The joint effect of long-term exposure to multiple air pollutants on non-accidental and cause-specific mortality: A longitudinal cohort study.

The long-term joint impacts of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) on mortality are inconclusive. To bridge this research gap, we included 283,568 adults from the Taiwan MJ cohort between 2005 and 2016 and linked with the mortality data until 31 May 2019. Participants' annual average exposures to PM2.5, NO2, and O3 were estimated using satellite-based spatial-temporal models. We applied elastic net-regularised Cox models to construct a weighted environmental risk score (WERS) for the joint effects of three pollutants on non-accidental, cardiovascular, and cancer mortality and evaluated the contribution of each pollutant. The three pollutants jointly raised non-accidental mortality risk with a WERS hazard ratio (HR) of 1.186 (95% CI: 1.118-1.259) per standard deviation increase in each pollutant and weights of 72.8%, 15.2%, and 12.0% for PM2.5, NO2, and O3, respectively. The WERS increased cardiovascular death risk [HR: 1.248 (1.042-1.496)], with PM2.5 as the first contributor and O3 as the second. The WERS also elevated the cancer death risk [HR: 1.173 (1.083-1.270)], where PM2.5 played the dominant role and NO2 ranked second. Coordinated control of these three pollutants can optimise the health benefits of air quality improvements.

Comprehensive Analysis of the Expression, Prognostic Value, and Immune Infiltration Activities of GABRD in Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the tumors with the highest mortality rates. It is of the utmost significance to make an accurate prognostic assessment and to tailor one's treatment to the specific needs of the patient. Multiple lines of evidence point to the possibility that genetic variables and clinicopathological traits are connected to the onset and development of cancer. In the past, a number of studies have revealed that gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the advancement of a number of different cancers. However, its function in COAD was rarely reported. In this study, we analyzed TCGA datasets and identified 29 survival-related differentially expressed genes (DEGs) in COAD patients. In particular, GABRD expression was noticeably elevated in COAD specimens. There was a correlation between high GABRD expression and an advanced clinical stage. According to the results of the survival tests, patients whose GABRD expression was high had a lower overall survival time and progression-free survival time than those whose GABRD expression was low. GABRD expression was found to be an independent predictive predictor for overall survival, as determined by multivariate COX regression analysis. Additionally, the predictive nomogram model can accurately predict the fate of individuals with COAD. In addition, we observed that GABRD expressions were positively associated with the expression of T cells regulatory (Tregs), macrophages M0, while negatively associated with the expression of T cells CD8, T cells follicular helper, macrophages M1, dendritic cells activated, eosinophils, and T cells CD4 memory activated. The IC50 of BI-2536, bleomycin, embelin, FR-180204, GW843682X, LY317615, NSC-207895, rTRAIL, and VX-11e was higher in the GABRD high-expression group. In conclusion, we have shown evidence that GABRD is a novel biomarker that is connected with immune cell infiltration in COAD and may be utilized to predict the prognosis of COAD patients.

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.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); the total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3, 2021 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); The total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

Relationships among green space, ambient fine particulate matter, and cancer incidence in Taiwan: A 16-year retrospective cohort study.

INTRODUCTION: Green space and air pollution have been recognized as vital health determinants. There is a paucity of studies examining the interplay between green space, fine particulate matter (PM2.5), and the incidence of specific cancers. OBJECTIVE: We aimed to explore the contributions of green space and ambient PM2.5 to the risk of specific cancers in terms of the most common cancers based on incidence or mortality rate in Taiwan and to ascertain the interaction between green space and PM2.5 and their role in cancer risk. MATERIALS AND METHODS: This retrospective longitudinal cohort study included 407,415 participants. Data were obtained from the 2000-2015 Mei Jau Health Examination Database linked to the Taiwan Cancer Registry and Causes of Death datasets. All participants were aged ≥20 years and had no history of cancer. The environmental exposure were the normalized difference vegetation index (NDVI) and the 2-year average PM2.5 at baseline. Multivariate adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. We adjusted for covariates including demographics, anthropometrics, comorbidities, health behaviors, biochemical data, and environmental factors. RESULTS: During a median follow-up of 10.37 years, 11,576 cancer cases were reported. PM2.5 exposure increased the risk of all cancers (HR: 1.11, [95% CI: 1.06-1.15]), stomach cancer (HR: 1.27, [1.02-1.58]), endocrine gland cancer (HR: 2.13, [1.39-3.26]), breast cancer (HR: 1.12, [1.03-1.22]), and lung cancer (HR: 1.12, [1.01-1.24]). An increase in NDVI reduced the risk of prostate cancer (HR: 0.93, [0.88-0.99]) and lung cancer (HR: 0.95, [0.91-0.99]). NDVI influenced the incidence of prostate and all cancers by reducing PM2.5 concentrations. CONCLUSION: Long-term PM2.5 exposure is associated with an increased risk of some types of cancers. In contrast, an increase in environmental green space exposure is associated with lowering of the risk of prostate and lung cancer.

