people in cold seasons were more susceptible to O3. Furthermore, the elderly were more susceptible to CO exposure. Conclusion: Overall, exposure to NO2 and CO increases the rate of CHD hospitalization, but exposure to O3 shows a protective association with the rate of CHD hospitalization. Therefore, early preventive measures against air pollutants should be applied to protect vulnerable patients with CHD.

The Relationship Between Ambient Air Pollution and Hospitalizations for Gout in a Humid Subtropical Region of China.

OBJECTIVE: Gout is a chronic disease caused by the deposition of sodium urate (MSU) crystals. Available data on the association between environmental hazards and gout are scarce. The present study was present to investigate the relationship between short-term exposure to air pollution and hospitalizations for acute gout from 2016 to 2020 in Anqing City, China. METHODS: Daily records of hospital admissions for acute gout in Anqing from 1 January 2016 to 31 December 2020 were retrieved from the tertiary first-class hospitals in Anqing. Air pollutants and meteorological data were obtained from the China Environmental Monitoring Station and China Meteorological Data Service Center respectively. We used a time-series analysis to explore the association between air pollution (NO2, O3, and CO) and hospitalizations for acute gout, and conducted stratified analyses by gender, age and season. RESULTS: We observed an association between NO2 and hospitalizations for gout (lag 0, relative risk (RR):1.022, 95% confidence interval (CI):1.004-1.041). For every 1 mg/m3 increase in CO concentration, hospitalizations for gout increased by 3.9% (lag 11 days, RR=1.039, 95% CI: 1.004-1.076). Intriguingly, there was a negative association between O3 and hospitalizations for gout (lag0, RR=0.986, 95% CI: 0.976-0.996). Stratified analyses showed that exposure to high levels of NO2 was considered to be more vulnerable to gout in cold season. CONCLUSION: Our study showed that short-term exposure to NO2 and CO has a significant effect on hospitalizations for acute gout.