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.

Objective To investigate the role of multimodal magnetic resonance imaging(MRI)features in predicting vascular invasion and prognosis in cervical cancer.Methods A total of 180 cervical cancer patients were included in this study.According to the postoperative vascular invasion status,patients were categorized into vascular invasion-positive group(n=61)and vascular invasion-negative group(n=119).All patients underwent comprehensive MRI protocols including diffusion-weighted imaging(DWI),diffusion tensor imaging(DTI),and dynamic contrast-enhanced MRI(DCE-MRI)scans to analyze intergroup differences in imaging parameters.The diagnostic efficacy of multimodal MRI(DWI,DTI,and DCE-MRI)in detecting vascular invasion and predicting prognosis was evaluated.Results Statistically significant differences in ADCDWI were observed between vascular invasion-positive group and vascular invasion-negative group(P<0.01).The vascular invasion-positive group exhibited significantly lower ADCDTI and FA as compared with vascular invasion-negative group,accompanied by elevated Ktrans,VE,and Kep(P<0.01).Compared with survival group,non-survivor group demonstrated higher ADCDWI,Ktrans,VE and Kep,alongside lower ADCDTI and FA.The sensitivity of multimodal MRI for vascular invasion detection and mortality prediction was higher than that of unimodal detection approaches.Conclusion Multimodal MRI features have significant predictive value for vascular invasion and prognosis in cervical cancer,serving as a critical foundation for clinical decision-making.

Objective To investigate the role of multimodal magnetic resonance imaging(MRI)features in predicting vascular invasion and prognosis in cervical cancer.Methods A total of 180 cervical cancer patients were included in this study.According to the postoperative vascular invasion status,patients were categorized into vascular invasion-positive group(n=61)and vascular invasion-negative group(n=119).All patients underwent comprehensive MRI protocols including diffusion-weighted imaging(DWI),diffusion tensor imaging(DTI),and dynamic contrast-enhanced MRI(DCE-MRI)scans to analyze intergroup differences in imaging parameters.The diagnostic efficacy of multimodal MRI(DWI,DTI,and DCE-MRI)in detecting vascular invasion and predicting prognosis was evaluated.Results Statistically significant differences in ADCDWI were observed between vascular invasion-positive group and vascular invasion-negative group(P<0.01).The vascular invasion-positive group exhibited significantly lower ADCDTI and FA as compared with vascular invasion-negative group,accompanied by elevated Ktrans,VE,and Kep(P<0.01).Compared with survival group,non-survivor group demonstrated higher ADCDWI,Ktrans,VE and Kep,alongside lower ADCDTI and FA.The sensitivity of multimodal MRI for vascular invasion detection and mortality prediction was higher than that of unimodal detection approaches.Conclusion Multimodal MRI features have significant predictive value for vascular invasion and prognosis in cervical cancer,serving as a critical foundation for clinical decision-making.

Objective To explore the effect of oral-muscle biofeedback system training on the rehabilitation of cognitive dysfunction in patients with obstructive sleep apnea (OSA) after ischemic stroke.Methods A total of 60 cases of poststroke OSA patients with cognitive dysfunction admitted to the rehabilitation center of deAn hospital in changzhou city from June 2017 to March 2018 were selected.On the basis of routine rehabilitation treatment,the control group was given positive pressure ventilation treatment,and the observation group was given oral muscle biofeedback system training.The changes of polysomnography (PSG) parameters,Montreal cognitive assessment (MoCA) score,serum matrix metalloproteinase-9 (MMP-9) and plasma homcysteinemia (Hcy) expression levels in the two groups before and after treatment were compared.Results Apnea hypopnea index and maximum apnea time of the two groups were significantly decreased after treatment compared with those before treatment,and the lowest SpO2 and average SpO2 were significantly higher than those before treatment(P＜0.05).After treatment,MoCA total score and the dimensions score of patients in the observation group were significantly higher than those in the control group at the same time (P＜0.05).After treatment,the levels of Hcy((12.38±4.54) μmol/L) and MMP-9((124.52± 12.94) μg/L) in the observation group were significantly lower than those in the control group at the same time(Hcy(17.52±6.27) μmol/L,MMP-9(268.25±20.5 7)μg/L),and the difference was statistically significant (Hcy:t=3.637,P＜0.05;MMP-9:t =32.395,P＜0.05).Conclusions Positive pressure ventilation and oral muscle biofeedback system training have the same effect on OSA after stroke,but oral muscle biofeedback system training can also effectively improve patients' cognitive function.