Long-term Exposure to Fine Particulate Matter and Mortality A Longitudinal Cohort Study of 400,459 Adults.

BACKGROUND: Cohort studies on the association between long-term exposure to fine particulate matter (PM2.5) and mortality have been well established for America and Europe, but limited and inconsistent in Asia with much higher air pollution. This study aims to investigate the associations between ambient PM2.5 and all-cause and cause-specific mortality over a period of rising and then declining PM2.5. METHODS: We enrolled a total of 400,459 adults from an open cohort between 2001 and 2016, and followed them up until 31 May 2019. We obtained mortality data from the National Death Registry maintained by the Ministry of Health and Welfare in Taiwan. We estimated ambient PM2.5 exposures using a satellite-based spatiotemporal model. We performed a Cox regression model with time-dependent covariates to investigate the associations of PM2.5 with deaths from all causes and specific causes. RESULTS: This study identified 14,627 deaths and had a total of 5 million person-years of follow-up. Each 10 µg/m3 increase in PM2.5 was associated with an increased hazard risk of 29% (95% confidence interval: 24%-35%) in all-cause mortality. Risk of death increased by 30% for natural causes, 20% for cancer, 42% for cardiovascular disease (CVD) causes, and 53% for influenza and pneumonia causes, for each 10 µg/m3 increase in PM2.5. Sensitivity analyses generally yielded similar results. CONCLUSION: Long-term exposure to ambient PM2.5 was associated with increased risks of all-cause mortality and deaths from cancers, natural causes, CVD, and influenza and pneumonia. Longitudinal study design should be encouraged for air pollution epidemiologic investigation.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

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.

Ambient Cumulative PM2.5 Exposure and the Risk of Lung Cancer Incidence and Mortality: A Retrospective Cohort Study.

Smoking, sex, air pollution, lifestyle, and diet may act independently or in concert with each other to contribute to the different outcomes of lung cancer (LC). This study aims to explore their associations with the carcinogenesis of LC, which will be useful for formulating further preventive strategies. This retrospective, longitudinal follow-up cohort study was carried out by connecting to the MJ Health Database, Taiwan Cancer Registry database, and Taiwan cause of death database from 2000 to 2015. The studied subjects were persons attending the health check-ups, distributed throughout the main island of Taiwan. Cox proportional hazards regression models were used to investigate the risk factors associated with LC development and mortality after stratifying by smoking status, with a special emphasis on ambient two-year average PM2.5 exposure, using a satellite-based spatiotemporal model at a resolution of 1 km2, and on dietary habit including consumption of fruits and vegetables. After a median follow-up of 12.3 years, 736 people developed LC, and 401 people died of LC-related causes. For never smokers, the risk of developing LC (aHR: 1.32, 95%CI: 1.12-1.56) and dying from LC-related causes (aHR: 1.28, 95%CI: 1.01-1.63) rises significantly with every 10 µg/m3 increment of PM2.5 exposure, but not for ever smokers. Daily consumption of more than two servings of vegetables and fruits is associated with lowering LC risk in ever smokers (aHR: 0.68, 95%CI: 0.47-0.97), and preventing PM2.5 exposure is associated with lowering LC risk for never smokers.

Interleukin-6 is a Strong Predictor of the Frequency of COPD Exacerbation Within 1 Year.

