Effectiveness and safety of rivaroxaban for anticoagulation therapy in COVID-19: A meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.

Uncovering hub genes in sepsis through bioinformatics analysis.

In-depth studies on the mechanisms of pathogenesis of sepsis and diagnostic biomarkers in the early stages may be the key to developing individualized and effective treatment strategies. This study aimed to identify sepsis-related hub genes and evaluate their diagnostic reliability. The gene expression profiles of GSE4607 and GSE131761 were obtained from the Gene Expression Omnibus. Differentially co-expressed genes between the sepsis and control groups were screened. Single-sample gene set enrichment analysis and gene set variation analysis were performed to investigate the biological functions of the hub genes. A receiver operating characteristic curve was used to evaluate diagnostic value. Datasets GSE154918 and GSE185263 were used as external validation datasets to verify the reliability of the hub genes. Four differentially co-expressed genes, FAM89A, FFAR3, G0S2, and FGF13, were extracted using a weighted gene co-expression network analysis and differential gene expression analysis methods. These 4 genes were upregulated in the sepsis group and were distinct from those in the controls. Moreover, the receiver operating characteristic curves of the 4 genes exhibited considerable diagnostic value in discriminating septic blood samples from those of the non-septic control group. The reliability and consistency of these 4 genes were externally validated. Single-sample gene set enrichment analysis and gene set variation analysis analyses indicated that the 4 hub genes were significantly correlated with the regulation of immunity and metabolism in sepsis. The identified FAM89A, FFAR3, G0S2, and FGF13 genes may help elucidate the molecular mechanisms underlying sepsis and drive the introduction of new biomarkers to advance diagnosis and treatment.

Intravenous high-dose vitamin C monotherapy for sepsis and septic shock: A meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness of intravenous high-dose vitamin C in sepsis and septic shock patients by meta-analysis. METHODS: The PubMed, Embase, and Cochrane Library electronic databases were searched to identify relevant studies. The primary outcome was defined as the short-term all-cause mortality rate. Secondary outcomes included duration of vasoactive drug use, intensive care unit length of stay, sequential organ failure assessment scores up to 96 hours after treatment and 90-day mortality. Review Manager version 5.4 was used to perform the meta-analysis. Relative risk and mean differences (MD) with 95% confidence intervals were determined using fixed- or random-effects models. RESULTS: Eight randomized controlled trials (RCTs) comprising 1394 patients were eligible for assessment. Overall, the pooled results showed that high-dose vitamin C decreased short-term all-cause mortality in patients with sepsis, but no significant differences were observed in patients with septic shock. Additionally, high-dose vitamin C was associated with decreased duration of vasoactive drug use in patients with sepsis, but not in patients with septic shock. However, it did not significantly affect the duration of intensive care unit stay in RCTs of patients with sepsis and septic shock. Additionally, it did not significantly affect sequential organ failure assessment scores 96 hours post-treatment or 90-day mortality. CONCLUSION: These results suggest that intravenous high-dose vitamin C may improve outcomes in patients with sepsis, but do not benefit patients with septic shock. Further RCTs and other studies should be conducted to determine whether vitamin C should be recommended as an adjunctive sepsis treatment.

Relationship between temperature variability and daily hospitalisations in Hong Kong over two decades.

Background: Studies have highlighted the impacts of temperature variability (TV) on mortality from respiratory diseases and cardiovascular diseases, with inconsistent results specifically in subtropical urban areas than temperate ones. We aimed to fully determine TV-associated health risks over a spectrum of diseases and various subgroups in a subtropical setting. Methods: Using inpatient data from all public hospitals in Hong Kong from 1999 to 2019, we examined the TV-hospitalisation associations by causes, ages, and seasons by fitting a quasi-Poisson regression. We presented the results as estimated percentage changes of hospitalisations per interquartile range (IQR) of TV. Results: TVs in exposure days from 0-5 days (TV0-5) to 0-7 days (TV0-7) had detrimental effects on hospitalisation risks in Hong Kong. The overall population was significantly affected over TV0-5 to TV0-7 in endocrine, nutritional and metabolic (from 0.53% to 0.58%), respiratory system (from 0.38% to 0.53%), and circulatory systems diseases (from 0.47% to 0.56%). While we found no association with seasonal disparities, we did observe notable disparities by age, highlighting older adults' vulnerability to TVs. For example, people aged ≥65 years experienced the highest change of 0.88% (95% CI = 0.34%, 1.41%) in hospitalizations for injury and poisoning per IQR increase in TV0-4. Conclusions: Our population-based study highlighted that TV-related health burden, usually regarded as minimal compared to other environmental factors, should receive more attention and be addressed in future relevant health policies, especially for vulnerable populations during the cold seasons.

