Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

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.

Dickkopf-1 as a promising therapeutic target for autoimmune diseases.

Dickkopf-1 (DKK-1) is mostly known as a mature inhibitor of classic Wnt signaling pathways, which plays a critically role in regulating bone formation and bone metastasis. In recent years, the roles of DKK-1 played in bone resorption, bone formation, immune homeostasis and inflammation have been investigated. The role of DKK-1 in the pathogenesis and treatment of autoimmune diseases (ADs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), etc, has attracted widespread attention. Various studies have found that DKK-1 may be used as a biomarker for the occurrence and development of ADs, and as a potential target for the treatment of ADs. In this review, we have briefly summed up the intricate immunological functions and regulatory mechanisms of DKK-1 in ADs, aiming to further learning more about the role of DKK-1 involved in the pathogenesis of ADs and provide an outlook for the potential future researches.

COVID-19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

Leveraging Google Trends to investigate the global public interest in rheumatoid arthritis.

This study aims to investigate the global public interest in rheumatoid arthritis by evaluating search term popularity changes of the disease over a decade. Google Trends was applied to retrieve search popularity scores for the term 'rheumatoid arthritis' between January 2004 and December 2017, utilizing the category of "health". Overall, relative searches volume for rheumatoid arthritis steadily decreased from January 2004 to December 2010, and then slowly rose from January 2011 to December 2017. There were significant seasonal variations in relative searches volume for the term 'rheumatoid arthritis' (Amplitude = 3.11; Phase: Month = 4.3; Low point: Month = 10.3; p < 0.025). Relative searches volume peaked in April and reached the lowest level in October. The top 11 rising topics were scleroderma, Anna Marchesini, C-reaction protein, osteoarthritis, arthritis, joint pain, autoimmune disease, rheumatoid factor, rheumatology, methotrexate, and systemic lupus erythematosus, ranking from high to low by relative growth of topic regarding rheumatoid arthritis. In conclusion, the evidence from Google Trends analysis demonstrates a significant seasonal variation in rheumatoid arthritis, with a peak in April. In addition, the top rising search queries are beneficial for physicians to search the Internet themselves for websites that provide high-quality information to recommend to their patients.

Circular RNA expression profile and potential function of hsa_circ_0045272 in systemic lupus erythematosus.

Circular RNAs (circRNAs) represent a class of non-coding RNAs that form covalently closed RNA circles with extensive expression and conservation in mammals. Circular RNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases, but studies of circRNA role in systemic lupus erythematosus (SLE) are lacking. The present study measured the circRNA expression profiles in T cells from patients with SLE and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients. Down-regulation of hsa_circ_0045272 in SLE T cells was verified with quantitative PCR. Jurkat cells with stable hsa_circ_0045272 knockdown were generated using specific lentiviral short hairpin RNA for functional studies. Flow cytometric analysis indicated that hsa_circ_0045272 knockdown significantly up-regulated the early apoptosis of Jurkat cells. Meanwhile, ELISA showed that hsa_circ_0045272 knockdown significantly enhanced interleukin-2 production of activated Jurkat cells. Then, ceRNAs were predicted for hsa_circ_0045272 and the significant down-regulation of two mRNAs predicted as ceRNAs, NM_003466 (PAX8) and NM_015177 (DTX4), but not their corresponding proteins, was validated. Furthermore, dual luciferase reporter assay indicated binding of hsa_circ_0045272 with hsa-miR-6127. Circular RNA-mRNA co-expression networks showed the correlation of circRNAs with mRNAs and provided additional clues to circRNA functions. Our study demonstrated dysregulated circRNAs in SLE and revealed the function of hsa_circ_0045272 in negatively regulating apoptosis and interleukin-2 secretion and its potential mechanism. The implication of hsa_circ_0045272 and other abnormal circRNAs in SLE merits further investigation.

Exposure to Radon and Kidney Cancer: A Systematic Review and Meta-analysis of Observational Epidemiological Studies.

OBJECTIVE: To evaluate the possible association between radon exposure and kidney cancer. METHODS: We performed a systematic review and a meta-analysis based on random effect models to provide a pooled association measure. RESULTS: We subjected 8 studies (overall relative risks and 95% confidence intervals: 1.01, 0.72 to 1.43, I2 = 64.4%) to meta-analysis. Subgroup analysis revealed a marginally significant association between radon exposure and kidney cancer in studies conducted in Europe. Two population-based studies provided no evidence for the increased risk of kidney cancer in the general population. CONCLUSION: The association between radon and kidney cancer remains unclear but cannot be excluded because of its biological plausibility and the limited number and quality of existing studies. Additional data from the general population and well-designed miner cohort studies are needed to reveal the real relationship between radon exposure and kidney cancer.