PURPOSE: Persistent chronic inflammation of chronic obstructive pulmonary disease (COPD) is associated with poor outcomes and frequently results in acute exacerbation. Predicting the number of exacerbations is important. Because interleukin 6 (IL-6) plays an important role in inducing and maintaining chronic inflammation, we sought to observe whether IL-6 measurement can predict the frequency of acute exacerbation of COPD. METHODS: We reviewed serum IL-6 concentrations of stable COPD patients from January 2016 to December 2017 and statistically analyzed them to determine the optimal threshold value to predict the frequency of COPD acute exacerbations. Outpatients with stable COPD were then recruited between January 2018 and December 2019 and grouped into a low IL-6 group and a high IL-6 group according to this threshold value. We then compared the number of exacerbations of COPD in 1 year between the two groups. RESULTS: We reviewed data from 95 COPD patients, who had a median of 1.00 exacerbations in preceding year; 35 of these patients had no fewer than two. The median IL-6 concentration was 8.80 pg/mL. IL-6 and hs-CRP were positively correlated with frequency of acute exacerbation in the preceding year, COPD assessment test (CAT) score and British medical research council (mMRC) score, and negatively correlated with forced expiratory volume in one second as percentage of predicted value (FEV1%pred) and FEV1/FVC% (forced vital capacity). IL-6 was the risk factor of COPD patients with two or more exacerbations in 1 year. Finally, we enrolled 65 COPD patients and divided into low IL-6 group and high IL-6 group; the high IL-6 group experienced more frequent exacerbations than did the low IL-6 group. CONCLUSION: An IL-6 measurement of 14.030 pg/mL or more is a risk factor for ≥2 acute exacerbations of COPD in the following year.

The Association Between Renal Function Decline and the Incidence of Urothelial Carcinoma: A 16-year Retrospective Cohort Study in Taiwan.

BACKGROUND: The incidence of cancer is higher among patients with end-stage renal disease but it remains uncertain whether a mild decrease in renal function affects cancer. OBJECTIVE: To measure the effect of impaired renal function, represented by the estimated glomerular filtration rate (eGFR), personal health behaviors, and long-term exposure to fine particulate matter (PM2.5) on the risk of urothelial carcinoma (UC) incidence. DESIGN SETTING AND PARTICIPANTS: We performed a population-based cohort study of 372 008 participants aged ≥30 yr with no prior cancer history using the MJ health examination database (2000-2015) and UC diagnosis data from the Taiwan Cancer Registry database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazards models were used to quantify the association between eGFR and UC incidence. RESULTS AND LIMITATIONS: We detected 383 UC cases during a median follow-up of 10.3 yr. Low eGFR was significantly associated with UC (p value for trend <0.01): compared to eGFR ≥90 ml/min/1.73 m2, the adjusted hazard ratio (HR) was 1.36 (95% confidence interval [CI] 0.98-1.88), 1.86 (95% CI 1.22-2.84), and 1.95 (95% CI 1.06-3.56) for eGFR strata of 60-89, 45-59, and <45 ml/min/1.73 m2, respectively. The risk remained elevated after stratifying the follow-up duration to check for reverse causality, and the dose-response relationship was stronger for women than for men. Current smoking (HR 1.34, 95% CI 1.02-1.77) and long-term exposure to PM2.5 concentrations ≥25.1 µg/m3 (HR 1.54, 95% CI 1.14-2.09) both significantly increased the risk of UC incidence. A significant dose-response relationship between PM2.5 and UC was also noted (p trend < 0.01). Limitations include the retrospective design and limited information on medical history. CONCLUSIONS: Lower renal function showed a dose-response relationship in elevating UC risk. Long-term exposure to PM2.5 is also a possible UC risk factor. PATIENT SUMMARY: People with kidney function that is lower than normal should monitor the health of their kidneys and other organs in the urinary system. Our study confirmed that as well as smoking, exposure to fine particulate matter in the air may be a risk factor for cancers of the urinary system.

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.

Reduced ambient PM2.5, better lung function, and decreased risk of chronic obstructive pulmonary disease.

