Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

With the accelerating aging of world population, the prevalence and disease burden of dementia such as Alzheimer's disease is increasing annually. As one of the major risk factors for dementia, air pollution is still an urgent global concern. Studies on the association between ambient particulate matter (PM), one of the major air pollutants, and dementia, such as Alzheimer's disease, are gaining attention. This paper reviewed the current evidence of relevant epidemiological and toxicological studies to illustrate the possible mechanisms underlying the effects of PM exposure on Alzheimer's disease through inflammatory responses, oxidative stress, endocrine disruption, excitatory neurotoxicity, glial cell activation, and intestinal flora disruption, which may provide clues for mitigating the health risks of air pollution and preventing Alzheimer's disease.

Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON₃ group), 7-day control group (CON₇ group), 3-day oil fume exposure group (COF₃ group), and 7-day oil fume exposure group (COF₇ group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4⁺ and CD8⁺T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF₃ group and the COF₇ group were significantly increased (P<0.05) except IL-6 in the COF₃ group, and the levels in the COF₇ group were significantly higher than those in the COF₃ group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF₇ group after HE staining. The flow cytometry results showed that the proportions of CD4⁺ and CD8⁺T cells in adipocytes of the COF₃ group and the COF₇ group were increased compared to the corresponding control group, with a significant increase in the COF₇ group (P<0.05), and the CD4⁺/CD8⁺T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF₃ group and the COF₇ group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF₃ group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF₇ group were significantly higher than those in the CON₇ group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.

Background It is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. Objective To observe the effects of combined exposure to PM_2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. Methods A total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (T_N-FA), a normal temperature-concentrated PM_2.5 group (T_N-PM), a heat-filter air group (T_H-FA), a heat-concentrated PM_2.5 group (T_H-PM), a cold-filter air group (T_C-FA), and a cold-concentrated PM_2.5 group (T_C-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM_2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. Results The transcriptomics results indicated that the PM_2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the T_N-PM mice compared to the T_N-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM_2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM_2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P<0.01, P<0.05) and a significant decrease in the expression of GLUT4 (P<0.05, P<0.01). In skeletal muscle, exposure to PM_2.5 led to a significant decrease in GLUT4 (P<0.05) in all environments, with a consistent trend of change as observed in WAT. Conclusion Cold/heat exposure might promote PM_2.5-induced metabolic disorder through suppression of the AKT/GLUT4 pathway, aggravating metabolic damage.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

Objective:To compare the efficacy and safety of cap-assisted endoscopic sclerotherapy (CAES) and procedure for prolapse and hemorrhoids (PPH) for internal hemorrhoids.Methods:This study was a prospective double-blind controlled clinical one. A total of 80 patients with internal hemorrhoids who visited Baoding No.1 Central Hospital from March 2018 to March 2020 and met the inclusion and did not meet exclusion criteria, were randomly divided into CAES group ( n=40) and PPH group ( n=40) by random number table method, and received corresponding treatment respectively. The perioperative indices of the two groups were compared, including intraoperative blood loss, operation time, visual analogue scale (VAS) score at 24 and 48 hours after operation, length of hospital stay, treatment costs, time to return to normal life, and curative rates. The complications within 3 months after operation and the 1-year recurrence after operation were also compared between the two groups. Results:The operation was successfully completed in all patients. The intraoperative blood loss (0.54±0.15 mL VS 7.32±2.17 mL) and treatment cost (6 249.53±435.67 yuan VS 7 832.96±526.74 yuan) in CAES group were significantly lower than those in PPH group ( t=19.714, P<0.05; t=14.650, P<0.05). The length of hospital stay (3.53±0.94 d VS 5.18±1.36 d) and time to return to normal life (5.26±1.28 d VS 7.17±2.09 d) in CAES group were significantly lower than those in PPH group ( t=6.312, P<0.05; t=4.929, P<0.05). There was no significant difference in operation time between the two groups ( t=0.977, P>0.05). The VAS scores at 24 h (2.64±0.70 points VS 3.59±0.93 points) and 48 h (1.28±0.31 points VS 2.16±0.57 points) after operation in CAES group were significantly lower than those in PPH group ( t=5.162, P<0.05; t=8.578, P<0.05). There was no significant difference in the curative rate [90.0% (36/40) VS 97.5% (39/40)] between CAES group and PPH group ( χ2=0.853, P=0.356). During the follow-up period within 3 months after the operation, the incidence of urinary retention [0.0% (0/40) VS 15.0% (6/40)] and pain [2.5% (1/40) VS 22.5% (9/40)] in CAES group was significantly lower than those in PPH group ( χ2=4.504, P<0.05; χ2=7.314, P<0.05). No other complications occurred in the 80 patients. After 1 year of follow-up, the recurrence rate of CAES group was 7.5% (3/40), which was not statistically different from that in PPH group [5.0% (2/40), χ2=0.180, P>0.05]. Conclusion:As a new minimally invasive technique for the treatment of internal hemorrhoids, CAES has similar curative rate and 1-year recurrence rate to PPH. Compared with PPH, CAES shows the advantages of less trauma, less pain, faster recovery and lower cost.

Objective: To investigate the health effects of air pollution on elementary school students with the indicator of absenteeism caused by respiratory symptoms and diseases, and to provide a reference for improving their physical health. Methods: Absenteeism, air pollutants, and meteorological data during Sep. 2015 to Jun. 2017 in Pudong, Shanghai were collected. Generalized additive model was used to estimate the effects of air pollution on students’ absenteeism caused by respiratory symptom and diseases, time trends, day of week and meteorological factors were controlled. Results: Totally 47 723 person-days of elementary school students’ absenteeism caused by respiratory symptoms and diseases were recorded during Sep.2015 to Jun. 2016 in Pudong, Shanghai, and the absenteeism rate was 0.07%. The PM2.5 concentration on lag0 and SO2 concentration on lag2 showed the most significant effects, the elementary school students’ absenteeism raised for 1.43% (95%CI=0.25%~2.62%)and 6.79% (95%CI=0.25%~13.32%) respectively with every 10 μg/m3 increment of PM2.5 and SO2. Conclusion Air pollution in Pudong new area have made a influence on the elementary school student’s respiratory symptoms and absenteeism, and the prevention work of air pollution should be strenghthened.