Comprehensive long non-coding RNA expression profiling reveals their potential roles in systemic lupus erythematosus.

Long non-coding RNAs can regulate gene transcription, modulate protein function, and act as competing endogenous RNA. Yet, their roles in systemic lupus erythematosus remain to be elucidated. We determined the expression profiles of lncRNAs in T cells of SLE patients and healthy controls using microarrays. Up to 1935 lncRNAs and 1977 mRNAs were differentially expressed. QRT-PCR showed downregulated uc001ykl.1 and ENST00000448942 in SLE patients. Expression of uc001ykl.1 correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein, whereas ENST00000448942 level correlated with ESR and anti-Sm antibodies. Short time-series expression miner analysis revealed some lncRNAs whose expressions might correlate with disease activity of SLE patients. Coding-non-coding gene coexpression analyses showed differential lncRNAs might operate via modulating expressions of their correlated, relevant mRNAs in SLE. Differential lncRNAs might also function through their ceRNAs. Our study established that the aberrant expression profiles of lncRNAs may play a role in SLE and thus warrant further investigation.

Evidence of epistatic interaction between DPP4 and CCR6 in patients with rheumatoid arthritis.

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

Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to Rheumatoid Arthritis: A Meta-Analysis.

OBJECTIVE: Association of matrix metalloproteinases (MMPs) gene polymorphisms with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify this dispute. METHODS: We systematically searched the electronic PUBMED, EMBASE and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9) gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to the heterogeneity, fixed-effects or random-effects models were used to calculate crude odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 11 articles involving 2143 cases and 2049 controls were included in this meta-analysis. Overall, no significant associations were observed between MMP-1-1607 1G/2G polymorphism and RA. Stratification by ethnicity, no significant associations were observed in Caucasian populations. Similarly, no significant associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms and RA in overall and Caucasian populations, respectively. However, a weak association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR = 0.813, 95%CI = 0.694-0.953, p = 0.010) in overall populations. CONCLUSIONS: The present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP-2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with more sample size are needed for definitive conclusions.

Increased serum visfatin level is associated with fat deposition of the lumbar spine in ankylosing spondylitis patients.

Objectives: To assess the serum visfatin levels in patients with ankylosing spondylitis (AS), as well as its correlation with fat deposition of the lumbar spine. Methods: Serum visfatin levels were detected by enzyme-linked immunosorbent assay (ELISA) in 50 AS patients and 75 sex-and age-matched healthy controls. The clinical and laboratory indexes of AS patients were recorded, and the lumbar spine magnetic resonance scan was performed to evaluate the lumbar spine fat deposition in AS patients. The level of serum visfatin and its correlation with lumbar fat deposition were analyzed, and the risk factors of AS lumbar MRI fat deposition were evaluated by Logistic regression. Results: Serum visfatin levels in AS patients were elevated compared with that in healthy controls (p < 0.001), and were more significant in patients with fat deposition and syndesmophyte formation (p = 0.017 and p = 0.014, respectively). Serum visfatin levels were positively correlated with CRP, BASDAI, mSASSS and fat deposition (all p < 0.05). Age (OR = 1.085, 95% CI: 1.005-1.173, p = 0.038), disease duration (OR = 1.267, 95% CI: 1.017-1.578, p = 0.035), and visfatin (OR = 1.846, 95% CI: 1.004-3.393, p = 0.048) were risk factors for fat deposition in AS patients. Conclusions: The level of serum visfatin in AS patients is significantly increased, which is associated with fat deposition on lumbar MRI. Elevated visfatin level is an independent risk factor for AS lumbar fat deposition.

Two Decades of Publications in Journals Dedicated to Autoimmunity: A Bibliometric Analysis of the Autoimmunity Field from 2004 to 2023.