Chronic exposure to ambient PM2.5/NO2 and respiratory health in school children: A prospective cohort study in Hong Kong.

Despite increasing concerns about the detrimental effects of air pollution on respiratory health, limited evidence is available on these effects in the Hong Kong population, especially in children. In this prospective cohort study between 2012 and 2017, we aimed to investigate the associations between exposure to air pollution (concentrations of fine particulate matter [PM2.5] and nitrogen dioxide [NO2]) and respiratory health (lung function parameters and respiratory diseases and symptoms) in schoolchildren. We recruited 5612 schoolchildren aged 6-16 years in Hong Kong. We estimated the annual average concentrations of ambient PM2.5 and NO2 at each participant's address using spatiotemporal models. We conducted spirometry tests on all participants to measure their lung function parameters and used a self-administered questionnaire to collect information on their respiratory diseases and symptoms and a wide range of covariates. Linear mixed models were used to investigate the associations between exposure to air pollution and lung function. Mixed-effects logistic regression models with random effects were used to investigate the associations of exposure to air pollution with respiratory diseases and symptoms. In all of the participants, every 5-µg/m3 increase in the ambient PM2.5 concentration was associated with changes of - 13.90 ml (95 % confidence interval [CI]: -23.65 ml, -4.10 ml), - 4.20 ml (-15.60 ml, 7.15 ml), 27.20 ml/s (-3.95 ml/s, 58.35 ml/s), and - 19.80 ml/s (-38.35 ml/s, -1.25 ml/s) in forced expiratory volume in 1 s, forced vital capacity, peak expiratory flow, and maximal mid-expiratory flow, respectively. The corresponding lung function estimates for every 5-µg/m3 increase in the ambient NO2 concentration were - 2.70 ml (-6.05 ml, 0.60 ml), - 1.40 ml (-5.40 ml, 2.60 ml), - 6.60 ml/s (-19.75 ml/s, 6.55 ml/s), and - 3.05 ml/s (-11.10 ml/s, 5.00 ml/s), respectively. We did not observe significant associations between PM2.5/NO2 exposure and most respiratory diseases and symptoms. Stratified analyses by sex and age showed that the associations between exposure to air pollution and lung function parameters were stronger in male participants and older participants (11-14 year old group) than in female participants and younger participants (6-10 year old group), respectively. Our results suggest that chronic exposure to air pollution is detrimental to the respiratory health of schoolchildren, especially that of older boys. Our findings reinforce the importance of air pollution mitigation to protect schoolchildren's respiratory health.

Effectiveness of corticosteroids to treat coronavirus disease 2019 symptoms: A meta-analysis.

Objective: Currently, corticosteroids are widely used to treat coronavirus disease 2019 (COVID-19) symptoms. However, the therapeutic role of corticosteroids remains highly controversial. To that end, we aimed to assess the efficacy of corticosteroids in treating COVID-19 patients. Method: We searched PubMed, Embase, and Cochrane Library to select suitable studies. Our primary study endpoint was all-cause mortality. The secondary study endpoint was the length of hospital stay. Results: A total of 9 randomized controlled trials (RCTs) with 7907 patients were assessed. The pooled result indicated that corticosteroids treatment could significantly reduce all-cause mortality in patients with COVID-19 (RR = 0.88, 95% CI [0.82, 0.95], P = 0.002). When subgroup analyses were performed, we found that corticosteroids were associated with decreased all-cause mortality in severe COVID-19 patients (RR = 0.77, 95% CI [0.68, 0.88], P < 0.0001), however no obvious difference was observed in all-cause mortality of non-severe COVID-19 patients between the corticosteroid and control group (RR = 0.96, 95% CI [0.86, 1.06], P = 0.41), meanwhile, a low dose (RR = 0.89, 95% CI [0.82, 0.97], P = 0.007) of dexamethasone (RR = 0.9, 95% CI [0.83, 0.98], P = 0.01) with a long treatment course (RR = 0.89, 95% CI [0.82, 0.98], P = 0.02) was beneficial for all-cause mortality in COVID-19 patients. Additionally, we found that corticosteroids might be associated with a longer length of hospital stay in non-severe COVID-19 patients (MD = 3.83, 95% CI [1.11, 6.56], P = 0.006). Conclusion: Our results showed that corticosteroid therapy was related to a reduction in all-cause mortality in severe COVID-19 patients. However, in patients with non-severe COVID-19, the use of corticosteroids did not decrease all-cause mortality and may prolong the duration of hospital stay. In addition, we revealed that a low dose of dexamethasone with a long treatment course could reduce all-cause mortality in COVID-19 patients.

