Objective To investigate the potential therapeutic effects of trifolin on hypertension-induced renal injury,as well as the key targets and pathways involved.Methods The mRNA transcriptional profiles of peripheral blood clinical samples from hypertensive patients were analyzed using Gene Expression Omnibus(GEO),a high-throughput gene expression database.The network pharmacology method was employed to screen key targets of trifolin in treating hypertension-induced renal injury.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted.NRK-52E cells,a rat renal proximal tubular cell line,were used to construct an angiotensin Ⅱ(Ang Ⅱ)-stimulated cell model.Flow cytometry was performed to assess cell apoptosis rates and Western blotting was performed to determine the expression levels of apoptosis-related proteins,including Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the phosphorylation and total protein levels of the key MAPK pathway proteins,including ERK,p38 MAPK,and JNK.Results Analysis of the dataset GSE75360 revealed that,compared with healthy controls,3 331 genes were upregulated and 3 197 genes were downregulated in peripheral blood mononuclear cells of hypertensive patients.According to network pharmacology analysis,472 potential targets of trifolin were identified,including CASP3 and MAPK1.Protein-protein interaction network analysis showed that these targets were closely associated with apoptosis regulatory signaling pathways.GO and KEGG pathway enrichment analyses indicated that trifolin was significantly enriched in pathways associated with negative regulation of apoptosis,apoptotic signaling pathways,and the MAPK signaling pathway.The in vitro experiments confirmed that,compared with the Ang Ⅱ group,trifolin intervention inhibited apoptosis in Ang Ⅱ-stimulated NRK-52E cells,suppressed the expression of Bax and cleaved caspase-3,promoted Bcl-2 expression,and inhibited the phosphorylation of p38 MAPK,ERK,and JNK(P<0.05).Conclusion Trifolin may exert its protective effect against hypertension-induced renal injury by inhibiting Ang Ⅱ-induced NRK-52E cell apoptosis and regulating the MAPK signaling pathway,representing an important mechanism underlying its therapeutic action.

Background Nitrogen dioxide (NO₂) is one of the main air pollutants, and though China's NO₂ pollution has been improving year by year, it maintains at a high level, threatening the health of the population. Objective To investigate the effect of short-term exposure to atmospheric NO₂ on the coagulation indexes in obese and normal-weight young individuals and potential modification effect of temperature. Methods Based on a parallel control panel study design, this study recruited 53 normal-weight and 44 obese young individuals. Three prospective follow-ups were conducted. Air pollution data were obtained from the fixed monitoring station closest to the participant's residences, and personal air pollution exposure was simulated based on time-activity log and infiltration factor for the week before every follow-up. Temperature was collected from China Meteorological Data Service Center. Venous blood samples were taken to measure platelet (PLT) count, mean platelet volume (MPV), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), platelet aggregation rate (PAgT), and plasminogen activator inhibitor type-1 (PAI-1) during every follow-up. A linear mixed-effect model was used to assess the association between short-term atmospheric NO₂ exposure and the coagulation indexes of weight grouped young individuals, and a stratified analysis was used to explore potential modification effect of temperature. Results The median [interquartile range (IQR)] of personal atmospheric NO₂ exposure concentrations was 21.47 (8.01) µg·m⁻³. Short-term exposure to atmospheric NO₂ was significantly associated the increase of sCD40L and PAgT in the obese individuals, while the most significant association appeared at 5 d lag, and for each IQR increase in the average sliding exposure concentration of atmospheric NO₂ with a 5 d lag, sCD40L increased by 27.4% (95%CI: 4.2%, 56.6%) and PAgT increased by 37.5% (95%CI: 12.2%, 68.6%); short-term exposure to atmospheric NO₂ was significantly associated with the decrease of PLT and PAgT in the normal-weight individuals, while the most significant association appeared at 5 d lag or 7 d lag, and for each IQR increase in the average sliding exposure concentration of atmospheric NO₂ with a 5 d lag, PLT decreased by 11.8% (95%CI: −17.8%, −5.3%), and for each IQR increase in the average sliding exposure concentration of atmospheric NO₂ with a 7 d lag, PAgT decreased by 16.8% (95%CI: −30.6%, −0.4%). We didn't find statistically significant association of short-term exposure to atmospheric NO₂ with PLT in the obese individuals or sCD40L in the normal-weight individuals, nor statistically significant association between short-term exposure to atmospheric NO₂ and PAI-1, MPV, and sP-selectin in different weight grouped individuals. The stratified analysis found that short-term exposure to atmospheric NO₂ was significantly associated with PAgT in the normal-weight individuals, or with PLT, sCD40L, and sP-selectin in the obese individuals only at high temperature. Conclusions Short-term exposure to atmospheric NO₂ has adverse effects on the coagulation indexes of different weight grouped young individuals, and the obese individuals are more sensitive to it than the normal-weight individuals. High temperature can enhance the adverse health effect of short-term exposure to atmospheric NO₂.

