[Design and application of alaryngeal mask and monitoring device facilitating withdrawal of endotracheal tube].

Percutaneous dilatational tracheostomy (PDT) is a surgical method for quickly establishing an artificial airway, which has been favored by clinicians because of its simple operation, small trauma and bedside operation. However, for patients with tracheal intubation in intensive care unit (ICU), the tip and balloon of the existing endotracheal tube will not only hinder percutaneous puncture, but also hinder insertion of guidewire and tracheotomy tube, and consequently affect the process of PDT. On the contrary, blind withdrawal of the existing endotracheal tube may cause the tracheal tube tipleave the glottis, leading to an emergency airway situation that endangers the patient's life. Therefore, the medical staff from intensive care medicine department of the First People's Hospital of Chenzhou designed a laryngeal mask and its monitoring device, which is convenient for withdrawal of endotracheal tube, and obtained the national utility model patent of China (patent number: ZL 2020 2 2795887.1). The device is composed of a laryngeal mask and a monitoring device. The laryngeal mask mainly includes a laryngeal mask body, a vent tube, a guidance tube and other components. The laryngeal mask body is mainly used to seal the throat and provide the air supply channel for the patient together with the ventilation tube. The main function of the guidance tube is to accommodate the tracheal tube and facilitate the withdrawal of the inserted tracheal tube. During percutaneous dilatation tracheotomy, this device can monitor the withdrawal of tracheal catheter in real time, and immediately ensure the airway patency of patients without re-intubation when the cuff of tracheal catheter exits the glottis. The utility model has the advantages of real-time monitoring, simple operation, safety and convenience, and is worthy of transformation and promotion.

SIRTUIN 5 ALLEVIATES EXCESSIVE MITOCHONDRIAL FISSION VIA DESUCCINYLATION OF ATPASE INHIBITORY FACTOR 1 IN SEPSIS-INDUCED ACUTE KIDNEY INJURY.

ABSTRACT: Sepsis-induced acute kidney injury (SAKI) poses a significant clinical challenge with high morbidity and mortality. Excessive mitochondrial fission has been identified as the central pathogenesis of sepsis-associated organ damage, which is also implicated in the early stages of SAKI. Sirtuin 5 (SIRT5) has emerged as a central regulator of cellular mitochondrial function; however, its role in the regulation of sepsis-induced excessive mitochondrial fission in kidney and the underlying mechanism remains unclear. In this study, SAKI was modeled in mice through cecal ligation and puncture, and in human renal tubular epithelial (HK-2) cells stimulated with lipopolysaccharide (LPS), to mimic the cell SAKI model. Our findings revealed that septic mice with a SIRT5 knockout exhibited shortened survival times and elevated levels of renal injury compared to wild-type mice, suggesting the significant involvement of SIRT5 in SAKI pathophysiology. Additionally, we observed that SIRT5 depletion led to increased renal mitochondrial fission, while the use of a mitochondrial fission inhibitor (Mdivi-1) reversed the detrimental effects caused by SIRT5 depletion, emphasizing the pivotal role of SIRT5 in preventing excessive mitochondrial fission. In vitro experiments demonstrated that the overexpression of SIRT5 effectively mitigated the adverse effects of LPS on HK-2 cells viability and mitochondrial fission. Conversely, downregulation of SIRT5 decreased HK-2 cells viability and exacerbated LPS-induced mitochondrial fission. Mechanistically, the protective function of SIRT5 may be in part, ascribed to its desuccinylating action on ATPase inhibitory factor 1. In conclusion, this study provides novel insights into the underlying mechanisms of SAKI, suggesting the possibility of identifying future drug targets in terms of improved mitochondrial dynamics by SIRT5.

Inhibition of CISD1 alleviates mitochondrial dysfunction and ferroptosis in mice with acute lung injury.

