ABSTRACT
Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Exosomes , Ferroptosis , Head and Neck Neoplasms , Macrophages , Squamous Cell Carcinoma of Head and NeckABSTRACT
<p><b>OBJECTIVE</b>To explore the risk factors of nosocomial infection in severe craniocerebral trauma and the way of prevention.</p><p><b>METHODS</b>The clinical data of 387 patients with severe craniocerebral trauma were reviewed.</p><p><b>RESULTS</b>The total nosocomial infection rate of this study was 22.99%. Pulmonary nosocomial infection presented most frequently. The G-bacilli were the most common infectious bacteria. The mortality rate of the infection group was 38.20%.</p><p><b>CONCLUSIONS</b>Complications of nosocomial infection affect the prognosis of craniocerebral trauma patients. Nosocomial infection is related to the age of the patients, craniocerebral trauma severity, unreasonable utilization of antibiotics and invasive operations, such as tracheal cannula, mechanical ventilation, urethral catheterization and deep venous catheterization. Patients with severe craniocerebral trauma should be carefully treated and nursed to avoid nosocomial infection. In order to reduce the rate of nosocomial infection, intensive measurement should be adopted.</p>