Circular RNA DLGAP4 alleviates sevoflurane-induced neurotoxicity by regulating miR-9-5p/Sirt1/BDNF pathway.

BACKGROUND: Sevoflurane is a widely used anesthetic in infants. However, long and repeated exposure to this drug can cause developmental neurotoxicity. This study aimed to investigate the role and mechanism of circular RNA DLGAP4 (circDLGAP4) in sevoflurane-induced neurotoxicity. METHODS: Neonatal mice and mouse hippocampal neuronal cell line HT22 were used to construct sevoflurane-induced nerve injury models. The role of circDLGAP4 in sevoflurane-induced neurotoxicity was evaluated by gain-and/or loss-of-function methods. Pathological alterations in hippocampus were analyzed by hematoxylin-eosin and Tunel staining. Cell injury was assessed by cell viability and apoptosis, which was detected by CCK-8 and flow cytometry. The expression of circDLGAP4 and miR-9-5p was determined by real-time PCR. Sirt1 and BDNF levels were measured by Western blot. Productions of TNF-α and IL-6 were examined by ELISA. Dual-luciferase reporter assay and/or RNA pull-down assay were used to confirm the direct binding among circDLGAP4, miR-9-5p, and Sirt1. Rescue experiments were used to further verify the mechanism of circDLGAP4. RESULTS: CircDLGAP4 expression was decreased by sevoflurane both in vivo and in vitro. Overexpression of circDLGAP4 elevated cell viability, reduced apoptosis and levels of TNF-α and IL-6, while circDLGAP4 knockdown showed the opposite effects in sevoflurane-induced HT22 cells. Mechanically, circDLGAP4 functioned via directly binding to and regulating miR-9-5p, followed by targeting the Sirt1/BDNF pathway. Additionally, circDLGAP4 upregulation relieved sevoflurane-induced nerve injury, reduced levels of TNF-α, IL-6 and miR-9-5p, but increased the expression of Sirt1 and BDNF in hippocampus. CONCLUSIONS: Our studies found that circDLGAP4 relieved sevoflurane-induced neurotoxicity by sponging miR-9-5p to regulate Sirt1/BDNF pathway.

Predictive value of ELWI combined with sRAGE/esRAGE levels in the prognosis of critically ill patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition. Accurate judgement of the disease progression is essential for controlling the condition in ARDS patients. We investigated whether changes in the level of serum sRAGE/esRAGE could predict the 28-day mortality of ICU patients with ARDS. A total of 83 ARDS patients in the ICU of the Second Affiliated Hospital of Nantong University from January 2021 to June 2022 were consecutively enrolled in this study. Demographic data, primary diagnosis and comorbidities were obtained. Multiple scoring systems, real-time monitoring systems, and biological indicators were determined within 6 h of admission. The clinical parameters for survival status of the ARDS patients were identified by multivariate logistic regression. Receiver operating characteristic (ROC) curve analysis was employed to verify the accuracy of the prognosis of the related parameters. The admission level of sRAGE was significantly higher in the nonsurvival group than in the survival group (p < 0.05), whereas the serum esRAGE level showed the opposite trend. Multivariate logistic regression analysis showed that sRAGE (AUC 0.673, p < 0.05), esRAGE (AUC 0.704, p < 0.05), and ELWI (extravascular lung water index) (AUC 0.717, p < 0.05) were independent risk factors for the prognosis of ARDS. Model B (ELWI + esRAGE) could not be built as a valid linear regression model (ELWI, p = 0.079 > 0.05). Model C (esRAGE + sRAGE) was proven to have no significance because it had a predictive value similar to that of the serum levels of esRAGE (Z = 0.993, p = 0.351) or sRAGE (Z = 1.116, p = 0.265) alone. Subsequently, Model D (sRAGE + esRAGE + ELWI) showed the best 28-day mortality predictive value with a cut-off value of 0.426 (AUC 0.841; p < 0.001), and Model A (sRAGE + ELWI) had a cut-off value of 0.401 (AUC 0.820; p < 0.001), followed by sRAGE (AUC 0.704, p = 0.004), esRAGE (AUC 0.717, p = 0.002), and ELWI (AUC 0.637, p = 0.028). In addition, there was no statistically significant difference between Model A and Model D (Z = 0.966, p = 0.334). The admission level of sRAGE was higher in the nonsurvival group, while the serum esRAGE level showed the opposite trend. Model A and Model D could be used as reliable combined prediction models for predicting the 28-day mortality of ARDS patients.