Objective:To investigate personal exposures to nitrogen oxides(NOX)and nitrogen di-oxide(NO2)and the influence of baseline personal characteristics,living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai.Methods:In this panel study,91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study.The study was conducted in summer and winter.The participants were followed for three times with an interval of at least two weeks.Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic.Twenty-seven participants completed follow-up visits in both seasons.We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity in-formation through questionnaire/diary.The linear mixed model was used to analyze the associations be-tween potential influencing factors and personal NOX and NO2 exposure levels.Results:There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities.The ave-rage 24 h personal exposures to NO2 and NOX(volume fraction)in Tianjin participants were 18.0 x 10-9 and 26.2 × 10-9 in summer,and 31.0 x 10-9 and 54.9 x 10-9in winter,respectively;and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7 x 10-9and 100.0x10-9in summer,and 45.5 x10-9 and 139.2 x 10-9 in winter,respectively.The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city,season,gender,average daily cooking times,and ambient NO2 concentrations measured at fixed-site monitoring stations.In addition to the above factors,the personal NOX exposure levels were also significantly associ-ated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking,average daily home time,cooking energy type,residential distance from main traffic road,and use of kitchen ventilators.Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai,were significantly lower in summer than that in winter,and were significantly and positively associated with ambient NO2 concen-trations measured at fixed-site monitoring stations.In addition,personal NOX exposure levels were signifi-cantly lower in females than in males,and personal NO2 exposure levels were significantly positively asso-ciated with average daily cooking times and significantly inversely associated with average daily home time.For every interquartile range(IQR)increase(12.7 × 10-9)in ambient NO2,the personal NO2 exposure levels increased by 27.5％(95％CI:17.0％-38.9％),and personal NOX exposure levels in-creased by 16.1％(95％CI:7.1％-25.8％).Conclusion:Season,city and ambient NO2 concentra-tions are significant influencing factors of personal exposure levels of NO2and NOX At the same time,the personal exposures levels of NO2 are also affected by lifestyle factors.Our study provides scientific evi-dence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.

Background The health effects of forest therapy have been widely recognized, while the previous studies mostly focused on a single activity mode of forest walks. The effects of different types of forest therapy activities remain unclear. Objective To explore the effects of short-term forest therapy on cardiopulmonary health, psychological health, and sleep quality, and the health effects of different types of forest therapy activities, aiming to provide population empirical study data for the development of forest therapy. Methods A self-control study was conducted in a national forest park in suburb of Beijing from August to September 2018. A total of 31 healthy college students were recruited as the study subjects, with a total forest stay for 3 days and 2 nights. During the period of study, each subject practiced walking therapy, sitting therapy with five senses experience (sitting therapy thereafter), and handmade work therapy, successively. Each type of forest therapy lasted about 2 h. Changes of blood pressure, oxygen saturation (SpO₂), lung function, and fractional exhaled nitric oxide (FeNO) were estimated by measuring corresponding indicators before and after the forest therapy. Psychological health and sleep quality were assessed by Profile of Mood States and Pittsburgh Sleep Quality Index respectively at the same time. Mixed effects models were used to analyze the changes of these health indicators. The health effects of different types of forest therapy activities were further analyzed. Results The average age and body mass index of subjects in this study were (24.5±2.6) years and (20.7±1.7) kg·m⁻², respectively. After a short-term forest therapy, the selected indicators of cardiopulmonary health, psychological health, and sleep quality of subjects were all improved. In particular, the pulse pressure (PP) and FeNO decreased by 3.02 mmHg and 1.10 ppb, respectively, while the SpO₂ and peak expiratory flow (PEF) increased by 0.65% and 0.50 L·s⁻¹, respectively, and the negative emotion and global sleep quality also presented significant positive changes (all P<0.05). Furthermore, different therapy activities presented differential effects in the health indicators. Walking therapy significantly improved pulmonary function, SpO₂, and confusion (CON) emotion, in which the SpO₂, forced expiratory volume in the first second (FEV₁), and forced vital capacity (FVC) increased by 0.48%, 0.14 L, and 0.12 L, respectively, and the score of CON decreased by 0.97 (all P<0.05). Sitting therapy significantly reduced blood pressure and tension (TEN) emotion of subjects, including a decrease of the systolic blood pressure (4.45 mmHg), PP (4.19 mmHg), and the score of TEN (0.84) (all P<0.05). The diastolic blood pressure (DBP) increased slightly after handmade work therapy (ΔDBP=2.44 mmHg, P=0.016), but there were no significant changes in other indicators. Conclusion Short-term forest therapy could significantly improve cardiopulmonary health, psychological health, and sleep quality of young healthy individuals, and different types of forest therapy activities may have differential health effects.

