Mitochondria protective and anti-apoptotic effects of peripheral benzodiazepine receptor and its ligands on the treatment of asthma in vitro and vivo.

BACKGROUND: Asthma is a prevalent respiratory inflammatory disease. Abnormal apoptosis of bronchial epithelial cells is one of the major factors in the progression of asthma. Peripheral benzodiazepine receptors are highly expressed in bronchial epithelial cells, which act as a component of the mitochondrial permeability transition pore to regulate its opening and closing and apoptosis of bronchial epithelial cells. We aimed to investigate the mechanisms by which peripheral benzodiazepine receptor and its ligands, agonist 4'-Chlorodiazepam (Ro5-4864) and antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11,195), modulate the mitochondrial function and cell apoptosis in the treatment of asthma. METHODS: In vitro study, Ro5-4864 and PK 11,195 were utilized to pretreat cells prior to the inflammatory injury induced by Lipopolysaccharide. The reactive oxygen species, the apoptosis of cell, the mitochondrial membrane potentials, the ultrastructures of the mitochondria and the expression levels of peripheral benzodiazepine receptors and apoptosis-related proteins and genes were detected. In vivo study, mice were administrated intraperitoneally with Ro5-4864 and PK 11,195 before sensitized and challenged by ovalbumin. Serum IgE and bronchoalveolar lavage fluid cytokines were detected, and lung tissues were underwent the histopathological examination. RESULTS: The ligands of peripheral benzodiazepine receptor counteracted the effects of the increase of reactive oxygen species, the elevated extent of apoptosis, the decrease of mitochondrial membrane potentials and the disruption of mitochondrial ultrastructures induced by Lipopolysaccharide. The ligands also promoted the expression of anti-apoptosis-related proteins and genes and inhibited the expression of pro-apoptosis-related proteins and genes. Besides, the ligands reduced the levels of serum IgE and bronchoalveolar lavage fluid cytokines in asthmatic mice and attenuated the histopathological damage of lungs. CONCLUSION: Peripheral benzodiazepine receptor serves as a potential therapeutic target for the treatment of asthma, with its ligands exerting mitochondrial protective and anti-apoptotic effects on bronchial epithelial cells.

Impact of airway devices and emergency airway techniques characteristics on airway adverse events in mainland China: a cross-sectional study.

BACKGROUND: Novel airway devices are becoming widely available, yet it is unclear whether the techniques or preferences of airway practitioners for airway management have been impacted. Given these facts, a cross-sectional study of the current status of airway management in mainland China was conducted and compared with previous survey findings. METHODS: The national survey was conducted from November 7th to November 28th, 2022. An electronic survey was sent to the New Youth Anesthesia Forum to examine the availability of airway devices, preference for front-of-neck access (FONA) techniques, the incidence of adverse airway events, and the status of airway management training. RESULTS: Questionnaires were completed by 3783 respondents, with a response rate of 72.14%. So far, the availability of optical airway devices has improved dramatically, with the availability of videolaryngoscopes reaching 97.18%. When encountering "cannot intubate, cannot ventilate" (CICV) scenarios, the majority of respondents would prefer needle cricothyrotomy to establish FONA. However, less than a quarter of respondents had actually performed it. Moreover, the incidence of airway adverse events from 2016 to 2022 was 11.48%, of which 5.13% were brain damage or death. Multivariate logistic regression analysis revealed that the ability to perform FONA techniques (odds ratio [OR] 0.23, 95% CI: 0.16, 0.32; P<0.001) and the availability of difficult airway management carts or kits (OR 0.59, 95% CI 0.41, 0.85; P=0.005) were associated with a lower incidence of airway adverse events. CONCLUSIONS: Optical airway devices can overcome some of the challenges posed by difficult airways, yet the CICV scenario remains a major obstacle. The future focus of airway management should be training, particularly for complicated emergency airway techniques.

National survey on the current status of airway management in China.

Apparently, understanding airway management status may help to reduce risk and improve clinical practice. Given these facts, our team conducted a second survey on the current status of airway management for mainland China following our 2016 national airway survey. The national survey was conducted from November 7 to November 28, 2022. An electronic survey was sent to the New Youth Anesthesia Forum, where Chinese anesthesiologists completed the questionnaire via WeChat. A total of 3783 respondents completed the survey, with a response rate of 72.14%. So far, in 2022, 34.84% of anesthesiologists canceled or delayed surgery at least once due to difficult airway. For the anticipated difficult airway management, 66.11% of physicians would choose awake intubation under sedation and topical anesthesia, while the percentage seeking help has decreased compared to the 2016 survey. When encountering an emergency, 74.20% of respondents prefer to use the needle cricothyrotomy, albeit less than a quarter have actually performed it. Anesthesiologists with difficult airway training experience reached 72.96%, with a significant difference in participation between participants in Tier 3 hospitals and those in other levels of hospitals (P < 0.001). The videolaryngoscope, laryngeal mask, and flexible intubation scope were equipped at 97.18%, 95.96%, and 62.89%, respectively. Additionally, the percentage of brain damage or death caused by difficult airways was significantly decreased. The study may be the best reference for understanding the current status of airway management in China, revealing the current advancements and deficiencies. The future focus of airway management remains on training and education.