Effects of dexmedetomidine on depression-like behaviour in chronic restraint stress mice: Involvement of specific brain regions.

It is crucial to develop novel antidepressants. Dexmedetomidine (DEX) can exert antidepressant effects, but its underlying mechanism remains unclear. We used chronic restraint stress (CRS) to induce depression-like behaviour in mice and administered low-dose DEX (2 µg/kg per day) during CRS modelling or one injection of high-dose DEX (20 µg/kg) after CRS. The results of the behavioural tests revealed that both methods ameliorated CRS-induced depression. The brain slices of the mice were subjected to immunohistochemical staining for c-fos and phosphorylated ERK (pERK). Results showed that the continuous low-dose DEX-treated group, but not the single high-dose DEX-treated group expressed less c-fos in the nucleus locus coeruleus (LC) with a mean optical density (MOD) of 0.06. Other brain regions, including the dentate gyrus (DG), pyriform cortex (Pir), anterior part of paraventricular thalamic nucleus (PVA), arcuate nucleus (Arc), and core or shell of accumbens nucleus (Acbc or Acbs), presented differences in c-fos expression. In contrast, the low-dose DEX-treated group exhibited three-fold greater pERK expression in the LC of the CRS mice, with a MOD of 0.15. Pir, cingulate cortex (Cg) and, anterior and posterior part of paraventricular thalamic nucleus (PVA and PVP) exhibited pERK expression differences due to distinct reagent treatments. These changes indicate that the responses of brain regions to different DEX administration methods and doses vary. This study confirmed the ability of DEX to ameliorate CRS-induced depression and identified candidate target brain regions, thus providing new information for the antidepressant mechanism of DEX.

Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.

INTRODUCTION: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods. RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor. CONCLUSION: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

Effects of Dexmedetomidine Added to Ropivacaine in Ultrasound-Guided Continuous Pericapsular Nerve Group Block Among Elderly Patients Undergoing Total Hip Arthroplasty.

Total hip arthroplasty (THA) is a highly effective intervention for addressing hip joint issues, yet managing perioperative pain remains a significant challenge. In this study, we aimed to investigate the impact of supplementing ropivacaine with dexmedetomidine in ultrasound-guided continuous pericapsular nerve group block (PENGB) among elderly patients undergoing THA. We conducted a retrospective analysis involving 112 elderly patients who underwent THA. These patients were divided into two groups: the Control group, receiving ropivacaine alone, and the DEX group, receiving ropivacaine combined with dexmedetomidine. We evaluated various parameters including hemodynamic data, postoperative pain levels assessed using the Visual Analog Scale, cognitive status measured with the Montreal Cognitive Assessment, and serum markers (S100ß and GFAP). Our findings revealed that the DEX group exhibited improved stability in blood pressure and oxygen saturation following surgery. Moreover, patients in the DEX group reported significantly lower levels of pain at 6 and 12 hours postsurgery, with a prolonged duration of pain relief. Furthermore, dexmedetomidine administration was associated with preserved cognitive function during the early postoperative period. Analysis of serum markers suggested potential cognitive protection conferred by the addition of dexmedetomidine. Overall, our study underscores the multifaceted benefits of incorporating dexmedetomidine into ropivacaine-based PENGB for elderly THA patients.

The antagonistic effect of FTO on METTL14 promotes AKT3 m6A demethylation and the progression of esophageal cancer.

BACKGROUND: As the most abundant modification in eukaryotic messenger RNAs (mRNAs), N6-methyladenosine (m6A) plays vital roles in many biological processes. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen for m6A targets in esophageal cancer cells and patients. The role of m6A RNA methylase in esophageal cancer was also analyzed using bioinformatics. In vitro and in vivo experiments were used to analyze gene expression and function. CCK-8, colony formation, cell apoptosis and immunofluorescence staining assays were performed to evaluate the proliferation, migration and invasion of esophageal cancer cells, respectively. Western blot analysis, RNA stability, RIP and luciferase reporter assays were performed to elucidate the underlying mechanism involved. RESULTS: We found that the m6A demethylase FTO was significantly upregulated in esophageal cancer cell lines and patient tissues. In vivo and in vitro assays demonstrated that FTO was involved in the proliferation and apoptosis of esophageal cancer cells. Moreover, we found that the m6A methyltransferase METTL14 negatively regulates FTO function in esophageal cancer progression. FTO alone is not related to the prognosis of esophageal cancer, and its function is antagonized by METTL14. By using transcriptome-wide m6A-seq and RNA-seq assays, we revealed that AKT3 is a downstream target of FTO and acts in concert to regulate the tumorigenesis and metastasis of esophageal cancer. Taken together, these findings provide insight into m6A-mediated tumorigenesis in esophageal cancer and could lead to the design of new therapeutic strategies.