To carry out an in-depth analysis of the scientific research on autoimmunity, we performed the first bibliometric analysis focusing on publications in journals dedicated to autoimmunity (JDTA) indexed by science citation index during the period 2004-2023. Using bibliometric analysis, we quantitatively and qualitatively analyzed the country, institution, author, reference and keywords information of publications in JDTA, so as to understand the quantity, publication pattern and publication characteristics of these publications. The co-occurrence networks, clustering map and timeline map were created by CiteSpace and VOSviewer software to visualize the results. The CiteSpace was also used to analyze the strongest citation burst of keywords, which could describe the frequency, intensity and time period of high-frequency keywords, and indicate the research hotspots in the field. A total of 5 710 publications were analyzed, and their annual distribution number was basically stable from 2004 to 2023, fluctuating around 300. The United States and Italy led the way in terms of the number of publications, followed by France and China. For international cooperation, the developed countries represented by the United States cooperate more closely, but the cooperation was localized, reflecting that there was no unified model of autoimmunity among countries. UDICE-French Research Universities had the greatest number of publications. Subsequently, the number of publications decreased slowly with the ranking, and the gradient was not large. Eric Gershwin and Yehuda Shoenfeld stood out among the authors. They had an excellent academic reputation and great influence in the field of autoimmunity. The results of keyword analysis showed that JDTA publications mainly studied a variety of autoimmune diseases, especially SLE and RA. At the same time, JDTA publications also paid special attention to the research of cell function, autoantibody expression, animal experiments, disease activity, pathogenesis and treatment. This study is the first to analyze the publications in JDTA from multiple indicators by bibliometrics, thus providing new insights into the research hotspots and development trends in the field of autoimmunity.

Mendelian Randomization Analysis of Circulating Cytokines and Risk of Autoimmune Neuroinflammatory Diseases.

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

Time Trends in the Burden of Environmental Heat and Cold Exposure Among Children and Adolescents.

Importance: Environmental heat and cold exposure (EHCE) remains the principal preventable cause of morbidity and mortality in children and adolescents globally. Objective: To report EHCE-related burden and analyze its temporal trends among children and adolescents from 1990 to 2019. Design, Setting, and Participants: This repeated cross-sectional study used data from the Global Burden of Disease Study 2019, which encompassed 204 countries and territories from 1990 to 2019. Children and adolescents aged 0 to 19 years were included in the study. Data analysis occurred from December 2023 to March 2024. Exposure: EHCE in children and adolescents from January 1990 to December 2019. Main Outcomes and Measures: The primary outcomes were cases and rates of EHCE incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and average annual percentage changes (AAPCs). Global trends in these metrics were also analyzed by sex, age, and sociodemographic index (SDI), which is a comprehensive indicator of the socioeconomic status of a country or region. A linear regression model was used to calculate AAPCs and a joinpoint regression model was used to identify the years in which trends changed significantly. Results: From 1990 to 2019, EHCE-related incidence, prevalence, mortality, and DALYs showed a downward trend globally. However, an upward trend in EHCE incidence and prevalence was detected between 2010 and 2019 (incidence AAPC, 1.46; 95% CI, 1.05-1.87; prevalence AAPC, 1.25; 95% CI, 1.01-1.50). Regionally, although EHCE-related incidence showed a decreasing trend in most regions from 1990 to 2019, there were still some regions with an increasing trend (Southern sub-Saharan Africa AAPC, 0.23; 95% CI, 0.01-0.44). In 2019, the mortality and DALYs of EHCE were higher among children and adolescents in countries with low SDI levels. Additionally, the burden of EHCE among children and adolescents varied according to sex and age. Conclusions and Relevance: In this cross-sectional study, a global increase was observed in EHCE incidence and prevalence since 2010. Furthermore, children and adolescents in low-SDI regions, which bear the brunt of the climate crisis, were disproportionately impacted. This suggests that future responses to climate change crises should emphasize health equity, which implies that vulnerable populations, such as children and adolescents, should be given priority in the allocation of resources to address climate change.

Serum DKK-1 level in ankylosing spondylitis: insights from meta-analysis and Mendelian randomization.