Background Exposure to ambient nitrogen dioxide (NO₂) could increase the risks of small for gestational age (SGA) and large for gestational age (LGA). Nevertheless, previous published studies usually use a time period over relatively long durations as the exposure window, such as trimester-specific or gestational months, to identify adverse pregnancy outcomes related susceptible exposure windows for ambient air pollution. At present, no study has explored associations of weekly-specific ambient air NO₂ exposure around pregnancy with SGA and LGA. Objective To evaluate the associations of exposure to ambient NO₂ over the preconception and entire pregnancy period with risks of SGA and LGA, as well as to explore critical windows of NO₂ exposure by refining exposure period to specific weeks. Methods Based on a birth cohort established by the project Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) situated in Tianjin, 10 916 singleton pregnant women whose dates of the last menstrual period and delivery were both between June 2014 and June 2016, and whose gestational age were within 24-42 completed gestational weeks were included in this study. Each pregnant woman's exposures to ambient NO₂ throughout 12 weeks before pregnancy and pregnancy period were matched with daily average NO₂ concentrations obtained from the Chinese air quality reanalysis datasets (CAQRA). Distributed lag models incorporated in Cox proportional hazard regression models were applied to explore the associations of maternal exposure to weekly ambient NO₂ throughout 12 weeks before pregnancy and pregnancy period with risks of SGA and LGA after controlling for potential confounders including maternal age, ethnicity, educational level, occupation, body mass index before pregnancy, residence, times of gravidity and parity, smoking, alcohol consumption, husband smoking, and season of conception. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated per 3 μg·m⁻³ increase in ambient NO₂ concentrations. Results The average levels of maternal exposure to NO₂ over the preconception, first trimester, second trimester, third trimester, and entire pregnancy periods were (39.6±10.8), (42.7±10.5), (44.8±12.7), (37.7±11.1), and (41.6±4.8) μg·m⁻³, respectively. For a 3 μg·m⁻³ increase in NO₂ over the first trimester, the risk of SGA increased by 19.0% (95%CI: 8.0%-32.0%). For a 3 μg·m⁻³ increase in NO₂ over the preconception, first trimester, and entire pregnancy, the associated risks of LGA increased by 7.0% (95%CI: 1.0%-13.0%), 37.0% (95%CI: 29.0%-46.0%) and 19.0% (95%CI: 9.0%-31.0%), respectively. For SGA, the susceptible exposure windows for NO₂ were observed during the 7^th to 12^th preconceptional weeks and the 6^th to 12^th gestational weeks, with the strongest association found at the 12^th preconceptional week, when the risk of SGA increased by 6.0% (95%CI:3.2%-8.9%) for a 3 μg·m⁻³ increase in NO₂. For LGA, the susceptible exposure windows for NO₂ were observed during the 1^st to 12^th preconceptional weeks and the 1^st to 6^th gestational weeks, with the strongest association found at the 12^th preconceptional week, when the risk of LGA increased by 6.1% (95%CI: 4.5%-7.8%) for a 3 μg·m⁻³ increase in NO₂. Conclusion Exposure to ambient NO₂ is associated with increased risks of both SGA and LGA, and the most susceptible weekly exposure windows are nested within the 12 weeks before pregnancy and early pregnancy.