Lidocaine aerosol preoperative application for improving the comfort of pediatric patients undergoing tonsillectomy and adenoidectomy: A prospective randomized controlled trial.

Background and Aims: The use of lidocaine aerosol for pediatric tonsil and adenoidectomy has been reported less frequently. We hope to improve the perioperative comfort of pediatric patients undergoing these procedures by applying lidocaine aerosol. Methods: A total of 122 pediatric patients receiving tonsil and adenoidectomy were randomly divided into a lidocaine aerosol group (Group L) and a saline group (Group C), with 61 patients in each group; 2.4% alkaline lidocaine aerosol and saline were sprayed in the pharynx before induction. Our primary outcome were the incidence and rate ratio (RR) of postoperative pharyngeal complications (oropharyngeal dryness, dysphagia, hoarseness, and sore throat) and the pharyngeal comfort score, the latter of which was assessed by the occurrence of the above complications (yes = 0 point, none = 1 point). The secondary outcomes included preoperative and intraoperative blood pressure and heart rate, the incidence of choking during the induction period, the intraoperative opioid dosage, and the pain level and depth of sedation at 2, 6, and 24 h postoperatively. Statistical software used in this study included PASS15.0, SPSS 26.0, and GraphPad Prism 9.3.1, and statistical methods used included the t-test, the χ² test, the Mann-Whitney U test, and the repeated measures analysis of variance. Results: The incidence and RR of postoperative pharyngeal complications such as oropharyngeal dryness (RR: 0.667, 95% confidence interval [CI]: 0.458-0.970, p = 0.03), dysphagia (RR: 0.333, 95% CI: 0.114-0.976, p = 0.03), hoarseness (RR: 0.647, 95% CI: 0.433-0.967, p = 0.03), and sore throat (RR: 0.727, 95% CI: 0.547-0.967, p = 0.03) were significantly lower in Group L than in Group C at 2 h postoperatively, and the incidence and RR of postoperative sore throat was significantly lower in Group L than in Group C at 6 h postoperatively (RR: 0.717, 95% CI: 0.547-0.942, p = 0.01). The postoperative pharyngeal comfort scores were significantly higher in Group L than in Group C at all postoperative time points (p < 0.05). The Ramsay sedation score was significantly higher (p < 0.01) and FLACC (face, legs, activity, crying, and consolability) score was significantly lower (p < 0.01) in Group L than in Group C at 2 h postoperatively. In Group C, the blood pressure and heart rate significantly faster at all time points immediately after intubation and afterward, except at the end of surgery (p < 0.05). Conclusions: In pediatric tonsil and adenoidectomy, the application of lidocaine aerosol before induction can reduce the incidence of postoperative pharyngeal complications, improve the child's postoperative pharyngeal comfort, and better realize perioperative "comfort medical treatment."

Ischemia reperfusion myocardium injuries in type 2 diabetic rats: Effects of ketamine and insulin on LC3-II and mTOR expression.

