ABSTRACT
BACKGROUND: Dexmedetomidine and propofol are two sedatives used for long-term sedation. It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation. AIM: To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury. METHODS: Patients who underwent mechanical ventilation for > 72 h were randomly assigned to receive sedation with dexmedetomidine or propofol. The Richmond Agitation and Sedation Scale (RASS) was used to evaluate sedation effects, with a target range of -3 to 0. The primary outcomes were serum levels of S100-ß and neuron-specific enolase (NSE) every 24 h. The secondary outcomes were remifentanil dosage, the proportion of patients requiring rescue sedation, and the time and frequency of RASS scores within the target range. RESULTS: A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group, respectively. Baseline data were comparable between groups. No significant differences were identified between groups within the median duration of study drug infusion [52.0 (IQR: 36.0-73.5) h vs 53.0 (IQR: 37.0-72.0) h, P = 0.958], the median dose of remifentanil [4.5 (IQR: 4.0-5.0) µg/kg/h vs 4.6 (IQR: 4.0-5.0) µg/kg/h, P = 0.395], the median percentage of time in the target RASS range without rescue sedation [85.6% (IQR: 65.8%-96.6%) vs 86.7% (IQR: 72.3%-95.3), P = 0.592], and the median frequency within the target RASS range without rescue sedation [72.2% (60.8%-91.7%) vs 73.3% (60.0%-100.0%), P = 0.880]. The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance (69.2% vs 50.8%, P = 0.045). Serum S100-ß and NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation, respectively (all P < 0.05). CONCLUSION: Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.
ABSTRACT
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder, and there are currently no effective drugs to delay progression of the disease. Ferroptosis may play a vital part in AD, and is therefore receiving increasing attention by researchers. AIM: To investigate the effects of dexmedetomidine (Dex) on ferroptosis in AD mouse hippocampus. METHODS: Hippocampal neurons (HNs) HT22 were induced by amyloid ß-protein (Aß) and both in vitro and in vivo AD mouse models were prepared via injections. The cell-counting kit-8 assay and immunofluorescence technique were adopted to determine cell proliferation activity and intracellular Fe2+ levels, and the TBA method and microplate method were employed for malondialdehyde and glutathione measurements, respectively. Hippocampal tissue damage was determined using hematoxylin and eosin and Nissl staining. Mouse learning and memory ability in each group was assessed by the Morris water maze test, and the expression levels of mammalian target of rapamycin (mTOR) signal molecules and ferroptosis-related proteins transferrin receptor 1 (TFR1), SLC7A11 and glutathione peroxidase 4 were examined by western blotting. RESULTS: Dex enhanced lipid peroxidation and iron influx in mouse HNs in both in vitro and in vivo experiments, while inhibition of the mTOR axis blocked this process. These findings demonstrate that Dex can inhibit ferroptosis-induced damage in mouse HNs by activating mTOR-TFR1 signaling to regulate ferroptosis-associated proteins, thus alleviating cognitive dysfunction in AD mice. CONCLUSION: Dex can activate the mTOR-TFR1 axis to inhibit ferroptosis in mouse HNs, thereby improving the learning and memory ability of mice.
ABSTRACT
BACKGROUND: Metagenomic next-generation sequencing (mNGS) is a new method that combines high-throughput sequencing and bioinformatics analysis. However, it has not become as popular due to the limited testing equipment and high costs and lack of family awareness with not much relevant intensive care unit (ICU) research data. OBJECTIVE: To explore the clinical use and value of metagenomics next-generation sequencing (mNGS) in patients with sepsis in the ICU. METHODS: We conducted a retrospective analysis of 102 patients with sepsis admitted to the ICU of Peking University International Hospital from January 2018 to January 2022. Based on whether mNGS was performed, the identified patients were divided into the observation group (n= 51) and the control group (n= 51), respectively. Routine laboratory tests, including routine blood test, C-reactive protein, procalcitonin, and culture of suspicious lesion specimens were performed in both groups within 2 hours after admission to the ICU, while mNGS tests were performed in the observation group. Patients in both groups were routinely given initial anti-infective, anti-shock, and organ support treatment. Antibiotic regimens were optimized in a timely manner according to the etiological results. Relevant clinical data were collected. RESULTS: The testing cycle of mNGS was shorter than that of the conventional culture (30.79 ± 4.01 h vs. 85.38 ± 9.94 h, P< 0.001), while the positive rate of mNGS was higher than that of the conventional culture (82.35% vs. 45.1%, P< 0.05), with obvious superiority in the detection of viruses and fungus. There were significant differences in the optimal time of antibiotics (48 h vs.100 h) and length of ICU stay (11 d vs. 16 d) between the observation group and control group (P< 0.01) respectively, with no difference in 28-day mortality (33.3% vs. 41.2%, P> 0.05). CONCLUSION: mNGS is useful in the detection of sepsis-causing pathogens in the ICU with the advantages of short testing time and high positive rate. There was no difference in the 28-day outcome between the two groups, which may be related to other confounding factors such as small sample size. Additional studies with extended sample size are needed.