BACKGROUND: Several studies reported that long-term exposure to fine particulate matter (PM2.5) was associated with an increased risk of chronic obstructive pulmonary disease (COPD). It remains unclear whether reduced PM2.5 can decrease the risk of COPD development. OBJECTIVE: To investigate the associations of dynamic changes (including deterioration and improvement) in long-term exposure to ambient PM2.5 with changes in lung function and the incidence of COPD. METHODS: A total of 133,119 adults (aged 18 years or older) were recruited in Taiwan between 2001 and 2014. All participants underwent at least two standard medical examinations including spirometry test. We estimated PM2.5 concentrations using a high-resolution (1 km2) satellite-based spatio-temporal model. The change in PM2.5 (ΔPM2.5) was defined as the difference in concentration of PM2.5 between the respective visit and the previous visit. We used a multivariable mixed linear model and time-varying Cox model to investigate the associations of change in PM2.5 with annual change of lung function and the incidence of COPD, respectively. RESULT: The PM2.5 concentration in Taiwan increased during 2002-2004 and began to decrease around 2005. Every 5-µg/m3/year decrease in the annual change of PM2.5 (i.e., ΔPM2.5/year of 5 µg/m3/year) was associated with an average increase of 19.93 mL/year (95 %CI: 17.42,22.43) in forced expiratory volume in 1 s (FEV1), 12.76 mL/year (95 %CI: 9.84,15.66) in forced vital capacity (FVC), 70.22 mL/s/year (95 %CI: 64.69,76.16) in midexpiratory flow between 25 and 75% of the forced vital capacity (MEF25-75), 0.27%/year (95 %CI: 0.21%, 0.32%) in FEV1/FVC/year. Every 5 µg/m3 decrease in PM2.5 (i.e., ΔPM2.5 of 5 µg/m3) was associated with a 12% (95 %CI: 7%, 17%) reduced risk of COPD development. The stratified and sensitivity analyses generally yielded similar results. CONCLUSION: An improvement in PM2.5 pollution exposure was associated with an attenuated decline in lung function parameters of FEV1, FVC, MEF25-75, and FEV1/FVC, and a decreased risk of COPD development. Our findings suggest that strategies aimed at reducing air pollution may effectively combat the risk of COPD development.

Associations of Reduced Ambient PM2.5 Level With Lower Plasma Glucose Concentration and Decreased Risk of Type 2 Diabetes in Adults: A Longitudinal Cohort Study.

It remains unknown whether reduced air pollution levels can prevent type 2 diabetes mellitus. In this study, we investigated the associations between dynamic changes in long-term exposure to ambient fine particulate matter, defined as particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), and changes in fasting plasma glucose (FPG) levels and incidence of type 2 diabetes. A total of 151,398 adults (ages ≥18 years) were recruited in Taiwan between 2001 and 2014. All participants were followed up for a mean duration of 5.0 years. Change in PM2.5 (ΔPM2.5) was defined as the value at a follow-up visit minus the corresponding value at the immediately preceding visit. The PM2.5 concentration in Taiwan increased during 2002-2004 and began to decrease in 2005. Compared with participants with little or no change in PM2.5 exposure, those with the largest decrease in PM2.5 had a decreased FPG level (ß = -0.39, 95% confidence interval: -0.47, -0.32) and lower risk of type 2 diabetes (hazard ratio = 0.86, 95% confidence interval: 0.80, 0.93). The sensitivity analysis and analyses stratified by sex, age, body mass index, smoking, alcohol drinking, and hypertension generally yielded similar results. Improved PM2.5 air quality is associated with a better FPG level and a decreased risk of type 2 diabetes development.

Long non-coding RNA MCF2L-AS1 promotes the aggressiveness of colorectal cancer by sponging miR-874-3p and thereby up-regulating CCNE1.