Humans ; Air Pollutants ; Sleep Apnea, Obstructive ; Polysomnography ; Sleep ; Pulmonary Disease, Chronic Obstructive

Objective: To assess the associations of indoor fine particulate matter (PM_2.5) from outdoor and indoor sources with heart rate (HR) and heart rate variability (HRV) in patients with chronic obstructive pulmonary disease (COPD) of Beijing. Methods: A total of 40 male patients in a stable stage of COPD were recruited from a hospital in a panel study in Beijing with 5 consecutive days of measurement for each subject. General information and disease history of the participants from questionnaires were obtained prior to the study. HR and HRV were repeatedly examined using dynamic electrocardiograph. HRV included standard deviation of all NN intervals (SDNN), root mean square of successive differences between adjacent NN intervals (rMSSD), total power (TP) power in the low-frequency band (LF) and the high-frequency band (HF). Iron was used as tracer element to separate indoor-originated PM_2.5 and outdoor-originated PM_2.5. Mixed-effect models were applied to assess the associations of outdoor-originated PM_2.5 or indoor-originated PM_2.5 and health effects. Results: The P₅₀ (P₂₅, P₇₅) values of daily indoor PM_2.5, indoor-originated PM_2.5 and outdoor-originated PM_2.5 were 50.9 (26.8, 122.7), 16.0 (1.9, 43.7) and 27.3 (13.5, 61.8) μg/m³, respectively. The mean±SD of concentrations of real-time indoor PM_2.5, indoor-originated PM_2.5 and outdoor-originated PM₂.5 were (61.5±58.8), (25.3±39.1) and (36.2±42.7) μg/m³, respectively. Compared with outdoor-originated PM_2.5, indoor-originated PM_2.5 had significant associations with HRV and HR. Each 10 μg/m³ increase at 4 h indoor-originated PM_2.5 and outdoor-originated PM_2.5 moving average was associated with 3.4% (95%CI: -4.7%, -2.1%) and 0.6% (95%CI: -2.0%, -0.8%) reduction in TP (P<0.001). Each 10 μg/m³ increase at 12 h indoor-originated PM_2.5 moving average was associated with 7.6% (95%CI: -10.1%, -5.1%), 4.7% (95%CI: -6.7%, -2.7%), 3.3% (95%CI: -4.2%,-2.4%) and 3.0% (95%CI: -4.5%, -1.5%) reduction in HF, LF, SDNN and rMSSD, respectively. Each 10 μg/m³ increase at 12 h outdoor-originated PM_2.5 moving average was associated with 0.7% (95%CI: -2.7%, -1.4%), 0.2% (95%CI: -1.9%, 1.4%), 0.7% (95%CI: -1.4%, -0.1%) and 0.2% (95%CI: -1.3%, 0.9%) reduction in HF, LF, SDNN and rMSSD, respectively (P<0.001). Each 10 μg/m³ increase at 8 h indoor-originated PM_2.5 and outdoor-originated PM_2.5 moving average was associated with 0.7% (95%CI: 0.4%, 1.0%) and 0.4% (95%CI: 0.2%, 0.6%) increase in HR. Conclusion Exposure to indoor-originated PM_2.5 was more strongly associations with HRV indices and HR compared with outdoor-originated PM_2.5 in male COPD patients.

Objective To explore the effect of carbon monoxide (CO) and ozone (O3) in the air on the myocardial infarction mortality in Ningbo,Zhejiang province,from 2011 to 2015.Methods The data of daily air quality surveillance and the causes of deaths in Ningbo from January 1,2011 to December 31,2015 were collected and the time series study using a generalized additive model was conducted to evaluate the relationship between the mortality of myocardial infarction and the air pollutants after adjustment for the long-term trend of death,weather conditions,"days of the week" and other confounding factors.Results The daily average concentrations of CO and O3 in Ningbo during 2011-2015 were 0.90 (0.02-3.31) mg/m3 and 82.78 (4-236) μg/m3,respectively.A total of 5 388 myocardial infarction deaths occurred,with a daily average of 3 deaths.In single-pollutant model,an increase of 0.1 mg/m3 in average concentration of CO could increase the risk of myocardial infarction mortality by 1.06％ (95％ CI:0.29％-1.93％) in general population,and by 1.26％ (95％ CI:0.28％-2.24％) in aged people aged ≥65 years in lagged 6 days,but the influence was not significant in people aged ＜65 years.The influence had no significant difference in males,but it increased the risk of myocardial infarction mortality by 1.77％ in females (95％ CI:0.44％-3.13％).In multipollutant model,CO did remain robust after adjusting for other co-pollutants.Whereas the effect of O3 had no significant influence.Conclusion These findings suggested that the increased risk of daily myocardial infarction mortality was associated with the increase of CO concentration,but no such association was found for O3 in Ningbo.