The NET family member, CDGSH iron-sulfur domain-containing protein 1 (CISD1), is located in theoutermembrane of mitochondria, where it regulates energy and iron metabolism. CISD1 has vital functions in certain human diseases; however, its function in acute lung injury (ALI) is unknown. ALI pathogenesis critically involves mitochondrial dysfunction and ferroptosis, which might be regulated by CISD1. Therefore, we investigated CISD1's function in mitochondrial dysfunction and ferroptosis regulation in lipopolysaccharide (LPS)-induced ALI. We found that CISD1 was upregulated in LPS-induced ALI,and silencing Cisd1 prevented cell apoptosis and increased cell viability. When CISD1was inhibited by mitoNEET ligand-1 (NL-1) there was a significant mitigation of pathological injury and lung edema, and reduced numbers of total cells, polymorphonuclear leukocytes, and a decreased protein content in the bronchoalveolar lavage fluid (BALF). Moreover, inhibition of CISD1 markedly decreased the interleukin (IL)6, IL-1ß, and tumor necrosis factor alpha (TNF-α) levels in the lungs and BALF of ALI-model mice. Silencing of Cisd1 prevented LPS-induced mitochondrial membrane potential depolarization, cellular ATP reduction, and reactive oxygen species (ROS) accumulation, suggesting mitochondrial protection. ALI activated ferroptosis, as evidenced by the increased lipid-ROS, intracellular Fe2+ level, reduced Gpx4 (glutathione peroxidase 4) expression, and the glutathione/glutathione disulfide ratio. Interestingly, inhibition of CISD1 reduced LPS-induced ferroptosis in vivo and in vitro. In conclusion, inhibition of CISD1 alleviated mitochondrial dysfunction and ferroptosis in LPS-induced ALI, identifying CISD1 as possible target for therapy of LPS-induced ALI.

Inhibition of SIRT6 aggravates p53-mediated ferroptosis in acute lung injury in mice.

Although studies have shown that protein 53 (p53)-mediated ferroptosis is involved in acute lung injury (ALI), the mechanism of its regulation remains unclear. The protective effects of Sirtuin 6 (SIRT6), a histone deacetylase, have been demonstrated in multiple diseases; however, further studies are needed to elucidate the role of SIRT6 in ALI. In the present study, we hypothesize that SIRT6 protects against lipopolysaccharide (LPS)-induced ALI by regulating p53-mediated ferroptosis. We observed that the inhibition of ferroptosis prevented LPS-induced ALI. The knockout of p53 blocked LPS-induced ferroptosis and ALI, suggesting that p53 facilitated ALI by promoting ferroptosis. In addition, the inhibition of SIRT6 aggravated LPS-induced ferroptosis and ALI, while the depression of ferroptosis blocked the exacerbation of lung injury induced by SIRT6 inhibition. The results suggest that SIRT6 protects against ALI by regulating ferroptosis. Furthermore, the inhibition of SIRT6 reinforced the p53 acetylation and the deletion of p53 rescued the exacerbation of ferroptosis induced by SIRT6 inhibition. The findings indicate that SIRT6 regulates the acetylation of p53 and prevents p53-mediated ferroptosis. In conclusion, our results indicate that SIRT6 protects against LPS-induced ALI by regulating p53-mediated ferroptosis, thereby demonstrating that SIRT6 holds great promise as a therapeutic target for ALI.

Low plasma leptin level at admission predicts delirium in critically ill patients: A prospective cohort study.

The pathophysiology of delirium remains poorly understood. Low leptin level has been associated with features leading to delirium such as dysregulated immune functions and loss of neuroprotective effects. The purpose of the present study was to investigate the relationship between plasma leptin level at intensive care unit (ICU) entry and subsequent occurrence of delirium in critically ill patients. This single-center prospective cohort study in China allocated 336 critically ill patients admitted to ICU between 05/2015 and 05/2016 into a delirium group (n=102) and non-delirium group (n=234) based on whether delirium occurred during their stay at the ICU. Patients were examined at least twice daily and delirium was diagnosed using the Confusion Assessment Method for the ICU (CAM-ICU). Blood samples were obtained after ICU entry. Plasma leptin concentrations were measured by ELISA. Delirium occurred in 30.4% (102/336) of patients. Patients who developed delirium showed significantly lower leptin level at ICU entry than those who did not (6.1±3.2 vs. 9.2±5.9ng/mL; P<0.001). Low plasma leptin level at ICU entry was independently associated with subsequent occurrence of delirium (OR, 0.865; 95%CI, 0.802-0.934; P<0.001). Other independent risk factors for delirium included increasing age (OR, 1.050; 95%CI, 1.020-1.080; P=0.001) and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score (OR, 1.148; 95%CI, 1.092-1.208; P<0.001). Patients who developed delirium had a prolonged duration of ICU stay and higher mortality. Low plasma leptin level at ICU entry was associated with the occurrence of delirium in critically ill patients.