The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

OBJECTIVES: This study aimed to compare the effectiveness of ultrasound and acoustic and laser cleaning of curved root canals. METHODS: A total of 92 molars with independent root canals with a curvature of 20°-40° were prepared and standardized at 04 25# and stained with gentian violet solution for 72 h. Among them, 52 were randomly divi-ded into four groups for final rinsing (n=13): NI group, PUI group, EDDY group, and PIPS group. Ten samples in each group were cut horizontally along the long axis perpendicular to the root and divided into curved upper, curved, and apical segments. Images were taken with a stereomicroscope and Image J measurements were taken to calculate the depth of rinse penetration. The remaining three samples from each group were split along the long axis of the dentin, photographed by scanning electron microscope to record the dentin tubule exposure and staining layer, and scored for staining layer by double-blind method. SPSS 26.0 software was used to perform statistical analysis and select the best flushing method. An extra 40 samples were randomly divided into four groups for detection of flushing fluid penetration depth (n=10): 10, 20, 30, and 40 s. RESULTS: In the upper part, the mean depth of infiltration was not significantly different between the experimental and control groups (P>0.05). The PIPS group had a significantly lower smear layer score than the control group and the EDDY group (P<0.01). In the curved segment, the mean depth of infiltration was significantly greater in the PUI group than in the control group (P<0.05); the tarnish layer score was lower in each experimental group than in the control group. At the top, the mean depth of infiltration was greater in the PUI and PIPS groups than in the control group (P<0.05), and the smear layer score was lower in the PIPS group than in the other groups (P<0.05). After the time was changed, the depth of infiltration of PUI increased only in the apical segment as the flushing time increased. CONCLUSIONS The PUI and PIPS methods facilitate the penetration of irrigation solution into the dentin canal in curved root canals, especially in the apical segment. The PIPS technique is effective in removing the smear layer in curved root canals.
Humans ; Dental Pulp Cavity ; Microscopy, Electron, Scanning ; Root Canal Irrigants ; Root Canal Preparation/methods* ; Smear Layer ; Sodium Hypochlorite ; Therapeutic Irrigation/methods* ; Double-Blind Method

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: To explore the relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). Methods: This was an observational study based on data from a multicenter, prospective Chinese atrial fibrillation registry cohort, which included 18 703 consecutive patients with atrial fibrillation (AF) in 31 hospitals in Beijing from August 2011 to December 2018. Patients were divided into 5 groups according to status of comorbid diabetes and fasting glucose levels at admission: normal blood glucose (normal glucose group), pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group. Patients were followed up by telephone or outpatient service every 6 months. The primary follow-up endpoint was thromboembolic events, including ischemic stroke and systemic embolism. The secondary endpoint was the composite endpoint of cardiovascular death and thromboembolic events. Kaplan-Meier survival analysis and multifactorial Cox regression were used to analyze the correlation between fasting glucose levels and endpoint events. Results: The age of 18 703 patients with NVAF was (63.8±12.0) years, and there were 11 503 (61.5%) male patients. There were 11 877 patients (63.5%) in normal blood glucose group, 2 023 patients (10.8%)in pre-diabetes group, 1 131 patients (6.0%) in strict glycemic control group, 811 patients in average glycemic control group and 2 861 patients(4.3%) in poor glycemic control group. Of the 4 803 diabetic patients, 1 131 patients (23.5%) achieved strict glycemic control, of whom 328 (29.0%) were hypoglycemic (fasting blood glucose level<4.4 mmol/L at admission). During a mean follow-up of (51±23) months (up to 82 months), thromboembolic events were reported in 984 patients (5.3%). The survival curve analysis of Kaplan Meier showed that the incidence rates of thromboembolic events in normal glucose group, pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group were 1.10/100, 1.41/100, 2.09/100, 1.46/100 and 1.71/100 person-years, respectively (χ²=53.0, log-rank P<0.001). The incidence rates of composite endpoint events were 1.86/100, 2.17/100, 4.08/100, 2.58/100, 3.16/100 person-years (χ²=72.3, log-rank P<0.001). The incidence of thromboembolic events and composite endpoint events in the other four groups were higher than that in the normal blood glucose group (P<0.001). Multivariate Cox regression analysis showed that compared with normal glucose group, the risk of thromboembolism increased in pre-diabetes group(HR=1.23, 95%CI 1.00-1.51, P=0.049), strict glycemic control group(HR=1.32, 95%CI 1.06-1.65, P=0.013) and poor glycemic control group(HR=1.26, 95%CI 1.01-1.58, P=0.044). Conclusion: Both high or low fasting glucose may be an independent risk factor for thromboembolic events in patients with NVAF.
Aged ; Atrial Fibrillation/complications* ; Blood Glucose/analysis* ; Fasting ; Humans ; Male ; Middle Aged ; Prospective Studies ; Thromboembolism/etiology*

