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.

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.

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.

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.

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.

Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study.

The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk.

[Relation of miR-140 Expression Level with Therapeutic Effect of Decitabine and Its Mechanism].

OBJECTIVE: To investigate the relationship of miR-140 expression level with the therapeutic effect of decitabine, and to explore whether the molecular mechanism is dependent on the regulation of TLR4 expression. METHODS: Forty-seven patients with acute myeloid leukaemia (AML) were enrolled in our study and divided into decitabine combination treatment group (22 cases) and traditional treatment group (25 cases). The clinical efficacy was compared between these two groups. Real-time PCR was used to determine the plasma level of miR-140 in AML patients. Decitabine, miR-140 mimic and miR140 inhibitor were used to treat AML HL-60 cells in vitro, the real-time PCR and Western blot were used to detect the expressions of miR-140, TLR4 and NF-κB at both mRNA and protein levels. RESULTS: Compared with traditional treatment group, decitabine combination treatment group showed more significant clinical efficacy. Plasma miR-140 level in both 2 treatment groups both decreased, but the plasma miR-140 level was higher in decitabine combination treatment group as compared with traditional treatment group. Experiment in vitro showed that 0.3 µmol/L decitabine significantly inhibited the HL-60 cell proliferation accompanied by up-regulation of miR-140 expression and down-regulation of expression of TLR4 and NF-κB. These effects induced by decitabine were partly reversed by pretreating the cells with 200 nmol/L miR-140 inhibitor. CONCLUSION: Decitabine-induced up-regulation of miR-140 expression may be related with its chemotherapeutic effects, and miR-140/TLR4/NF-κB pathway may partly mediate the pharmacologic action of decitabine.

TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo.

The aim of the present study was to investigate the radiosensitization effect of triciribine (TCN) on human esophageal squamous cell carcinoma (ESCC) in normoxia or hypoxia and its mechanism. The cytotoxicity and radiosensitization mechanism of TCN were investigated by Cell Counting Kit 8, clonogenic assay, flow cytometry, western blotting (WB) and immunofluorescence staining of phospho-histone H2A.X, Ser139 (γ-H2AX) in ESCC in vitro, while the protein expression levels of AKT, phosphorylated (p)-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were evaluated by WB in vivo. The cytotoxicity of TCN was dose dependent. Upon exposure to TCN, ESCC cells in hypoxia treated with 4-Gy radiotherapy exhibited an evidently higher apoptotic rate than cells subjected to other treatments. TCN could significantly inhibit the protein expression of p-AKT, HIF-1α and VEGF in vitro and in vivo. The present results suggested that TCN can effectively inhibit AKT, p-AKT, HIF-1α and VEGF, thus conferring radiosensitivity to ESCC in vitro and vivo. TCN is considered as an adjuvant in radiotherapy of ESCC in clinical application.

Microarray expression profile analysis of aberrant long non-coding RNAs in esophageal squamous cell carcinoma.

Increasing evidence indicates that long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the function and regulatory mechanism of lncRNAs are still unclear in esophageal squamous cell carcinoma (ESCC). To address this challenge, we screened lncRNAs expression profiles in 3 pairs of ESCC and matched non-cancerous tissues by microarray assay and identified the relationship between lncRNAs expression in ESCC tissue and clinicopathological characteristics and prognosis of patients with ESCC. We found 182 lncRNAs that were significantly differently expressed in ESCC tissues versus the matched non-cancerous tissues. Gene ontology and pathway analysis results suggested that the primary biological processes of these genes were involved in extracellular matrix, immune responses, cell differentiation and cell proliferation. Through cis and trans analyzing, we found 4 lncRNAs (ENST00000480669, NONHSAT104436, NONHSAT126998 and NONHSAT112918) may play important roles in tumorigenesis of ESCC. The four lncRNAs were checked in 73 patients with ESCC. The results showed that they mainly related to tumor metastasis. Kaplan-Meier survival analysis showed that high expression of NONHSAT104436, NONHSAT126998 and low expression of ENST00000480669 were related to poor 3-year overall survival (P=0.003, 0.032 and 0.040, respectively). Multivariate analysis showed that NONHSAT104436 was an independent prognostic factor (P=0.017). Thus we concluded that, lncRNAs showed differently expression patterns in ESCC versus matched non-cancerous tissues, and aberrantly expressed lncRNA may play important roles in ESCC development and progression. Interestingly, the overexpression of NONHSAT104436 was tightly correlated with distant metastasis and, poor survival rate, which might indicate that NONHSAT104436 might play a very important part in ESCC tumor progression.

VEGF +405G/C (rs2010963) polymorphisms and digestive system cancer risk: a meta-analysis.

Vascular endothelial growth factor (VEGF) polymorphisms, specifically +405G/C (rs2010963), reportedly influence the risk for various digestive cancers. However, the consequences of these polymorphisms remain controversial and ambiguous. Therefore, we performed a meta-analysis of 11 studies with VEGF +405G/C genotyping on 2,862 patients and 3,028 controls using the random effects model. We obtained a pooled odds ratio (OR) of 1.04 (95% confidence interval (CI) = 0.86-1.26) for the recessive genetic model, 1.07 (95% CI = 0.81-1.42) for the dominant genetic model, 1.09 (95% CI = 0.81-1.47) for the homozygote comparison, and 1.03 (95% CI = 0.83-1.27) for the heterozygote comparison. In the subgroup analysis of the recessive model, the OR was 1.20 (95% CI = 1.02-1.40) in colorectal cancer. These results show that VEGF +405G/C polymorphisms are unlikely to be a major determinant of susceptibility to digestive cancer. Furthermore, the subgroup analysis of recessive model indicates that VEGF +405G/C polymorphisms increase the risk for colorectal cancer.