Objetivo: Actualmente, los glucocorticoides se utilizan ampliamente para tratar los síntomas de la enfermedad por coronavirus 2019 (COVID-19). Sin embargo, el papel terapéutico de los glucocorticoides sigue siendo muy controvertido, por ello, nos propusimos evaluar su eficacia en el tratamiento de los pacientes con COVID-19. Método: Se realizaron búsquedas en PubMed, Embase y Cochrane Library para seleccionar los estudios adecuados. El criterio de valoración principal del estudio fue la mortalidad por todas las causas. El criterio de valoración secundario del estudio fue la duración de la estancia en el hospital. Resultados: Se evaluó un total de 9 ensayos controlados aleatorizados con 7.907 pacientes. En general, el tratamiento con glucocorticoides redujo la mortalidad por todas las causas en los pacientes con COVID-19 (RR = 0,88, IC 95% [0,82; 0,95], p = 0,002). Al realizar análisis de subgrupos, se observó que los glucocorticoides se asociaban a una disminución de la mortalidad por todas las causas en los pacientes con COVID-19 grave (RR = 0,77, IC 95% [0,68; 0,88], p < 0,0001), sin embargo no se observaron diferencias evidentes en la mortalidad por todas las causas de los pacientes con COVID-19 no grave entre el grupo de glucocorticoides y el de control (RR = 0,96, IC 95% [0,86; 1,06], p = 0,41), mientras que una dosis baja (RR = 0,89, IC 95% [0,82; 0,97], p = 0,007) de dexametasona (RR = 0,9, IC 95% [0,83; 0,98], p = 0,01) con un curso de tratamiento largo (RR = 0,89, IC 95% [0,82; 0,98], p = 0,02) fue beneficiosa para la mortalidad por todas las causas en los pacientes con COVID-19. Además, encontramos que los glucocorticoides podrían estar asociados con una mayor duración de la estancia hospitalaria en los pacientes con COVID-19 no grave (DM = 3,83, IC 95% [1,11; 6,56], p = 0,006). Conclusión: Nuestros resultados mostraron que el tratamiento con glucocorticoides estaba relacionado con una reducción de la mortalidad por todas las causas en los pacientes con COVID-19 grave. Sin embargo, en los pacientes con COVID-19 no grave, el uso de glucocorticoides no disminuyó la mortalidad por todas las causas y puede prolongar la duración de la estancia hospitalaria. Además, descubrimos que una dosis baja de dexametasona con un curso de tratamiento largo podría reducir la mortalidad por todas las causas en los pacientes con COVID-19.

Bioinformatics analysis of the circRNA-miRNA-mRNA network for atrial fibrillation.

Atrial fibrillation (AF) is a chronic and progressive disease, with advancing age, the morbidity of which will increase exponentially. Circular ribonucleic acids (RNAs; circRNAs) have gained a growing attention in the development of AF in recent years. The purpose of this study is to explore the mechanism of circRNA regulation in AF, in particular, the intricate interactions among circRNA, microRNA (miRNA), and messenger RNA (mRNA). Three datasets (GSE129409, GSE68475, and GSE79768) were obtained from the Gene Expression Omnibus database to screen differentially expressed (DE) circRNAs, DE miRNAs, and DE mRNAs in AF, respectively. Based on circRNA-miRNA pairs and miRNA-mRNA pairs, a competing endogenous RNAs (ceRNAs) network was built. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of DE mRNAs in the network were performed and protein-protein interaction (PPI) networks were established to identify hub genes. Finally, a circRNA-miRNA-hub gene subnetwork was constructed. A total of 103 DE circRNAs, 16 DE miRNAs, and 110 DE mRNAs were screened in AF. Next, ceRNAs network in AF was constructed with 3 upregulated circRNAs, 2 downregulated circRNAs, 2 upregulated miRNAs, 2 downregulated miRNAs, 17 upregulated mRNAs, and 24 downregulated mRNAs. Thirty GO terms and 6 KEGG pathways were obtained. Besides, 6 hub genes (C-X-C chemokine receptor type 4 [CXCR4], C-X-C chemokine receptor type 2 [CXCR2], C-X-C motif chemokine 11 [CXCL11], neuromedin-U, B1 bradykinin receptor, and complement C3) were screened from constructing a PPI network. Finally, a circRNA-miRNA-hub gene subnetwork with 10 regulatory axes was constructed to describe the interactions among the differential circRNAs, miRNA, and hub genes. We speculated that hsa_circRNA_0056281/hsa_circRNA_0006665 -hsa-miR-613-CXCR4/CXCR2/CXCL11 regulatory axes and hsa_circRNA_0003638-hsa-miR-1207-3p-CXCR4 regulatory axis may be associated with the pathogenesis of AF.

Multi-pollutant air pollution and renal health in Asian children and adolescents: An 18-year longitudinal study.