The morbidity and mortality of cardiovascular diseases are increasing annually, which is one of the primary causes of human death. Recent studies have shown that epoxyeicosatrienoic acids (EETs), endogenous metabolites of arachidonic acid (AA) via CYP450 epoxygenase, possess a spectrum of protective properties in cardiovascular system. EETs not only alleviate cardiac remodeling and injury in different pathological models, but also improve subsequent hemodynamic disturbances and cardiac dysfunction. Meanwhile, various studies have demonstrated that EETs, as endothelial-derived hyperpolarizing factors, regulate vascular tone by activating various ion channels on endothelium and smooth muscle, which in turn can lower blood pressure, improve coronary blood flow and regulate pulmonary artery pressure. In addition, EETs are protective in endothelium, including inhibiting inflammation and adhesion of endothelial cells, attenuating platelet aggregation, promoting fibrinolysis and revascularization. EETs can also prevent aortic remodeling, including attenuating atherosclerosis, adventitial remodeling, and aortic calcification. Therefore, it is clinically important to study the physiological and pathophysiological effects of EETs in the cardiovascular system to further elucidate the mechanisms, as well as provide new strategy for the prevention and treatment of cardiovascular diseases. This review summarizes the endogenous cardioprotective effects and mechanisms of EETs in order to provide a new insight for research in this field.
8,11,14-Eicosatrienoic Acid/pharmacology* ; Cardiovascular System ; Cytochrome P-450 Enzyme System ; Eicosanoids ; Endothelial Cells ; Humans

Abdomen ; Hernia ; Humans ; Prostheses and Implants ; Prosthesis Implantation ; Treatment Outcome

Objective:To study the influence of G protein-coupled estrogen receptor 1 (GPER1) specific agonist G1 and antagonist G2 in epilepsy susceptibility of temporal lobe epileptic rats.Methods:Sixty rats were randomly divided into control group, G1 treatment group and G15 treatment group ( n=20). Rats in the latter two groups were intraperitoneally injected with GPER1 agonist G1 (10 μg) or antagonist G15 (40 μg) for a consecutive 12 d. Lithium chloride pilocarpine epilepsy models were prepared in the 3 groups. The behavior manifestations of these rats were observed within 1 h of intraperitoneal injection of pilocarpine; Racine grading was used to evaluate the severity of epileptic seizures every 5 min; the latency of epileptic seizures (Racine grading IV) and epileptic seizure grading at different time points in the 3 groups were compared. The EEG monitoring was performed to these rats, and EEG data were recorded from 10 min before pilocarpine injection to 2 h after pilocarpine injection; EEG time-frequency was analyzed by Fast-Fourier transform (FFT); distribution of brain electrical energy and changes of θ and α wave energy during 20 min of epileptic status were compared among the 3 groups. Results:(1) As compared with that in the control group and G1 treatment group, the latency of epileptic seizures in the G15 treatment group was significantly shortened ( P<0.05); 15 and 20 min after pilocarpine injection, the epileptic seizure grading of rats in G1 treatment group was statistically lower than that in control group ( P<0.05); 15-35 min after pilocarpine injection, the epileptic seizure grading of rats in G15 treatment group was significantly higher than that in control group ( P<0.05). (2) As compared with those in the control group, rats in the G1 treatment group had smaller brain wave amplitude, while the rats in the G15 treatment group had earlier seizure time, larger brain wave amplitude and higher frequency. There were no obvious changes in the amount of brain electrical energy between the G1 treatment group and control group; while the amount of brain electrical energy in the G15 treatment group 2 h after pilocarpine injection was higher than that in the control group. As compared with those in the control group and G1 treatment group, the θ and α wave energy values of rats in the G15 treatment group were significantly increased within 20 min of epileptic status ( P<0.05). Conclusion:Activation level of GPER1 might be associated with susceptibility to epileptic seizures, and specific inhibition of GPER1 activation can enhance the susceptibility to epilepsy and increase the energy values of specific frequency bands during epilepsy.