Objectives: Myocardiopathy occurs in ischemia-induced injury caused by dysregulation of autophagy of cardiac tissues. The present report evaluates the protective effect of ketamine and insulin against myocardial injury in type 2 diabetic rats (T2DM).Methods: The effects of ketamine and its combination with insulin on biochemical parameters and inflammatory cytokines in the serum of I/R-induced myocardial injury in T2DM rats were evaluated. The parameters of reactive oxygen species and the expression of autophagosome signaling pathway proteins were also determined. Using transmission electron microscopy, we investigated autophagosomes. Western blots were used to detect autophagy-associated signaling pathways. Myocardial function was determined by echocardiography and histopathological changes in myocardial tissues were also determined in I/R-induced myocardial injury in type 2 diabetic rats.Results: There was a significant reduction in glucose, AST, LDH, and CK-MB levels and cytokines (IL-1ß, IL-6, and TNF-α) in serum of the ketamine (p < .05) and ketamine + insulin (p < .01) groups than in the diabetic + I/R. MDA and ROS levels were reduced with a substantial (p < .05) increase in GSH levels through improved cardiac function in the ketamine (p < .05) and ketamine + insulin (p < .01) groups than the diabetic + I/R group. There was an increase in mature autophagosomes in diabetic+I/R+Kt+In compared to diabetic+I/R+Kt alone in infarction and marginal zones. It should be noted that the significant increase (p < .01) in protein levels of the autophagy-associated intracellular signaling pathways AMPK and mTOR, as well as an increase in LC3-II and BECLIN-1, suggests that ketamine combined with insulin-activated autophagy-associated intracellular signaling AMPK and mTOR.Conclusion: The findings of the study suggest that ketamine combined with insulin administration remarkably protects I/R-induced myocardial injury in rats with T2DM by reducing the dysregulation of autophagy.

The effect of dexmedetomidine on the post operation recovery of gastrointestinal function undergoing intestinal surgery: implications for retired athletes

Objective: To investigate the effect of dexmedetomidine on the recovery of gastrointestinal function after intestinal surgery. Methods: A total of 94 cases of gastrointestinal endoscopic surgery in our hospital from February 2020 to April 2022 were selected and randomly divided into dexmedetomidine group (group D, n=47) and control group (group C, n=47), There is no restriction on gender and age. Group E was given 1 μg/kg of dexmedetomidine before induction of anesthesia, and 0.5 μg/kg.h was pumped during the maintenance period of anesthesia. Group C was given an equal volume of normal saline. Heart rate (HR) and mean arterial pressure (MAP) were recorded at five time points before anesthesia (T0), after intubation (T1), skin incision (T2), after skin incision 1h (T3), and at the end of surgery (T4). BIS, intraoperative dosage of propofol and remifentanil, VAS score and Ramsay sedation score at 24h, 48h, 72h after operation, I-FEED scoreand bowel sound recovery time at 24h, 48h, 72h, 96h after operation, exhaust time, eating time, defecation time, and discharge time. Results: Compared with group C, the MAP and HR of group D were more stable, the consumption of anesthetics in group D was significantly lower, and the VAS score of group E was lower than that of group C at 24, 48, and 72 hours after operation (P<0.05). The I-FEED score at 24h, 48h, 72h, and 96h after operation and the incidence of PONV and POGD in group D were lower than those in group C (P＜0.05). Postoperative bowel sounds recovery time, exhaust time, eating time, defecation time and hospitalization days in group D were lower than those in group C, and the difference was statistically significant (P<0.05). Conclusion: Dexmedetomidine is applied in intestinal surgery, it can stabilize the induction period and intraoperative hemodynamics, reduce the amount intraoperative anesthetics, promote the recovery of gastrointestinal function, and accelerate the recovery of athletic patients. (AU)

Effect of different modes of administration of dexmedetomidine on the quality of recovery in ambulatory thyroidectomy: a randomized, controlled trial.

OBJECTIVE: To compare the effects of two different administration methods of dexmedetomidine (DEX) used as an adjuvant to ropivacaine in ultrasound-guided bilateral intermediate cervical plexus block (CPB) in terms of efficacy and the duration of postoperative analgesia in patients undergoing ambulatory thyroidectomy. METHODS: This double-blind, randomized study enrolled patients who underwent thyroidectomy with ultrasound-guided bilateral intermediate CPB. Patients were randomized to receive either perineural administration of dexmedetomidine (group DP) or intravenous pumping of dexmedetomidine (group DI). The 40-item Quality of Recovery (QoR-40) questionnaire was used to assess the primary endpoint, which was the global QoR-40 score 24 h after the operation. RESULTS: Sixty patients were randomized equally into the two groups. The total QoR-40 score 24 h postoperatively was significantly higher in group DP than group DI (160.6 ± 9.1 versus 152.8 ± 7.9, respectively). Dimensions of physical comfort and pain scores were significantly higher in group DP than group DI. The visual analogue scale pain score scores were significantly lower in group DP than group DI at 12 and 24 h postoperatively. CONCLUSIONS: DEX as an adjuvant to ropivacaine in ultrasound-guided intermediate CPB can improve the QoR-40 score and prolong postoperative analgesia.Trial registration number: ChiCTR2000031264 at www.chictr.org.cn on 26 March 2020.