Effect of dexmedetomidine for sedation and cognitive function in patients with preoperative anxiety undergoing carotid artery stenting.

OBJECTIVE: This study was performed to examine the effect of dexmedetomidine for intraoperative sedation and postoperative cognitive function in patients with preoperative anxiety undergoing carotid artery stenting. METHODS: Eighty patients were randomly divided into two groups: the dexmedetomidine group and the control group. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Anxiety was evaluated using the Amsterdam Preoperative Anxiety and Information Scale. Routine monitoring indices were recorded during surgery, and cognitive function indices were recorded before drug infusion (T0), 10 minutes after drug infusion (T1), at the end of surgery (T2), and 6 hours after surgery (T3). RESULTS: The anxiety scores were not significantly different between the two groups at T0, but they became significantly different at T1-3. The MMSE scores in both groups increased at 1 and 7 days postoperatively; although the increase in the dexmedetomidine group was sharper, there was no significant difference. In both groups, the MMSE scores at 1 and 7 days after surgery were not significantly different from those at 1 day before surgery. CONCLUSION: Dexmedetomidine can improve patients' anxiety and achieve a sufficient sedation effect without causing postoperative cognitive dysfunction.

Activation of mTOR in the spinal cord is required for pain hypersensitivity induced by chronic constriction injury in mice.

BACKGROUND: The mammalian target of rapamycin (mTOR) is known to regulate cell growth, and it also participates in pain transmission as has been recently verified in inflammatory and neuropathic pain models. The targeting of mTOR represents a new strategy for the control of chronic pain. In the present study, we investigated the effect of mTOR in the expression of PSD95 and NR2B-PSD95 or GluA2-PSD95 interaction ratio in a chronic constriction injury (CCI) mice model. METHODS: Paw mechanical withdrawal threshold (PMWT) and paw withdrawal thermal latency (PWTL) were respectively used to assess mechanical allodynia and thermal hyperalgesia after CCI operation and intrathecal injection of rapamycin. Western blot and co-immunoprecipitation were used to investigate the effects of rapamycin on the expression of PSD95 and interaction ratio of NR2B-PSD95 or GluA2-PSD95 in the spinal dorsal horn of mice. RESULTS: Our study demonstrated that the inhibition of spinal mTOR with intrathecal injections of rapamycin (1 µg/5 µL) for days 1-6 after CCI surgery led to an obvious decrease in CCI-induced neuropathic pain. Rapamycin significantly reduced the PMWT of CCI mice, whereas there was no significant effect on PWTL. The active form of the mTOR signaling pathway (p-mTOR, p-4EBP1 and p-p70S6k) at the spinal level remarkably increased in CCI mice, and rapamycin could inhibit this up-regulation. The increased expression of PSD95 and the interaction ratio of GluA2-PSD95 or NR2B-PSD95 could also be inhibited by intrathecal injection of rapamycin. CONCLUSION: These data suggest that the mTOR pathway is activated in the spinal dorsal horn in CCI-induced neuropathic pain, and the intrathecal injection of rapamycin can reduce mechanical allodynia. Our findings indicate that spinal mTOR is an important component of CCI-induced neuropathic pain, and mTOR may be a potential target for chronic pain therapy.

[Pharmaceutical characteristics of Glycyrrhizae radix micropowder].

OBJECTIVE: To characterize the micromeritic properties and in vitro dissolution of common powder and micropowder of Glycyrrhizae radix and explore the application of micronization technique in preparation of the drug. METHODS: The morphological and cellular characteristics of the 4 powders of Glycyrrhizae radix were examined microscopically, and their angle of repose and size distribution were measured. The content of licoflavone and liquirtin in the powders were determined by high-performance liquid chromatography and ultraviolet spectrophotometry, respectively. The dissolution rate of the active ingredients in the micropowder and common powder was studied by constant temperature mixing dissolution method. RESULTS: Significant differences were observed between common powder and micropowder in particle characteristics and surface morphology. The dissolution rates and the concentrations of the corresponding ingredients in the micropowder were higher than the common powder. CONCLUSION: Micronization is helpful for better utilization of the active components in Glycyrrhizae radix.