Objective To explore the relationship between differentially expressed miR-19b-3p and cognitive function in patients with Alzheimer's disease (AD).Methods The miRNA expression profiles of patients with AD(AD group,n=30) or healthy elderly people (NC group,n=30) were analyzed by Illumina/Solexa high-throughput sequencing technique.The miRNA lentiviral plasmids were constructed and injected into the model of AD rats.The cognitive function of rats was analyzed with water maze test.The mimics and inhibitors were synthesized and transfected into SH-SY5Y cell lines.The protein expression of β-amyloid precursor protein cleavage enzyme 1 (BACE1) was detected by western blot.Results Compared with the NC group,the expression of miR-146a-5p (log2AD/Control =2.3),miR-195-5p (log2 AD/Control =10.2),miR-20b-5p(log2AD/Control =15.1) in serum of AD group was up-regulated and the expression of miR-19b-3p (log2 AD/Control =-8.0) and miR-125b-3p (log2 AD/Control =-15.3) was down-regulated (P＜ 0.05).Compared with the rats in the AD group((26.50±3.12) s),the rats in the AD+miR-19b-3p group ((15.33±2.78) s) showed significantly shorter escape latencies(P＜0.05).Compared with the NC group,the protein expression of BACE1 in miR-19b-3p mimetic group was decreased and the protein expression of BACE1 in inhibitor group was increased.Conclusion miR-19b-3p may improve the cognitive function of AD patients via regulating the expression of BACE1.

Objective To explore the optimized scanning parameters of low-dose un-enhanced chest CT with sinogram affirmed iterative reconstruction (SAFIRE).Methods Eleven healthy adult domestic dogs underwent chest scanning of 120 kV,100 kV,80 kV,70 kV with a fixed tube current of 65 mA and halved tube current of 32 mA with a fixed tube voltage of 100 kV.The data were reconstructed with filtered back projection (FBP)and SAFIRE (strength grade 3)respectively to obtain ten groups of images.The regular dose (120 kV/65 mA ) combining with FBP reconstruction was as normal control group,and other groups as experimental groups.CT dose index (CTDI), dose length product (DLP),and effective dose (ED)at different dose were compared,and average CT value,noise,signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)and image quality score of ten groups of images were comparatively analyzed.Results No significant differences were found in average CT value for lung tissue,the superior vena cava,the aortic arch,and spinal muscles among ten groups (P >0.05),except adipose tissue (P <0.05).Compared to the control group,radiation dose of the 100 kV/65 mA-SAFIRE group decreased by 40.00%,noise of this group reduced,SNR and CNR increased,image quality score was slightly higher.Radiation dose of 80 kV/65 mA and 100 kV/32 mA groups,compared to the control group,decreased by 71.33% and 70.00% respectively ;image quality was slightly degraded but the subjective image quality scores were above 4 ,which on the latter group was slightly higher than that on the former.Image quality of 70 kV/65 mA group was reduced but could meet the requirements of diagnosis (image quality score >3),and the radiation dose of this group decreased by 81.33%.Conclusion Reconstructed with SAFRIE technology,the image quality of 100 kV/65 mA scanning of chest CT is similar to that of routinely reconstructed images in regular dose,while the image quality of 70 kV/65 mA scanning can not only meet the requirements of diagnosis but also obviously reduce radiation dose.

After the preparation of cationic liposomes composed of DDAB/DOPE, cationic liposome-DNA complexes and lipid-polycation-DNA (LPD) complexes were formulated, respectively. Gel retardation assay was employed to select appropriate ratios of cationic liposomes to DNA of the liposome-DNA complexes. The morphology of LPD and liposome-DNA complexes was observed by transmission electron microscopy. The diameter and surface charge of LPD and liposome-DNA complexes were measured by photon correlation spectroscopy (PCS). Their transfection efficiencies in Chang cells and HepG2 cells were evaluated by beta-gal assay kit. It was found that LPD and liposome-DNA complexes had a regular spherical surface. However, compared with liposome-DNA complexes, LPD had rather smaller particle size and much higher transfection efficiency in Chang cells and HepG2 cells in vitro. LPD could be prepared easily with small particle sizes and high transfection activities. LPD may be a good non-viral gene delivery vehicle for applications in gene delivery.
Cations ; DNA ; genetics ; Genetic Therapy ; Genetic Vectors ; Humans ; Lipids ; chemistry ; Liposomes ; chemistry ; Liver Neoplasms ; metabolism ; pathology ; Protamines ; chemistry ; Transfection ; Tumor Cells, Cultured

To explore the biological effects of shear stress on intact artery and the change of growth factor during stress-induced vascular remodeling, we established an artery organ-cultured system under stress in vitro, and the common carotid arteries of pigs were cultured under shear stress of 20, 5 and 0 dyn/cm2. PDGF-A synthesis of vascular smooth muscle cells (VSMCs) cultured for 1, 4 and 7 days were studied by immunohistochemical and computer image processing methods, and PDGF-B secretion of endothelial cells (ECs) cultured within 12 h were studied by ELISA. Results showed that PDGF-B increased obviously under shear stress of 5 dyn/cm2, and reached the highest point at about 3 h; PDGF-A synthesis also obviously increased under low shear stress in 7 days. Increasing of PDGF synthesis promotes phenotype switch and proliferation of VSMC. It may have important influence on artery remodeling under low shear stress.
Animals ; Carotid Artery, Common ; chemistry ; metabolism ; Cells, Cultured ; Endothelium, Vascular ; cytology ; metabolism ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Platelet-Derived Growth Factor ; biosynthesis ; Shear Strength ; Stress, Mechanical ; Swine