The Value of the Optic Nerve Sheath Diameter (ONSD) in Predicting Postdural Puncture Headache (PDPH): A Prospective Observational Study.

BACKGROUND: Postdural puncture headache (PDPH) is one of the serious complications after lumbar puncture, but there is no effective tool to predict it. OBJECTIVES: To explore whether ultrasound measurement of optic nerve sheath diameter (ONSD) as a predictor of PDPH can be a reliable tool supported by reliable protocols and data. STUDY DESIGN: A prospective observational study. SETTING: Department of Anesthesiology. METHODS: This prospective observational study was performed in 156 patients undergoing cesarean section (CS). The patient's ONSD was recorded before anesthesia (T0), 10 minutes after anesthesia (T1), at the end of the operation (T2), at the first postoperative day (T24), at the second postoperative day (T48), and the third postoperative day (T72). During the 3-day follow-up, the patients were evaluated, identified, and divided into a PDPH group and a non-PDPH group. Age, weight, height, ASA, lumbar puncture location, and the number of lumbar puncture attempts were also recorded. We mainly analyzed the changes and differences between the 2 groups of ONSD. RESULTS: Twenty-four patients (15%) developed PDPH. The ONSD was significantly lower in the PDPH group than in the non-PDPH group at T2, T24, T48, and T72. All patients showed a significant reduction in ONSD at T1 compared to T0. Women whose ONSD continued to fall without recovery from T0 to T2 were more likely to experience PDPH (RR 5. 022; 95 CI 3.343 to 7.508). The ONSD at T24 was the best predictor of PDPH (ACU 0. 9787, 95 CI 0.9578 to 0.9996), with a cutoff value of 0.40 cm (sensitivity 92%, specificity 94%). LIMITATIONS: This is a single-center study, and ONSD may vary in different regions or ethnic groups. CONCLUSIONS: We believe that continuous measurements of ONSD may be a useful tool for predicting PDPH.

Application of opioid-free general anesthesia for gynecological laparoscopic surgery under ERAS protocol: a non-inferiority randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) is now widely used in various surgical fields including gynecological laparoscopic surgery, but the advantages of opioid-free anesthesia (OFA) in gynecological laparoscopic surgery under ERAS protocol are inexact. AIMS: This study aims to assess the effectiveness and feasibility of OFA technique versus traditional opioid-based anesthesia (OA) technique in gynecological laparoscopic surgery under ERAS. METHODS: Adult female patients aged 18 ~ 65 years old undergoing gynecological laparoscopic surgery were randomly divided into OFA group (Group OFA, n = 39) with esketamine and dexmedetomidine or OA group (Group OA, n = 38) with sufentanil and remifentanil. All patients adopted ERAS protocol. The primary outcome was the area under the curve (AUC) of Visual Analogue Scale (VAS) scores (AUCVAS) postoperatively. Secondary outcomes included intraoperative hemodynamic variables, awakening and orientation recovery times, number of postoperative rescue analgesia required, incidence of postoperative nausea and vomiting (PONV) and Pittsburgh Sleep Quality Index (PSQI) perioperatively. RESULTS: AUCVAS was (Group OFA, 16.72 ± 2.50) vs (Group OA, 15.99 ± 2.72) (p = 0.223). No difference was found in the number of rescue analgesia required (p = 0.352). There were no between-group differences in mean arterial pressure (MAP) and heart rate (HR) (p = 0.211 and 0.659, respectively) except MAP at time of surgical incision immediately [(Group OFA, 84.38 ± 11.08) vs. (Group OA, 79.00 ± 8.92), p = 0.022]. Times of awakening and orientation recovery in group OFA (14.54 ± 4.22 and 20.69 ± 4.92, respectively) were both longer than which in group OA (12.63 ± 3.59 and 18.45 ± 4.08, respectively) (p = 0.036 and 0.033, respectively). The incidence of PONV in group OFA (10.1%) was lower than that in group OA (28.9%) significantly (p = 0.027). The postoperative PSQI was lower than the preoperative one in group OFA (p = 0.013). CONCLUSION: In gynecological laparoscopic surgery under ERAS protocol, OFA technique is non-inferior to OA technique in analgesic effect and intraoperative anesthesia stability. Although awakening and orientation recovery times were prolonged compared to OA, OFA had lower incidence of PONV and improved postoperative sleep quality. TRIAL REGISTRATION: ChiCTR2100052761, 05/11/2021.