BACKGROUND: Few studies have examined the effects of multi-pollutant air pollution on renal health, especially in children and adolescents. This study investigated the association between long-term ambient air pollution exposure and renal health in Asian children and adolescents. METHODS: This study included 10,942 children and adolescents from Taiwan and Hong Kong between 2000 and 2017. PM2.5, NO2 and O3 concentrations were estimated using satellite-based spatiotemporal regression models. Two-year average concentrations, those of the year of visit and the preceding year, were used. Linear mixed models were used to examine the association between air pollution and yearly changes in estimated glomerular filtration rate (eGFR). Cox regression models with time-dependent covariates were used to examine the association between air pollution and the development of chronic kidney disease (CKD). RESULTS: Median age of the participants was 19 years (range: 2-25). The overall average concentration of PM2.5, NO2 and O3 was 26.7 µg/m3, 44.1 µg/m3 and 51.1 µg/m3, respectively. The mean yearly change in eGFR was 0.37 µL/min/1.73 m2 and the incidence rate of CKD was 6.8 per 1,000 person-years. In single-pollutant models, each 10 µg/m3 increase in PM2.5 was associated with a 0.45 µL/min/1.73 m2 [95% confidence interval (CI): 0.28-0.63] reduction in the yearly increase in eGFR and 53% [hazard ratio (HR): 1.53 (95%CI: 1.07-2.2)] greater risk of incident CKD. Each 10 µg/m3 increase in NO2 was associated with a 7% [HR (95%CI): 1.07 (1.00-1.15)] higher risk of incident CKD, while an equivalent increase in O3 was associated with a 19% [HR (95%CI): 0.81 (0.67-0.98)] lower risk. CONCLUSIONS: Long-term exposure to ambient PM2.5 and NO2 was associated with a slower growth of eGFR and a higher risk of incident CKD in children and adolescents. Our findings suggest that air pollution control in early life is imperative to improve lifelong renal health and alleviate the CKD burden.

Effectiveness of corticosteroids to treat coronavirus disease 2019 symptoms: A meta-analysis.

OBJECTIVE: Currently, corticosteroids are widely used to treat coronavirus disease 2019 (COVID-19) symptoms. However, the therapeutic role of corticosteroids remains highly controversial. To that end, we aimed to assess the efficacy of corticosteroids in treating COVID-19 patients. METHOD: We searched PubMed, Embase, and Cochrane Library to select suitable studies. Our primary study endpoint was all-cause mortality. The secondary study endpoint was the length of hospital stay. RESULTS: A total of 9 randomized controlled trials (RCTs) with 7907 patients were assessed. The pooled result indicated that corticosteroids treatment could significantly reduce all-cause mortality in patients with COVID-19 (RR=0.88, 95% CI [0.82, 0.95], P=0.002). When subgroup analyses were performed, we found that corticosteroids were associated with decreased all-cause mortality in severe COVID-19 patients (RR=0.77, 95% CI [0.68, 0.88], P<0.0001), however no obvious difference was observed in all-cause mortality of non-severe COVID-19 patients between the corticosteroid and control group (RR=0.96, 95% CI [0.86, 1.06], P=0.41), meanwhile, a low dose (RR=0.89, 95% CI [0.82, 0.97], P=0.007) of dexamethasone (RR=0.9, 95% CI [0.83, 0.98], P=0.01) with a long treatment course (RR=0.89, 95% CI [0.82, 0.98], P=0.02) was beneficial for all-cause mortality in COVID-19 patients. Additionally, we found that corticosteroids might be associated with a longer length of hospital stay in non-severe COVID-19 patients (MD=3.83, 95% CI [1.11, 6.56], P=0.006). CONCLUSION: Our results showed that corticosteroid therapy was related to a reduction in all-cause mortality in severe COVID-19 patients. However, in patients with non-severe COVID-19, the use of corticosteroids did not decrease all-cause mortality and may prolong the duration of hospital stay. In addition, we revealed that a low dose of dexamethasone with a long treatment course could reduce all-cause mortality in COVID-19 patients.

Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis.