BACKGROUND: Long non-coding RNAs (lncRNAs) have drawn growing attention because of the role which they play in various diseases, including colorectal cancer (CRC). However, the potential functions of lncRNA MCF2L antisense RNA 1 (MCF2L-AS1) in tumors remained largely unclear. The present study aimed to explore the clinical significance and the biological effects of lncRNA MCF2L antisense RNA 1 (MCF2L-AS1) in CRC. METHODS: Reverse transcriptase-polymerase chain reaction was performed to determine the expression of MCF2L-AS1 in CRC. The clinical significance of MCF2L-AS1 in CRC patients was analyzed statistically. In vitro experiments were performed to determine the effects of MCF2L-AS1 on the cellular progression of CRC cells. Bioinformatic assays, luciferase reporter assays and RNA-pulldown assays were performed to predict for potential microRNAs that can interact with MCF2L-AS1 and mRNAs that can interact with miR-874-3p. RESULTS: We identified a novel CRC-related lncRNA, MCF2L-AS1, which is distinctly highly expressed in CRC. Its diagnostic value for CRC patients was also demonstrated. Clinical assays revealed that high MCF2L-AS1 expression is associated with advanced stages, positive metastasis and the poor prognosis of CRC patients. Multivariate assays confirmed that MCF2L-AS1 expression is an independent poor prognostic factor for both 5-year overall survival and 5-year disease-free survival of CRC patients. Functionally, we confirmed that knockdown of MCF2L-AS1 distinctly suppresses the proliferation, migration and invasion of CRC cells and also promotes apoptosis. Mechanistic investigation showed that MCF2L-AS1 functions as an endogenous sponge for miR-874-3p to increase the expression of CCNE1. CONCLUSIONS: Our findings identified a novel CRC-related lncRNA, MCF2L-AS1, which may be used as a potential diagnostic and prognostic biomarker for CRC patients. In addition, the newly identified MCF2L-AS1/miR-874-3p/CCNE1 axis can modulate the initiation and progression of CRC.

The factors related to failure of Enhanced Recovery after Surgery (ERAS) in colon cancer surgery.

PURPOSE: Enhanced Recovery after Surgery has been proven effective for patients with gastrointestinal cancer. But radical enhanced recovery could also lead to adverse clinical outcomes. Compared with reports on the estimation of successful implementation of enhanced recovery, studies on risk factors of enhanced recovery failure are still lacking. METHODS: A retrospective analysis was carried out on 102 patients in ERAS who underwent elective colon cancer surgery. This study included 102 patients with colon cancer between 2015 and 2019, defining enhanced recovery failure as postoperative length of stay over 10 days, stay in ICU over 24 h after surgery, reoperation, death, or unplanned readmission within 30 days after surgery. Univariate and multivariate analyses were performed to explore potential risk factors of failure. RESULTS: Aged ≥ 75, open operation, number of drainage tube over 1, re-urethral catheterization, and Clavien-Dindo grade over 2 were associated with ERAS failure, according to univariate analysis. Multivariate analysis showed that age ≥ 75 [OR 7.231; P = 0.009]; open operation (OR 3.599; P = 0.021); and number of drainage tube over 1 (OR 3.202; P = 0.020) were independent risk factors for ERAS failure. CONCLUSIONS: We found age ≥ 75, open operation, and number of drainage tube over 1 are independent risk factors associated with ERAS failure after colon cancer surgery.

USP18 directly regulates Snail1 protein through ubiquitination pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common digestive malignant tumors in the world. Ubiquitin-specific peptidase 18 (USP18) plays a regulatory role in tumorigenesis, and abnormal expression of Snail1 is also believed to be related to tumorigenesis. However, whether USP18 could affect colorectal cancer through Snail1 remains unclear. This study was designed to investigate the role of USP18 in colorectal cancer. METHODS: USP18 protein and mRNA abundance in clinical tissues and five cell lines were analyzed with quantitative real-time PCR (qRT-PCR) and western blot. USP18 overexpression-treated DLD1 cells and USP18 knockdown-treated SW480 cells were used to study cell proliferation, migration, invasion, and the expression of epithelial-mesenchymal transformation (EMT) biomarkers. Moreover, ubiquitination-related Snail1 degradation was detected with qRT-PCR and western blot. The relationships between USP18 and Snail1 were investigated with western blot, co-immunoprecipitation, migration, and invasion. RESULTS: USP18 was highly expressed in colorectal cancer tissues. Overexpression of USP18 could promote proliferation, colony formation, migration, and invasion of colorectal cancer cells. Overexpression of USP18 effectively promoted cell survival after treatment with three different chemotherapy drugs. Moreover, USP18 could regulate Snail1 degradation through ubiquitination pathway. Furthermore, we demonstrated that Snail1 could effectively reverse the influence of USP18 on cell proliferation, migration, invasion, and EMT of CRC cells. CONCLUSION: USP18 could promote the proliferation, migration, and invasion of colorectal cancer by deubiquitinating and stabilizing the Snail1 protein in colorectal cancer.