Objective: To explore the feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture (ASP) during radiofrequency ablation for atrial fibrillation. Methods: We enrolled 241 consecutive patients scheduled to radiofrequency ablation for atrial fibrillation in Beijing Anzhen Hospital from July to September 2020. Inclusion criteria: patients aged over 18 years with a clear electrocardiogram record of atrial fibrillation. Patients were divided into 2 groups: ASP with ultrasound-assisted X-ray (ultrasound group, n=123), ASP under X-ray alone (X-ray group, n=118). Clinical features of patients including age, sex, percent of paroxysmal atrial fibrillation, and repeat ablation, CHA₂DS₂-VASc score and past history (hypertension, diabetes mellitus, coronary artery disease, stroke/transient ischemic attack (TIA), valve diseases) and echocardiographic parameters (left atrial dimension, left ventricular ejection fraction, left ventricular end-diastolic dimension) were obtained and compared. The first-pass rate, radiation exposure time, duration of ASP, and complications of ASP were also compared between the two groups. Results: The age of patients in this cohort was (62.5±8.0) years, and the proportion of males was 57.0% (n=138). Among them, the proportion of paroxysmal atrial fibrillation was 56.0% (n=135), and the ratio of repeat ablation was 17.8% (n=43). Age, sex, percent of paroxysmal atrial fibrillation, history of hypertension, diabetes mellitus were similar between the two groups. The first-pass rate was significantly higher in the ultrasound group than in the X-ray group (94.3% (116/123) vs. 79.7% (94/118), P=0.001); the exposure time of X-ray was significantly shorter in the ultrasound group than in the X-ray group ((31.3±7.9) s vs. (124.8±35.7) s, P<0.001), while the duration of ASP was longer in the ultrasound group ((10.1±1.8) minutes vs. (8.2±1.3) minutes, P<0.001). In terms of complications, the incidence of puncture into the pericardium was lower in the ultrasound group (0 vs.3.4% (4/118), P=0.039); the rate of transient ST-segment elevation post ASP was similar between the ultrasound group and X-ray group (2.4% (3/123) vs. 1.7% (2/118), P=0.999). Conclusion: Intracardiac ultrasound-assisted atrial septal puncture can effectively improve the accuracy of atrial septal puncture, shorten the radiation exposure time, and reduce the complications related to atrial septal puncture.
Adult ; Aged ; Atrial Fibrillation/surgery* ; Catheter Ablation ; Feasibility Studies ; Heart Septal Defects, Atrial ; Humans ; Male ; Middle Aged ; Punctures ; Radiofrequency Ablation ; Stroke Volume ; Ventricular Function, Left

OBJECTIVE: Our previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism. METHODS: We established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl's staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays. RESULTS: We found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats. CONCLUSION Taken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.

The safety of traditional Chinese medicine is affected by many factors, and the influence of exogenous harmful substances has been concerned and become a hot spot in recent years, especially heavy metals, pesticide residues and some other harmful substances. In order to explore the effects of non-soil and non-pesticide treatment on residues of these two harmful substances, the heavy metals and agricultural residues of Lilii Bulbus were detected, and the correlation of the data was analyzed. In this experiment, heavy metals and pesticide residues of Scrophulariae Radix were detected, and correlation analysis was conducted for their data. The mechanism of transport phase was interpreted with statistical moment similarity tool of total fingerprint by supramolecular chemistry theory. A large number of experimental data in this paper showed that heavy metals and pesticide contents in Lilii Bulbus basaltifolia had a positive correlation, which was closely related to supramolecular phenomena. Moreover, the similarity of fingerprints between Lilii Bulbus and Scrophulariae Radix suggested that Lilii Bulbus and Scrophulariae Radixa had a high selectivity in absorption of agricultural residues, which proved that the absorption of pesticides in Lilii Bulbus and Scrophulariae Radix from different habitats had the function of supramolecular imprinting template. It was considered that medicinal plant was a giant complex supramolecule with various levels of " imprinted template" . Heavy metals and agricultural residues were also involved in plant growth, forming an " imprinted template" for the formation of supramolecules between agricultural residues and heavy metals. After heavy metals and agricultural residues formed supramolecules, their liposolubility and permeability changed in varying degrees, and their transport in medicinal plants was promoted. Finally, the heavy metal supramolecules of pesticides were absorbed, distributed, aggregated and accumulated in plants. The purpose of the study was to reveal the mechanism of heavy metal and pesticide supramolecule transport, provide a new direction for the treatment of heavy metals and pesticide residues, and ensure the safety of traditional Chinese medicine.