BACKGROUND: The use of vasopressors is vital in septic shock. However, the optimal timing of treatment remains unclear. Therefore, we aimed to explore the impact of early norepinephrine initiation on the survival of patients with septic shock. METHODS: We selected 4253 patients from the Medical Information Mart for Intensive Care IV database between 2008 and 2019. The primary outcome was 28-day mortality. Propensity score matching (PSM) was applied to minimize between-group imbalances, and a restricted mean survival time was used to quantify the beneficial impact of early norepinephrine treatment on survival. Sensitivity analyses were conducted to test the robustness of the study results in multiple cohorts. RESULTS: In the PSM cohort, 2862 patients were equally assigned to early (receiving norepinephrine within the first 3 h) and delayed (> 3 h) norepinephrine initiation groups. Patients in the early norepinephrine initiation group received significantly less fluid therapy (0 vs. 79 mL/kg), had lower 28-day mortality (30.0% vs. 37.8%), longer survival days (21.89 vs. 20.37 days), shorter duration of intensive care unit (4.9 vs. 7.2 days) and hospital stays (12.4 vs. 13.6 days), shorter duration of supportive norepinephrine and invasive mechanical ventilation, lower incidence of organ failure progression (64.4% vs. 79.2%) within 24 h after shock onset, and higher mean arterial pressure within 6 and 24 h after shock onset than patients in the delayed norepinephrine initiation group (p < 0.05). CONCLUSIONS: Norepinephrine initiation within the first 3 h, regardless of preload dependency, was associated with longer survival time and shorter duration of supportive norepinephrine and invasive mechanical ventilation and may delay or partially reverse rapid onset organ failure.

Combined effects of chronic PM2.5 exposure and habitual exercise on cancer mortality: a longitudinal cohort study.

BACKGROUND: Exercise may increase the inhalation and deposition of air pollutants, which may counteract its beneficial effects. We thus examined the combined effects of chronic exposure to fine particulate matter (PM2.5) and habitual exercise on the risk of death from cancer in Taiwan. PATIENTS AND METHODS: A total of 384 128 adults (≥18 years of age) were recruited for a medical screening programme between 2001 and 2016, yielding 842 384 medical-examination records. All participants were followed up until 31 May 2019. Vital data were obtained from the National Death Registry of Taiwan and the ambient PM2.5 exposure was estimated using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. The time-dependent Cox-regression model was used to evaluate the combined effects. RESULTS: A greater amount of habitual exercise was associated with lower risk of death from cancer, whilst a higher level of PM2.5 exposure was associated with a higher risk of death from cancer. The inverse associations of habitual exercise with death from cancer were not modified by chronic exposure to PM2.5. The participants in the group with a high level of exercise and a low level of PM2.5 exposure exhibited a 35% lower risk of death from cancer than those in the group with a low level of exercise and a high level of PM2.5 exposure (95% confidence interval: 28%, 42%). CONCLUSIONS: Increased levels of exercise and reduced exposure levels of PM2.5 are associated with a lower risk of death from cancer. Habitual exercise reduces the risk of death from cancer regardless of the levels of chronic PM2.5 exposure. Our results indicate that habitual exercise is a suitable health-promotion strategy even for people who reside in moderately polluted regions.

Efficacy and safety of dexmedetomidine in sepsis patients requiring mechanical ventilation: a systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Currently, dexmedetomidine is widely used in the treatment of sepsis patients requiring mechanical ventilation; however, its role remains controversial. The aim of this study was to assess the efficacy and safety of dexmedetomidine in sepsis patients requiring mechanical ventilation. METHODS: The PubMed, Embase and Cochrane Library electronic databases were searched to identify relevant studies; Review Manager version 5.4 was used to perform the meta-analysis. Primary outcomes included the all-cause mortality rate at the longest follow-up available and the duration of mechanical ventilation. Secondary outcomes included length of intensive care unit (ICU) stay, length of hospital stay, and adverse events (bradycardia). RESULTS: Five randomized controlled trials (RCTs), including 926 patients, were assessed. Overall, dexmedetomidine did not reduce all-cause mortality in mechanically ventilated patients with sepsis (relative risk [RR]: 0.9, 95% confidence interval [CI]: 0.77 to 1.05, p = 0.18, I2 = 37%). However, dexmedetomidine was associated with decreases in the length of hospital stay (mean difference [MD]: -2.99, 95% CI: -4.72 to -1.26, p = 0.0007, I2 = 0%), ICU length of stay (MD: -1.15, 95% CI: -2.06 to -0.24, p = 0.01, I2 = 32%) and duration of mechanical ventilation (MD: -0.72, 95% CI: -1.38 to -0.07, p = 0.03, I2 = 20%). However, dexmedetomidine increased the risk for bradycardia (22% versus 12.6%, respectively; RR: 1.73, 95% CI: 1.24 to 2.41, p = 0.001, I2  = 0%). WHAT IS NEW AND CONCLUSION: Results suggested that dexmedetomidine did not reduce all-cause mortality in mechanically ventilated patients with sepsis. However, it was associated with decreases in length of hospital stay, ICU length of stay and duration of mechanical ventilation, although it increased the risk for bradycardia.

The Construction and Comprehensive Analysis of a ceRNA Immunoregulatory Network and Tissue-Infiltrating Immune Cells in Atrial Fibrillation.