The effects of hepatic ischemia/reperfusion injury on postoperative cognitive function in aged rats.

Introduction: Hepatic ischemia/reperfusion injury (I/R) is a significant source of morbidity and mortality after liver surgery. The aim of this study was to investigate the effect of hepatic I/R injury on the hippocampus in rats with postoperative cognitive dysfunction (POCD). Material and methods: Adult male Sprague-Dawley rats (n = 160, age: 20-25 months, weight: 300-350 g) received I/R surgery with ischemia for 20 min, 30 min, and 40 min in different groups. Behavior tests of the Morris water maze (MWM) test and the passive avoidance test were applied. Population spike (PS) of pyramidal cells, nuclear factor κB (NF-κB) and protein kinase γ (PKCγ) in the hippocampus were observed. Results: Within 10 days after surgery, in aged rats with varying impaired cognitive function, spike size and spike latency period were reduced, level of PKCγ was decreased and an increased level of NF-κB was observed in the I/R group, especially in the I/R group with ischemia for 40 min. The parameters showed no significant difference in rats in the I/R group compared with the sham group at the 18th day after surgery. Conclusions: Hepatic I/R injury has a negative impact on the postoperative cognitive function in aged rats, leading to hippocampus changes with PS abnormity and level changes of NF-κB, PKCγ. However, this cognitive deficit improved over time.

Propofol Versus Sevoflurane General Anaesthesia for Selective Impairment of Attention Networks After Gynaecological Surgery in Middle-Aged Women: A Randomised Controlled Trial.

Purpose: Attention is an essential component of cognitive function that may be impaired after surgery with anaesthesia. Propofol intravenous anaesthesia and sevoflurane inhalational anaesthesia are frequently used in gynaecological surgery. However, which type of anaesthetic has fewer cognitive effects postoperatively remains unclear. We compared the differences in attention network impairment after surgery in women receiving propofol versus sevoflurane general anaesthesia. Patients and Methods: Eighty-three patients with gynaecological diseases who were 40-60 years of age were involved in the study. All patients underwent elective gynaecological surgery under either total intravenous anaesthesia or sevoflurane inhalational anaesthesia, depending on randomisation. The efficiencies of the three attention networks were captured using the attention network test preoperatively and on the 1st and 5th postoperative days. Results: Both groups of patients showed differences in impairments on the 1st and 5th postoperative days. Pairwise comparisons indicated that the alerting and orienting networks of patients in the propofol group were impaired to a greater extent than those of patients in the sevoflurane group on the 1st postoperative day, while the executive control network was impaired to a lesser extent. On the 5th postoperative day, the alerting networks of both groups recovered to the baseline level. Patients in the propofol group still showed impairment of the orienting network, while patients in the sevoflurane group recovered to baseline. For the executive control network, patients in the sevoflurane group still exhibited more severe impairment than those in the propofol group. Conclusion: In middle-aged women, propofol impaired orienting and alerting networks more than sevoflurane, while sevoflurane showed more residual impairment of the executive control network.

A novel epithelial-mesenchymal transition gene signature for the immune status and prognosis of hepatocellular carcinoma.