Objectives: To investigate the effect of short-term exposure to ambient NO₂ has influence on lung function and fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) patients. Methods: A panel of doctor-diagnosed stable COPD patients (n=33) were recruited and repeatedly measured for lung function and FeNO from December 2013 to October 2014. The patients who lived in Beijing for more than one year and aged between 60 and 85 years old were included in the study. We excluded patients with asthma, bronchial tensor, lung cancer and other respiratory disorders other than chronic obstructive pulmonary disease and occupational exposure and chest trauma surgery patients. Because the frequency of each subject visiting to the hospital was different, a total of 170 times of lung function measurements and 215 times of FeNO measurements were conducted. At the same time, the atmospheric NO₂ data of Beijing environmental monitoring station near the residence of each patient during the study period were collected from 1 day to 7 days lag before the measurement. Effects of short-term NO₂ exposure on lung function and FeNO in COPD patients were estimated by linear mixed-effects models. Results: The subjects' forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), peak expiratory flow (PEF), and exhaled NO of subjects were (3.26±0.83) L, (1.66±0.61) L, (4.13±1.77) L/s, and (48.99±14.30) μg/m³, respectively. The concentration of NO₂ was (70.3±34.2) μg/m³ and the interquartile range (IQR) was 39.0 μg/m³. Short-term exposure to NO₂ resulted in a significant decrease in FVC among COPD patients' which was most obvious in 2 days lag. Every quartile range increased in NO₂ (39 μg/m³, 2 day) would cause a 1.84% (95%CI: -3.20%- -0.48%) reduction in FVC. The effects of exposure to higher concentration of NO₂ (≥58.0 μg/m³) on FVC estimate was -2.32% (95%CI: -4.15%- -0.48%)(P=0.02). No significant relevance of FeNO and NO₂ was observed in this study. Conclusions Short term exposure to ambient NO₂ may bring down pulmonary function in COPD patients.

Objective: To investigate the effect of silver nanoparticles (AgNPs) on hemichannel activity in human skin keratinocytes (HaCaT) and to explore the role of hemichannel in AgNP-induced anti-proliferative effect on HaCaT cells.Methods: HaCaT cells were exposed to 0, 0.1, 0.2, 1.0, 5.0, 10.0, 15.0 and 20.0 μg/cm2 of AgNPs for 24 h and cell viability was assessed by propidium iodide (PI) staining with flow cytometry.Hemichannel activity was examined by ethidium bromide (EB) uptake experiments in cells exposed to AgNPs with and without hemichannel inhibitor carbenoxolone (CBX).Afterward, HaCaT cells were seeded at a low density of 1×104cell /cm2 or a normal density of 4×104cell /cm2 and cultured for 24 h.Cell proliferation was measured by cell counting kit-8 (cck-8) in low-or normal-density cultured cells exposed to AgNPs for 24 h with and without 100 μmol/L CBX.Results: Cell viability showed no significant differences between the control and AgNP-exposed groups with the concentration less than 10 μg/cm2.Exposure to AgNPs increased EB uptake in a time-and dose-dependent manner in HaCaT cells and EB fluoresce density was increased to 116.67%, 124.85% and 139.53% of the control after exposure to 10 μg/cm2 AgNPs for 2 h, 12 h and 24 h.After being treated with 25, 50 and 100 μmol/L CBX, 10 μg/cm2 AgNP-induced increase in EB uptake was significantly reduced in HaCaT cells (P<0.01).The cellular proliferation rate was increased inlow-and normal-density cultured cells after AgNPs exposure with 100 μmol/L CBX.After being treated with 100 μmol/L CBX, 10 μg/cm2 AgNP-induced anti-proliferation in low-density cultured cells was significantly restrained (P<0.01).Conclusion: AgNPs could enhance hemichannel activity of HaCaT cells.Hemichannel activation was involved in AgNP-induced anti-proliferative effect.