BACKGROUND: At present, the mechanisms behind atrial fibrillation (AF) pathogenesis are still unclear. We construct a ceRNA immunoregulatory network to further understand the mechanism of AF. METHODS: Four AF mRNA datasets from the Gene Expression Omnibus (GEO) database were integrated by SVA method. AF-related immune genes (AF-IRGs) were selected via combining ImmPort database with the genes in the module most associated with AF obtained by a weighted gene coexpression network analysis (WGCNA). Then, circRNA and miRNA expressions from the GEO database were extracted and mapped with related databases. Next, an immune-related circRNA-miRNA-mRNA ceRNA network was constructed and hub genes were filtered from a protein-protein interaction (PPI) network, and the differentially expressed (DE) hub genes in AF were further screened. Additionally, immune infiltration was investigated in AF by using CIBERSORT. Subsequently, the relationships between DE hub genes and AF-related infiltrating immune cells were performed by using Pearson correlation coefficients. Ulteriorly, the immune-cells-related ceRNA subnetwork in AF was built. RESULTS: A total of 95 AF-IRGs were detected, and an immune-related ceRNA network in AF was constructed with 12 circRNAs, 7 miRNAs and 50 mRNAs. The immune infiltration analysis indicated that a higher level of neutrophils, as well as a lower level of T cells regulatory (Tregs) and NK cells activated in AF. Four DE hub genes (CXCL12, IL7R, TNFSF13B, CD8A) were associated with Tregs or NK cells activated immune cells (P < 0.05). Tregs or NK cells activated immune cells-related ceRNA subnetwork including 5 circRNAs (has_circ_0001190, has_circ_0006725, has_circ_0079284, has_circ_0005299, and has_circ_0002103), 4 miRNAs (has-miR-198, has-miR-623, has-miR-1246, and has-miR-339-3p) and 4 DE hub genes was eventually constructed in AF. CONCLUSION: Our results provide new insights into the molecular mechanisms governing AF progression from the perspective of immune-related ceRNA network.

Effects of air pollution and habitual exercise on the risk of death: a longitudinal cohort study.

BACKGROUND: Exercise may exacerbate the adverse health effects of air pollution by increasing the inhalation of air pollutants. We investigated the combined effects of long-term exposure to fine particle matter (PM2.5) and habitual exercise on deaths from natural causes in Taiwan. METHODS: We recruited 384 130 adults (aged ≥ 18 yr) with 842 394 medical examination records between 2001 and 2016, and followed all participants until May 31, 2019. We obtained vital data from the National Death Registry of Taiwan. We estimated PM2.5 exposure using a satellite-based spatiotemporal model, and collected information on exercise habits using a standard self-administered questionnaire. We analyzed the data using a Cox regression model with time-dependent covariates. RESULTS: A higher level of habitual exercise was associated with a lower risk of death from natural causes, compared with inactivity (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.80-0.88 for the moderate exercise group; HR 0.65, 95% CI 0.62-0.68 for the high exercise groups), whereas a higher PM2.5 exposure was associated with a higher risk of death from natural causes compared with lower exposure (HR 1.02, 95% CI 0.98-1.07, and HR 1.15, 95% CI 1.10-1.20, for the moderate and high PM2.5 exposure groups, respectively). Compared with inactive adults with high PM2.5 exposure, adults with high levels of habitual exercise and low PM2.5 exposure had a substantially lower risk of death from natural causes. We found a minor, but statistically significant, interaction effect between exercise and PM2.5 exposure on risk of death (HR 1.03 95% CI 1.01-1.06). Subgroup analyses, stratified by PM2.5 categories, suggested that moderate and high levels of exercise were associated with a lower risk of death in each PM2.5 stratum, compared with inactivity. INTERPRETATION: Increased levels of exercise and reduced PM2.5 exposure are associated with a lower risk of death from natural causes. Habitual exercise can reduce risk regardless of the levels of PM2.5 exposure. Our results suggest that exercise is a safe health improvement strategy, even for people residing in relatively polluted regions.

Combined effects of chronic PM2.5 exposure and habitual exercise on renal function and chronic kidney disease: A longitudinal cohort study.