BACKGROUND: This study clarified whether EMT-related genes can predict immunotherapy efficacy and overall survival in patients with HCC. METHODS: The RNA-sequencing profiles and patient information of 370 samples were derived from the Cancer Genome Atlas (TCGA) dataset, and EMT-related genes were obtained from the Molecular Signatures database. The signature model was constructed using the least absolute shrinkage and selection operator Cox regression analysis in TCGA cohort. Validation data were obtained from the International Cancer Genome Consortium (ICGC) dataset of patients with HCC. Kaplan-Meier analysis and multivariate Cox analyses were employed to estimate the prognostic value. Immune status and tumor microenvironment were estimated using a single-sample gene set enrichment analysis (ssGSEA). The expression of prognostic genes was verified using qRT-PCR analysis of HCC cell lines. RESULTS: A signature model was constructed using EMT-related genes to determine HCC prognosis, based on which patients were divided into high-risk and low-risk groups. The risk score, as an independent factor, was related to tumor stage, grade, and immune cells infiltration. The results indicated that the most prognostic genes were highly expressed in the HCC cell lines, but GADD45B was down-regulated. Enrichment analysis suggested that immunoglobulin receptor binding and material metabolism were essential in the prognostic signature. CONCLUSION: Our novel prognostic signature model has a vital impact on immune status and prognosis, significantly helping the decision-making related to the diagnosis and treatment of patients with HCC.

Propofol Protects Against Erastin-Induced Ferroptosis in HT-22 Cells.

Propofol is a short-acting intravenous anesthetic that is widely used in clinical treatment. Previous articles have indicated that propofol is a therapeutic target for anti-apoptosis, anti-inflammation, anti-lipid peroxidation, and anti-reactive oxygen species (ROS). Moreover, cell ferroptosis is strongly correlated with cellular ROS, inflammatory responses, and lipid peroxidation. However, the mechanisms by which propofol attenuates neuronal injury by reducing ferroptosis remain unknown. Hence, we hypothesized that propofol could protect neurons by reducing ferroptosis. To test this hypothesis, HT-22 cells were treated with a specific ferroptosis activator (erastin) in the presence of propofol (50 µM). We found that propofol reduced erastin-induced high Fe2+ concentrations, lipid peroxides, and excess ROS. Western blotting results also suggested that propofol could rescue erastin-induced low expression of GXP4 and system Xc-. Further experiments indicated that propofol attenuated p-ALOX5 expression at Ser663 independent of ERK. In addition, we built two transient transfection cell lines, ALOX5 OE and Ser663Ala-ALOX5 OE, to confirm the target of propofol. We found that the Ser663 point is the critical role of propofol in rescuing erastin-induced cell injury/lipid peroxidation. In conclusion, propofol may help attenuate ferroptosis, which may provide a new therapeutic method to treat neuronal injury or the brain inflammatory response.

4.8% sevoflurane induces activation of autophagy in human neuroblastoma SH-SY5Y cells by the AMPK/mTOR signaling pathway.

Prolonged sevoflurane exposure leads to neurotoxicity. Autophagy plays an important role in promoting cell survival in different conditions. However, the role and mechanism of autophagy in sevoflurane-induced neurotoxicity were not fully elucidated. We attempted to indicate whether sevoflurane could activate the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)-mediated autophagy to attenuate anesthetics-induced neuronal injury in this study. Sevoflurane treatment significantly decreased the cell viability and induced apoptosis of SH-SY5Y cells. The expression level of Bcl-2 decreased, while that of Bax remarkably increased. Meanwhile, autophagy was activated by sevoflurane exposure as evidenced by increased expression levels of autophagy-related proteins (LC3-II and Atg5), decreased expression level of autophagic substrate P62, and increased autophagosomes and autolysosomes. Further autophagosomes and fewer autolysosomes were observed in the presence of Bafilomycin A1, an autolysosomes degradation inhibitor, suggesting that sevoflurane induced autophagic flux rather than inhibiting degradation of autophagy. Activation of autophagy by rapamycin partly reversed the sevoflurane-decreased cell viability. In contrast, inhibition of autophagy by 3-Methyladenine (3-MA) or Atg5-targeted small interfering RNA (siRNA) aggravated the sevoflurane-induced neurotoxicity. Further examination revealed that sevoflurane-induced autophagy was mediated by the AMPK/mTOR signaling pathway, with increased p-AMPK expression and decreased p-mTOR expression. Collectively, these results indicated that sevoflurane activates autophagy by regulating the AMPK/mTOR signaling pathway, which is protective against sevoflurane-induced damage in SH-SY5Y cells. Our results may assist clinicians to develop further promising therapeutic strategies for the neurotoxicity induced by inhaled anesthetics.

Efficacy and safety of repeated esketamine intravenous infusion in the treatment of treatment-resistant depression: A case series.