Objective: The purpose of this study was to precisely evaluate the serum Dickkopf-1 (DKK-1) level in patients with ankylosing spondylitis (AS) relative to that in normal controls and to test the causal relationship between DKK-1 and the risk of AS. Methods: Embase, PubMed, Web of Science, WANFANG DATA, VIP, and China National Knowledge Infrastructure (CNKI) were comprehensively searched until July 2022 for pertinent studies. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated by the fixed or random-effect model. In Mendelian randomization (MR) analysis on the causal relationship between serum DKK-1 level and AS risk, the inverse variance weighting method (IVW), MR-Egger regression, weighted median method, and weighted pattern method were applied. Sensitivity analyses, including the horizontal pleiotropy test, heterogeneity test, and leave-one-out test, were also performed. Results: The meta-analysis of 40 studies containing 2,371 AS patients and 1,633 healthy controls showed that there was no significant difference in DKK-1 serum level between AS patients and normal controls (pooled SMD=0.207, 95% CI =-0.418-0.832, P=0.516). The subgroup analysis of the CRP ≤ 10 mg/L group showed that AS patients had higher serum DKK-1 concentration than the healthy controls (SMD=2.267, 95% CI = 0.102-4.432, P=0.040). Similarly, MR analysis also demonstrated no significant association between DKK-1 serum level and AS (IVW OR=0.999, 95% CI = 0.989-1.008, P=0.800). All sensitivity analyses revealed consistent results. Conclusions: There was no significant change in serum DKK-1 concentration between AS patients and healthy controls. In addition, no causal relationship exists between serum DKK-1 levels and AS risk.

No genetic causal association between systemic lupus erythematosus and COVID-19.

Objective: Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. Methods: In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. Results: The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found. Conclusion: The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.

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.

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.

Causal effect of polyunsaturated fatty acids on bone mineral density and fracture.

Background: Polyunsaturated fatty acids (PUFAs) are closely related to osteoporosis. To test their causal relationship, we conducted a Mendelian randomization (MR) analysis. Methods: We analyzed the causal relationship between four PUFAs measures, n-3 PUFAs (n-3), n-6 PUFAs (n-6), the ratio of n-3 PUFAs to total fatty acids (n-3 pct), and the ratio of n-6 PUFAs to n-3 PUFAs (n-6 to n-3), and five measures of osteoporosis, including estimated bone mineral density (eBMD), forearm (FA) BMD, femoral neck (FN) BMD, lumbar spine (LS) BMD, and fracture, using two-sample MR analysis. In order to verify the direct effect between PUFAs and BMD, we chose interleukin-6 (IL-6), tumor necrosis factor-ß (TNF-ß), and bone morphogenetic proteins 7 (BMP-7), three markers or cytokines strongly related to BMD, as possible confounding factors, and analyzed the possible causal relationships between them and PUFAs or BMD by MR. Inverse variance weighting (IVW), MR-Egger, weighted and weighted median were conducted. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods were used to evaluate the potential pleiotropy of instrumental variables (IVs) and outliers were identified by MR-PRESSO. Cochran's Q statistic was used to detect the heterogeneity among IVs. Leave-one-out sensitivity analysis was used to find SNPs that have a significant impact on the results. All results were corrected by the Bonferroni correction. Results: The IVW results showed that n-3 PUFAs (OR = 1.030, 95% CI: 1.013, 1.047, P = 0.001) and n-6 PUFAs (OR = 1.053, 95% CI: 1.034, 1.072, P < 0.001) were positively correlated with eBMD, while n-6 to n-3 (OR = 0.947, 95% CI: 0.924, 0.970, P < 0.001) were negatively correlated with eBMD. These casual relationships still existed after Bonferroni correction. There were positive effects of n-3 PUFAs on FA BMD (OR = 1.090, 95% CI: 1.011, 1.176, P = 0.025) and LS BMD (OR = 1.056, 95% CI: 1.011, 1.104, P = 0.014), n-3 pct on eBMD (OR = 1.028, 95% CI: 1.002, 1.055, P = 0.035) and FA BMD (OR = 1.090, 95% CI: 1.011, 1.174, P = 0.025), n-6 to n-3 on LS BMD (OR = 1.071, 95% CI: 1.021, 1.124, P = 0.005); negative effects of n-3 pct on fracture (OR = 0.953, 95% CI: 0.918, 0.988, P = 0.009) and n-6 to n-3 on FA BMD (OR = 0.910, 95% CI: 0.837, 0.988, P = 0.025). However, these causal effects all disappeared after Bonferroni correction (all P > 0.0025). None of IL-6, TNF-ß, and BMP-7 had a causal effect on PUFA and BMD simultaneously (all P > 0.05). Conclusion: Evidence from this MR study supports the genetically predicted causal effects of n-3, n-6, n-3 pct, and n-6 to n-3 on eBMD. In addition, n-3 not only associate with FA BMD and LS BMD through its own level and n-6 to n-3, but also link to fracture through n-3 pct.