BACKGROUND: We investigated the combined effects of chronic PM2.5 exposure and habitual exercise on the decline of renal function and the incidence of chronic kidney disease (CKD) in a large cohort in Taiwan. METHODS: The present data analysis included a total of 108,615 participants aged 18 years or above who were recruited between 2001 and 2016. All participants underwent at least two medical examinations. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The incident of eGFR decline ≥30% was defined as a decline in eGFR of ≥30% during the study period, while the incident CKD was defined as an eGFR <60 mL/min/1.73 m2 or a newly self-reported physician-diagnosed CKD in the subsequent visits. The satellite-based spatiotemporal model was used to estimate PM2.5 exposure at each participant's address. Information on habitual exercise was collected using a standard self-administered questionnaire. The Cox regression model with time-dependent covariates was used for data analyses. RESULTS: Higher habitual exercise was associated with lower risks of renal function decline and CKD development, whereas higher PM2.5 exposure was associated with higher risks of renal function decline and CKD development. We found no significant interaction effect between PM2.5 and habitual exercise, with an HR (95% CI) of 1.02 (0.97, 1.07) for incident eGFR decline ≥30% and 1.00 (0.95, 1.05) for CKD development. Compared to participants with inactive-exercise and high-PM2.5, participants with high-exercise and low-PM2.5 had 74% and 61% lower risks of renal function decline and CKD development, respectively. CONCLUSION: Increased habitual exercise and reduced PM2.5 exposures are associated with lower risks of renal function decline and CKD development. Habitual exercise reduces risks of renal function decline and CKD development regardless of the levels of chronic PM2.5 exposure. Our study suggests that habitual exercise is a safe approach for kidney health improvement even for people residing in relatively polluted areas and should be promoted.

Physical distancing implementation, ambient temperature and Covid-19 containment: An observational study in the United States.

Governments may relax physical distancing interventions for coronavirus disease 2019 (Covid-19) containment in warm seasons/areas to prevent economic contractions. However, it is not clear whether higher temperature may offset the transmission risk posed by this relaxation. This study aims to investigate the associations of the effective reproductive number (Rt) of Covid-19 with ambient temperature and the implementation of physical distancing interventions in the United States (US). This study included 50 states and one territory of the US with 4,532,650 confirmed cases between 29 January and 31 July 2020. We used an interrupted time-series model with a state-level random intercept for data analysis. An interaction term of 'physical distancing×temperature' was included to examine their interactions. Stratified analyses by temperature and physical distancing implementation were also performed to analyse the modifying effects. The overall median (interquartile range) Rt was 1.2 (1.0-2.3). The implementation of physical distancing was associated with a 12% decrease in the risk of Rt (relative risk [RR]: 0.88, 95% confident interval [CI]: 0.86-0.89), and each 5 °C increase in temperature was associated with a 2% decrease (RR: 0.98, 95%CI: 0.97-0.98). We observed a statistically significant interaction between temperature and physical distancing implementation, but all the RRs were small (close to one). The containing effects of high temperature were attenuated by 5.1% when physical distancing was implemented. The association of COVID-19 Rt with physical distancing implementation was more stable (0.88 vs. 0.89 in days when temperature was low and high, respectively). Increased temperature did not offset the risk of Covid-19 Rt posed by the relaxation of physical distancing implementation. Our study does not recommend relaxing the implementation of physical distancing interventions in warm seasons/areas.

Reduced Ambient PM2.5 Was Associated with a Decreased Risk of Chronic Kidney Disease: A Longitudinal Cohort Study.

Many countries have dedicated to the mitigation of air pollution in the past several decades. However, evidence of beneficial effects of air quality improvement on chronic kidney disease (CKD) remains limited. We thus investigated the effects of dynamic changes (including deterioration and improvement) in air quality on the incidence of CKD in a longitudinal study in Taiwan. During 2001-2016, this study recruited a total of 163,197 Taiwanese residents who received at least two standard physical examinations. The level of fine particle matter (PM2.5) was estimated using a high-resolution (1 km2) satellite-based spatio-temporal model. We defined changes of PM2.5 concentrations (ΔPM2.5) as the difference between the two-year average measurements during follow-up and during the immediately preceding visit. The time-dependent Cox regression model was adopted to evaluate the relationships between ΔPM2.5 and the incidence of CKD after adjusting for a series of covariates. The concentrations of PM2.5 in Taiwan peaked around 2004 and began to decrease since 2005. We observed an approximate linear concentration-response relationship of ΔPM2.5 with CKD incidence. Every 5 µg/m3 decrease in the ambient concentration of PM2.5 was associated with a 25% reduced risk of CKD development [hazard ratio (HR): 0.75; 95% CI: 0.73, 0.78]. In conclusion, this study demonstrated that the improvement of PM2.5 air quality might be associated with a lower risk of CKD development. Our findings indicate that reducing air pollution may effectively prevent the development of CKD.

Increase of donor derived tumor occurrence by transfer of ex vivo expanded antigen specific regulatory T cells.

