Astragaloside IV Reduces Lung Epithelial Cell Pyroptosis via TXNIP-NLRP3-GSDMD pathway.

This study aimed to investigate the detrimental impact of cigarettes on lung cells and the potential effects of astragaloside IV on lung epithelial cell oxidative stress and pyroptosis. The research utilized cigarette smoke extract (CSE) to stimulate lung epithelial cells BEAS-2B, assessed cytotoxicity using the CCK-8 method, and measured changes in reactive oxygen species (ROS) and mitochondrial membrane potential with a probe method. Additionally, Seahorse XF24 was employed to analyze the impact of CSE on mitochondria in lung epithelial cells. Furthermore, LPS and cigarette combination-treated mice were created, alveolar damage was evaluated using HE staining, and changes in the key protein GSDMD of pyroptosis were detected using western blot (WB). The study also utilized the CCK-8 method to assess the potential toxic effects of astragaloside IV on lung epithelial cells, and the probe method to monitor changes in ROS and mitochondrial membrane potential. WB analysis was conducted to observe protein alterations in the TXNIP/NLRP3/GSDMD pathway. CSE concentration-dependently reduced cell activity, increased cellular ROS levels, and decreased mitochondrial membrane potential. CSE also decreases basal respiratory capacity, respiratory reserve capacity, and ATP production levels in cells. In LPS and cigarette combination-treated mice, cigarette smoke caused the alveolar septum to break and alveoli to enlarge, while increasing the expression of pyroptosis-related protein GSDMD. Astragaloside IV did not show significant cytotoxic effects within 48 h of treatment and could reduce CSE-induced ROS levels while increasing mitochondrial membrane potential. WB results indicated that astragaloside IV reduced the activation of the TXNIP/NLRP3/GSDMD signaling pathway in lung epithelial cells exposed to CSE. Our study demonstrates that CSE induces oxidative stress and impairs mitochondrial function in pulmonary epithelial cells, while astragaloside IV can potentially reverse these effects by inhibiting the TXNIP-NLRP3-GSDMD signaling pathway, thereby mitigating CSE-induced pulmonary disease and epithelial cell pyroptosis.

Experimental validation of an advanced impedance pneumography for monitoring ventilation volume during programmed cycling exercise.

Objective.Impedance pneumography (IP) has provided static assessments of subjects' breathing patterns in previous studies. Evaluating the feasibility and limitation of ambulatory IP based respiratory monitoring needs further investigation on clinically relevant exercise designs. The aim of this study was to evaluate the capacity of an advanced IP in ambulatory respiratory monitoring, and its predictive value in independent ventilatory capacity quantification during cardiopulmonary exercise testing (CPET).Approach.35 volunteers were examined with the same calibration methodology and CPET exercise protocol comprising phases of rest, unloaded, incremental load, maximum load, recovery and further-recovery. In 3 or 4 deep breaths of calibration stage, thoracic impedance and criterion spirometric volume were simultaneously recorded to produce phase-specific prior calibration coefficients (CCs). The IP measurement during exercise protocol was converted by prior CCs to volume estimation curve and thus calculate minute ventilation (VE) independent from the spirometry approach.Main results.Across all measurements, the relative error of IP-derived VE (VER) and flowrate-derived VE (VEf) was less than 13.8%. In Bland-Altman plots, the aggregate VE estimation bias was statistically insignificant for all 3 phases with pedaling exercise and the discrepancy between VERand VEffell within the 95% limits of agreement (95% LoA) for 34 or all subjects in each of all CPET phases.Significance.This work reinforces the independent use of IP as an accurate and robust alternative to flowmeter for applications in cycle ergometry CPET, which could significantly encourage the clinical use of IP and improve the convenience and comfort of CPET.

Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia.

