Background: Nicotine (Nic), the major component of tobacco products, can induce apoptosis in lung epithelial cells, and the resulting damage contributes to chronic obstructive pulmonary disease. Apoptosis is closely related to autophagy. Resveratrol (Res) can induce autophagy and inhibit apoptosis. Therefore, the present study investigated whether Nic induces apoptosis of lung epithelial cells by regulating autophagy and the effect of Res on apoptosis of Nic-exposed lung epithelial cells. Methods: The BEAS-2B lung epithelial cell line was used to study the harmful effects of Nic and the potential benefits of Res as well as the underlying mechanisms. Viability and apoptosis were examined using the Cell Counting Kit-8 and annexin V-propidium iodide staining, respectively. The expression of levels of apoptosis-related proteins, autophagy-related proteins, and members of the PI3K/Akt/mTOR pathway was measured by western blotting. Autophagic flux was detected via mRFP-GFP-LC3 double-labeled adenovirus transfection and transmission electron microscopy. Results: Nic significantly reduce the viability and increased the apoptosis of BEAS-2B cells in a concentration-dependent manner. Nic treatment also increased the numbers of autophagosomes in BEAS-2B cells and upregulated LC3II and p62 expression. Moreover, Res at concentration of 2, 10, and 50 μM protected BEAS-2B cells from Nic apoptosis, and the expression of LC3II increased further and p62 decreased in Res pretreatment group. Apart from this, Res reduced Akt and mTOR phosphorylation. Subsequently, upon inhibiting PI3K phosphorylation by PI3K inhibitors, BEAS-2B cell autophagy induced by Res was obviously abolished. Conclusions: Nic-induced BEAS-2B cell apoptosis by inhibiting the late-stage autophagic flux, but Res could protect BEAS-2B cells from the detrimental effects of nicotine by enhancing autophagy via the PI3K/Akt/mTOR pathway. These results will provide an experimental basis for the prevention and treatment of COPD.
Background: High flow nasal oxygen (HFNO) therapy is a leading treatment technique for acute hypoxemic respiratory failure (AHRF), but its treatment failure rate remains high. The awake prone position(APP) has been proven to inease oxygenation and reduce the endotracheal intubation rate in patients with COVID-19-induced AHRF. However, because the APP is poorly tolerated in patients, its performance in improving prognoses is controversial. The lateral position has a similar mechanism and effect to the prone position, but it is more tolerable than the prone position. Thus, it is worth exploring whether the lateral position is better for awake patients with acute respiratory failure.
Methods: This is a protocol for a three-arm parallel group multicentre randomised controlled open-label exploratory trial. A total of 220 patients from two teaching hospitals in Chongqing, China, will be randomised to take the semirecumbent position, lateral position, or prone position at a ratio of 1:1:1. Patients are all diagnosed with AHRF secondary to non-COVID-19-related pneumonia or lung infection and receiving HFNO therapy. The primary outcome is 28-day all-cause mortality. The secondary outcomes are the 28-day intubation rate, total position change time, the incidence of adverse events, number of days using HFNO therapy, length of hospital and intensive care unit (ICU) stay, and others. We will conduct subgroup analyses on the arterial partial pressure of oxygen to the fraction of inspiration oxygen(PaO2/FiO2)ratio (>200 mmHg or ≤200 mmHg), time from hospitalisation to implementation (<24 h or ≥24 h), position changing time, and different diagnoses.
Discussion: Thistrial will explore the prognostic effects of the APP with that of the lateral position in awake patients with non-COVID-19 induced AHRF, and compare the differences between them. To provide evidence for clinical decision-making and further research on position management.
Trial registration: This trial was registered in the Chinese Clinical Trial Registry. The registration number is ChiCTR2200055822. Registered on January 20, 2022 ,https://www.chictr.org.cn/showproj.aspx?proj=130563
To explore the effects of establishing a high dependency unit (HDU) on the prognosis, outcome, and expenditure of patients with severe community-acquired pneumonia (SCAP). 108 SCAP patients were recruited from the respiratory intensive care unit (RICU) of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Of these, 87 qualified the study-selection criteria and were divided into HDU group (treated in HDU after discharge from RICU prior to transfer to normal unit) (n = 40) and normal group (not treated in the HDU) (n = 47). In the 87 patients, 40 were divided into HDU group, which meant they transferring to HDU when got stable while another 47 were divided into normal group which meant they staying longer in RICU and transferring to normal unit when got stable. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, duration of mechanical ventilation, hospital infection, intensive care unit syndrome, length of stay, and expenditure were compared between the two groups. The primary outcome was discharging from hospital while the secondary outcome was length of stay. There was no significant difference with respect to noninvasive ventilation time, oxygenation index, or APACHE II and SOFA scores at admission or discharge from RICU (P > 0.05). The mean invasive ventilation time (176 ± 160 h) of the HDU group was not significantly different from that in the normal group (206 ± 179 h). The period of sequential noninvasive ventilation in the HDU group (135 ± 82 h) was significantly shorter than that in the normal group (274 ± 182 h, P < 0.05). The HDU group had a shorter length of stay in hospital and RICU, and incurred lesser expenditure than patients in the normal group (P < 0.05). Patients in HDU group had almost the same therapeutic effect with shorter length of stay in hospital and RICU, and lesser expenditure.
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