OBJECTIVES: Using regulatory T cells (Tregs) as a cellular therapy to control rejection is an attractive immunosuppressive strategy in transplantation, but immunosuppression mediated by Tregs need to be investigated before application. METHODS: In our experiment, mature Dendritic Cells (DCs) were generated through inducing bone marrow cells of C57BL/6 (H-2b) mice. CD4+CD25+Tregs were sorted by magnetic activated cell sorting (MACS) from BALB/C (H-2d) mice, and Tregs were expanded ex vivo with anti-CD3/CD28 microbeads and high concentration of recombinant murine (rm) IL-2 for 14 days, after that, expanded polyclonal Tregs were collected and cocultured with mature DCs (H-2b) in the presence of lower concentration of rmIL-2 for 7 days to get antigen-specific Tregs. Subsequently, BALB/C mice were randomly divided into three groups: BALB/c mice were inoculated with 5 × 105 B16-F10 (H-2b) cells via tail vein, the other were inoculated with 1 × 107 BALB/c expanded polyclonal Tregs and 5 × 105 B16-F10, the last with 1 × 107 antigen-specific BALB/c Tregs and 5 × 105 B16-F10 cells. After 14 days, mice were sacrificed and the black tumor nodules in lungs were counted. RESULTS: Adoptive transfer of ex vivo expanded polyclonal Tregs rendered BALB/c mice (recipient) susceptible to MHC-mismatched tumor (B16-F10 cells, H-2b). If ex vivo expanded polyclonal Tregs from BALB/c were cocultured with mature DCs from C57BL/6 after expansion, suppression of tumor immunity against B16-F10 cells was further. CONCLUSION: We suggested that ex vivo expanded antigen-specific Tregs could more dampen recipient tumor immunity compare with polyclonal Tregs, and the increased risk of donor derived tumor should be considered.

Habitual exercise is associated with reduced risk of diabetes regardless of air pollution: a longitudinal cohort study.

AIMS/HYPOTHESIS: Physical activity may increase a person's inhalation of air pollutants and exacerbate the adverse health effects. This study aimed to investigate the combined associations of chronic exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and habitual physical activity with the incidence of type 2 diabetes in Taiwan. METHODS: We selected 156,314 non-diabetic adults (≥18 years old) who joined an ongoing longitudinal cohort between 2001 and 2016. Incident type 2 diabetes was identified at the follow-up medical examinations. Two-year mean PM2.5 exposure was estimated at each participant's address using a satellite-based spatiotemporal model. Information on physical activity and a wide range of covariates was collected using a standard self-administered questionnaire. We analysed the data using a Cox regression model with time-varying covariates. An interaction term between PM2.5 and physical activity was included to examine the overall interaction effects. RESULTS: Compared with high physical activity, moderate and inactive/low physical activity were associated with a higher risk of diabetes (HR [95% CI] 1.31 [1.22, 1.41] and 1.56 [1.46, 1.68], respectively). Participants with moderate/high PM2.5 had a higher risk of type 2 diabetes than the participants exposed to low PM2.5 (HR 1.31 [1.22, 1.40] and 1.94 [1.76, 2.14], respectively). The participants with high physical activity and low PM2.5 had a 64% lower risk of type 2 diabetes than those with inactive/low physical activity and high PM2.5. CONCLUSIONS/INTERPRETATION: Higher physical activity and lower PM2.5 exposure are associated with lower risk of type 2 diabetes. Habitual physical activity can reduce the risk of diabetes regardless of the levels of PM2.5 exposure. Our results indicate that habitual physical activity is a safe diabetes prevention strategy for people residing in relatively polluted regions.

Effectiveness of non-pharmaceutical interventions on COVID-19 transmission in 190 countries from 23 January to 13 April 2020.

BACKGROUND: To evaluate and compare the effectiveness of four types of non-pharmaceutical interventions (NPIs) to contain the time-varying effective reproduction number (Rt) of coronavirus disease-2019 (COVID-19). METHODS: This study included 1,908,197 confirmed COVID-19 cases from 190 countries between 23 January and 13 April 2020. The implemented NPIs were categorised into four types: mandatory face mask in public, isolation or quarantine, social distancing and traffic restriction (referred to as mandatory mask, quarantine, distancing and traffic hereafter, respectively). RESULTS: The implementations of mandatory mask, quarantine, distancing and traffic were associated with changes (95% confidence interval, CI) of -15.14% (from -21.79% to -7.93%), -11.40% (from -13.66% to -9.07%), -42.94% (from -44.24% to -41.60%) and -9.26% (from -11.46% to -7.01%) in the Rt of COVID-19 when compared with those without the implementation of the corresponding measures. Distancing and the simultaneous implementation of two or more types of NPIs seemed to be associated with a greater decrease in the Rt of COVID-19. CONCLUSION: Our study indicates that NPIs can significantly contain the COVID-19 pandemic. Distancing and the simultaneous implementation of two or more NPIs should be the strategic priorities for containing COVID-19.