The induction of ferroptosis by KLF11/NCOA4 axis: the inhibitory role in clear cell renal cell carcinoma.

Ferroptosis is a form of cell death and has great potential application in the treatment of many cancers, including clear cell renal cell carcinoma (ccRCC). Herein, we identified the essential roles of Krüppel-like factor 11 (KLF11) in suppressing the progression of ccRCC. By analyzing mRNA expression data from the Gene Expression Omnibus (GEO) database, we found that KLF11 was a significantly downregulated gene in ccRCC tissues. The results of subsequent functional assays verified that KLF11 played an antiproliferative role in ccRCC cells and xenograft tumors. Furthermore, gene set enrichment analysis indicated that ferroptosis was involved in ccRCC development, and correlation analysis revealed that KLF11 was positively related to ferroptosis drivers. We also found that KLF11 promoted ferroptosis in ccRCC by downregulating the protein expression of ferritin, system xc (-) cystine/glutamate antiporter (xCT), and glutathione peroxidase 4 (GPX4), acting as the inhibitory factors of ferroptosis and increasing the intracellular levels of lipid reactive oxygen species (ROS). As a transcriptional regulator, KLF11 significantly increased the promoter activity of nuclear receptor coactivator 4 (NCOA4), a gene significantly downregulated in ccRCC and whose low expression is associated with poor survival. The characteristics of ccRCC cells caused by KLF11 overexpression were reversed after NCOA4 silencing. In summary, the present study suggests that KLF11 suppresses the progression of ccRCC by increasing NCOA4 transcription. Therefore, the KLF11/NCOA4 axis may serve as a novel therapeutic target for human ccRCC.

Influence of exhalation valve and nebulizer position on albuterol delivery during noninvasive positive pressure ventilation.

BACKGROUND: Early studies have found better clinical efficiency when a nebulizer was used with noninvasive positive pressure ventilation (NPPV), compared with spontaneous breathing without NPPV. However, very limited research addressed factors that might affect aerosol delivery. This study aimed to investigate the influence of exhalation valves and nebulizer positions on aerosol delivery during NPPV. METHODS: We determined the efficiency of aerosol delivery in patients receiving NPPV with a lung model that simulates spontaneous breathing. Single-arch exhalation port, plateau exhalation valve, and whisper swivel were chosen as exhalation valves under different levels of inspiratory and expiratory pressures. A nebulizer was filled with 1 mL of 0.5% albuterol solution in 3 mL of normal saline, driven with 8 L/min oxygen, and placed at either a proximal position in the ventilator circuit (near the ventilator outlet, where humidifiers are usually connected) or a distal position in the ventilator circuit (between exhalation valve and lung model connection). Albuterol was collected by filters and then measured by ultraviolet spectrophotometry. The velocities of gas flow were also measured at different nebulizer positions. RESULTS: Significant differences in the gas flow velocity were shown between proximal and distal positions of the breathing circuit under four combinations of inspiratory and expiratory pressure levels (15/5, 15/10, 25/5, and 25/10 cmH2O) (p<0.05). When the nebulizer was positioned distally, the single-arch exhalation port had the highest aerosol delivery, and the whisper swivel had the lowest aerosol delivery (p<0.05). When the nebulizer was placed proximally, the single-arch exhalation port had lower efficiency of aerosol delivery than the whisper swivel and plateau exhalation valve (p<0.05). In addition, higher inspiratory pressure was associated with increased aerosol delivery (p<0.05). The influence of expiratory pressure on aerosol delivery appeared too complex to predict. CONCLUSIONS: The type of exhalation valve and the position of the nebulizer in the ventilator circuit have a significant influence on the efficiency of aerosol delivery during NPPV. As a result, with different exhalation valves, an appropriate nebulizer position should be carefully chosen, and the inhaled dose should be adjusted after accurate prediction of aerosol delivery to ensure optimal clinical efficacy.

[The comparative analysis of the common reasons of invasive ventilator alarms between medical and specialist intensive care unit].

OBJECTIVE: To analyze the common reasons of invasive ventilator alarms between medical intensive care unit (ICU) and specialist ICU, and its related management methods. METHODS: Patients admitted to medical ICU and specialist ICU from January to December in 2011 of the First Hospital of China Medical University were studied. Ventilator alarms and their reasons need to be handle by the front-line doctors, respiratory therapists, attending physicians or medical ICU doctors were analyzed and compared. RESULTS: There were 375 ventilator alarms of the 59 patients in the medical ICU, incidence of the top three alarms parameters were high airway pressure alarms for 21.87%, high tide volume alarms for 15.73% and high minute ventilation alarms for 14.13%. In specialist ICU there were a total of 403 ventilator alarms with 249 patients, incidence of the top three alarms parameters were high airway pressure alarms for 32.51%, low airway pressure alarms for 15.38%, high respiratory rate alarms for 10.42%. The incidence of high airway pressure and low airway pressure alarms in medical ICU were significantly lower than the specialist ICU (21.87% vs. 32.51%, 8.53% vs. 15.38%, both P<0.01), and the incidence of high minute ventilation and high tidal volume alarms in medical ICU were higher than specialist ICU (14.13% vs. 7.20%, 15.73% vs. 9.68%, P<0.01 and P<0.05). The top three causes of the alarms were aerosol inhalation, sputum blockage, and oxygen battery expired in medical ICU, and sputum blockage, respiratory distress, and pipeline leak and oxygen expired battery in specialist ICU. The reasons of sputum blockage, tubes factors (intubation position change, pipeline water) and improper alarm parameters setting in medical ICU was significantly lower than those in specialist ICU (10.93% vs. 17.12%, 1.87% vs. 4.47%, 1.33% vs. 3.72%, 1.60% vs. 3.97%, all P<0.05). High tidal volume, high minute ventilation and serious breath-side filter blockage because of aerosol inhalation in medical ICU were significantly higher than those in specialist ICU (18.93% vs. 3.97%, P<0.01). CONCLUSION: Doctors in medical ICU and specialist ICU should understand the ventilator alarms characteristics, prevention, detect and timely problems management.