Independent and Opposing Associations of Habitual Exercise and Chronic PM2.5 Exposures on Hypertension Incidence.

BACKGROUND: We investigated the joint associations of habitual physical activity (PA) and long-term exposure to fine particulate matter (PM2.5) with the development of hypertension in a longitudinal cohort in Taiwan. METHODS: We selected 140 072 adults (≥18 years of age) without hypertension who joined a standard medical screening program with 360 905 medical examinations between 2001 and 2016. PM2.5 exposure was estimated at each participant's address using a satellite data-based spatiotemporal model with 1 km2 resolution. Information on habitual PA and a wide range of covariates was collected using a standard self-administered questionnaire. We used the Cox regression model with time-dependent covariates to examine the joint associations. RESULTS: The mean age of all observations was 41.7 years, and 48.8% were male. The mean value for systolic and diastolic blood pressure was 112.5 and 68.7mm Hg, respectively. Approximately 34.2% of all observations were inactive (0 metabolic equivalence values-hours), 29.8% had moderate-PA (median [interquartile range]; 3.75 [3.38 to 4.38] metabolic equivalence values-hours), and 36.0% had high-PA (15.7 [10.3 to 24.8] metabolic equivalence values-hours). The mean±SD of PM2.5 was 26.1±7.3 µg/m3. The prevalence of cardiovascular disease, diabetes mellitus, and cancer was 2.1%, 2.9%, and 1.5%, respectively. After adjusting for a wide range of covariates (including a mutual adjustment for PA or PM2.5), a higher PA level was associated with a lower risk of hypertension (hazard ratio [HR] for the moderate- and high-PA was 0.93 [95% CI, 0.89-0.97] and 0.92 [95% CI, 0.88-0.96], respectively, as compared with the inactive-PA), whereas a higher level of PM2.5 was associated with a higher risk of hypertension (HR for the moderate- and high-PM2.5 was 1.37 [95% CI, 1.32-1.43] and 1.92 [95% CI, 1.81-2.04], respectively, as compared with the low-PM2.5 group]. No significant interaction was observed between PA and PM2.5 (HR 1.01 [95% CI, 1.00-1.02]). CONCLUSIONS: A high-PA and low PM2.5 exposure were associated with a lower risk of hypertension. The negative association between PA and hypertension remained stable in people exposed to various levels of PM2.5, and the positive association between PM2.5 and hypertension was not modified by PA. Our results indicated that PA is a suitable hypertension prevention strategy for people residing in relatively polluted regions.

Long-term exposure to ambient fine particles and gastrointestinal cancer mortality in Taiwan: A cohort study.

BACKGROUND: Information on the association between long-term exposure to PM2.5 and gastrointestinal cancer mortality is scarce. OBJECTIVES: This study investigated the association between long-term exposure to PM2.5 and deaths from gastrointestinal cancer and its subtypes in adults in Taiwan. METHODS: A total of 385,650 Taiwanese adults (≥18 years old) jointed a standard medical examination program between 2001 and 2014 and were followed up until 2016. Their vital data were obtained from the National Death Registry maintained by the Ministry of Health and Welfare in Taiwan. We estimated the ambient PM2.5 concentration at individual's address utilising a satellite-based spatiotemporal model at a resolution of 1 km2. Cox proportional hazard regression model was used to investigate the associations between ambient PM2.5 and deaths from gastrointestinal, stomach, colorectal and liver cancers. RESULTS: We found that each 10 µg/m3 increase in PM2.5 was associated with an increased hazard risk (HR) of 1.09 (95% confidence interval (CI): 1.03-1.16) and 1.13 (95%CI: 1.02-1.24) in deaths from gastrointestinal and liver cancers, respectively. The association between PM2.5 and death from colorectal cancer was marginally statistically significant [HR: 1.13 (95%CI: 1.00-1.26)]. We did not find significant associations between PM2.5 and mortality from stomach cancer. CONCLUSIONS: Long-term exposure to ambient PM2.5 was associated with an increased risk of deaths from gastrointestinal cancers, liver cancer and also potentially colorectal cancer. Air pollution control strategies are necessary to reduce the burden of gastrointestinal cancer.