PURPOSE: As a public health emergency of international concern, coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia. MATERIALS AND METHODS: 62 patients were randomly assigned to a treatment group (LIPUS treatment area - Group 1; self-control area - Group 2) and an external control group (Group 3). The primary outcomes were the volume absorption rate (VAR) and the area absorption rate (AAR) of lung inflammation in CT images. RESULTS: After an average duration of treatment 7.2 days, there were significant differences in AAR and VAR between Group 1 and Group 2 (AAR 0.25 vs 0.12, p=0.013; VAR 0.35 vs 0.11, p=0.005), and between Group 1 and Group 3 (AAR 0.25 vs 0.11, p=0.047; VAR 0.35 vs 0.19, p=0.042). Neither AAR nor VAR was statistically different between Group 2 and Group 3. After treatment, C-reactive protein, interleukin-6, leukocyte, and fingertip arterial oxygen saturation (SaO2) improved in Group 1, while in Group 3 only fingertip SaO2 increased. CONCLUSION: LIPUS therapy reduced lung inflammation and serum inflammatory factor levels in hospitalized COVID-19 patients, which might be a major advancement in COVID-19 pneumonia therapy.

Risk Prediction for Arrhythmias by Heart Rate Deceleration Runs in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is associated with increased incidence of arrhythmias, which has been attributed to autonomic dysregulation. Detection of autonomic function may facilitate stratification of COPD patients with respect to their risk of development of arrhythmias. Patients and Methods: A total of 151 COPD patients and 45 non-COPD patients were included in this study. Heart rate deceleration runs (DRs) were detected by dynamic electrocardiogram (ECG); DRs successively occurring in 2, 4, or 8 cardiac cycles were denoted as DR2, DR4, and DR8, respectively. Indicators of arrhythmias including isolated premature atrial contractions (PAC), supraventricular tachycardia (SVT), isolated premature ventricular contractions (PVC), and ventricular tachycardia (VT) were recorded. Occurrence of SVT or PAC ≥70/day was considered positive for supraventricular arrhythmias, while positive ventricular arrhythmias category (PVAC) was defined as occurrence of VT or PVC ≥10/hour. Results: Compared with non-COPD individuals, COPD patients were associated with increased number of PAC, PVC, higher incidence of PAC >70/d, SVT, PVAC, and decreased DRs (DR2, DR4, DR8) (P<0.05). In COPD patients, DRs showed a negative correlation with the incidence of PAC, PVC, SVT, and PVAC (P<0.05). In receiver operating characteristic curve analysis, all the DRs were found to be significant predictors of PAC >70/d, SVT, and PVAC. The predictive power of DRs was significantly different from one another with the order ranged as DR4>DR8>DR2 for PAC >70/d, DR8>DR4>DR2 for SVT, and DR8>DR4>DR2 for PVAC. Conclusion: Our study provides evidence of significant autonomic dysregulation in COPD patients. DRs may serve as a marker of the risk of arrhythmias in COPD patients.

Cardiac autonomic function in patients with acute exacerbation of chronic obstructive pulmonary disease with and without ventricular tachycardia.

BACKGROUND: Autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD) may increase the risks of arrhythmia and sudden death. We studied cardiac autonomic function in patients with acute exacerbation of COPD (AECOPD). METHODS: Patients with AECOPD were classified into ventricular tachycardia (VT) and non-VT groups according to the presence or absence of VT. The following parameters derived from 24-h Holter monitoring were compared between groups: average heart rate, heart rate deceleration capacity (DC), heart rate acceleration capacity (AC), standard deviation of normal RR intervals (SDNN), standard deviation of average RR interval in 5-min segments (SDANN), root mean square of standard deviations of differences between adjacent normal RR intervals (rMSSD), low-frequency power (LF), high-frequency power (HF) and LF/HF ratio. RESULTS: Seventy patients were included, 22 in the VT group and 48 in the non-VT group. The groups had similar clinical characteristics (except for more common amiodarone use in the VT group, P < 0.05) and general ECG characteristics. DC, SDNN, SDANN and rMSSD were lower and AC higher in the VT group (P < 0.05). In the VT group, DC was correlated positively with SDNN (r = 0.716), SDANN (r = 0.595), rMSSD (r = 0.571) and HF (r = 0.486), and negatively with LF (r = -0.518) and LF/HF (r = -0.458) (P < 0.05). AC was correlated negatively with SDNN (r = -0.682), SDANN (r = -0.567) and rMSSD (r = -0.548) (P < 0.05). CONCLUSIONS: DC decreased and AC increased in patients with AECOPD and VT, reflecting an imbalance in autonomic regulation of the heart that might increase the risk of sudden death.