Repeated intravenous administration of esketamine may increase and prolong the treatment efficacy of depressive patients. Firstly, the patient received esketamine (0.4 mg/kg intravenous over 40 min) infusion every other day, and totally 6 times infusion. If the patient's symptoms cannot improve, they got another 6 times esketamine injection (one time per day, 0.4 mg/kg intravenous over 40 min). Our study reported that 12 times intravenous esketamine infusion adjunctive with oral antidepressants sustained the efficacy for 6 months at least. These cases provide evidence of the safety and longtime efficacy of repeated intravenous esketamine for the treatment of treatment resistant depression.

[Effects of low-dose dexmedetomidine combined with hydromorphone in postoperative analgesia and on the serum IL-6 and CRP levels of prostate cancer patients].

OBJECTIVE: To explore the effects of low-dose dexmedetomidine (DM) combined with hydromorphone (HM) in postoperative analgesia and on levels of serum interleukin-6 (IL-6) and C-reactive protein (CRP) in PCa patients. METHODS: Using the random number table, we divided 102 PCa patients undergoing radical prostatectomy from January 2019 to November 2020 into a trial group (n = 51) and a control group (n = 51), the former given HM and the latter low-dose DM + HM for postoperative analgesia. We recorded the postoperative resuscitation time, extubation time and pain, perioperative cognitive function, IL-6 and CRP levels, and drug-related adverse reactions of the patients, and compared them between the two groups. RESULTS: There was no statistically significant difference in postoperative resuscitation time and extubation time between the two groups of patients (P > 0.05). The frequency of patient-controlled epidural analgesia (PCEA) compressions was lower in the trial than in the control group within 24 hours after surgery (P < 0.05). The Visual Analogue Scale (VAS) scores were higher in both of the groups at 24 hours than at 4, 12, and 48 hours after surgery (P < 0.05), at 12 hours than at 4 and 48 hours (P < 0.05) and at 4 hours than at 48 hours (P < 0.05), but lower in the trial than in the control group at 4, 12 and 24 hours postoperatively (P < 0.05). No statistically significant difference was observed in the scores of the Mini Mental State Evaluation Scale between the two groups of patients (P > 0.05). The levels of IL-6 and CRP were higher in both of the groups at 24 hours after than before and at 4, 12 and 48 hours after surgery (P < 0.05), at 48 hours after than before and at 4 and 12 hours after surgery (P < 0.05), at 12 hours after than before and at 4 hours after surgery (P <0.05), and at 4 hours after than before surgery (P < 0.05), but lower in the trial than in the control group at 4, 12, 24 and 48 hours postoperatively (P < 0.05). There was no statistically significant difference in the total incidence rate of adverse reactions between the two groups (P > 0.05). CONCLUSIONS: Low-dose dexmedetomidine combined with hydromorphone is a safe and effective option for postoperative analgesia in PCa patients, and it can inhibit the expression of inflammatory factors.

Quality Evaluation of Rock Mass Using RMR14 Based on Multi-Source Data Fusion.

The uncertainties in quality evaluations of rock mass are embedded in the underlying multi-source data composed by a variety of testing methods and some specialized sensors. To mitigate this issue, a proper method of data-driven computing for quality evaluation of rock mass based on the theory of multi-source data fusion is required. As the theory of multi-source data fusion, Dempster-Shafer (D-S) evidence theory is applied to the quality evaluation of rock mass. As the correlation between different rock mass indices is too large to be ignored, belief reinforcement and Murphy's average belief theory are introduced to process the multi-source data of rock mass. The proposed method is designed based on RMR14, one of the most widely used quality-evaluating methods for rock mass in the world. To validate the proposed method, the data of rock mass is generated randomly to realize the data fusion based on the proposed method and the conventional D-S theory. The fusion results based on these two methods are compared. The result of the comparison shows the proposed method amplifies the distance between the possibilities at different ratings from 0.0666 to 0.5882, which makes the exact decision more accurate than the other. A case study is carried out in Daxiagu tunnel in China to prove the practical value of the proposed method. The result shows the rock mass rating of the studied section of the tunnel is in level III with the maximum possibility of 0.9838, which agrees with the geological survey report.