Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. Using microarray analyses, we comprehensively compared long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) expression profiles in hippocampal tissues from a mouse model of POCD and control mice. A total of 175 lncRNAs, 117 mRNAs, and 26 miRNAs were differentially expressed between POCD and control mice. Gene ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of dysregulated genes. Correlated coding-noncoding co-expression (CNC) and competing endogenous RNA (ceRNA) expression networks were constructed using bioinformatics methods. lncRNA NONMMUT000708 correlated positively with expression of the inflammation-related gene Hif3a. lncRNAs NONMMUT043249 and NONMMUT028705 mediated gene expression by binding the transcription factor cAMP response element-binding protein (CREB). The constructed ceRNA network suggested lncRNA NONMMUT055714 binds competitively with miR-7684-5p, increasing expression of its target gene, Sorl1. Finally, eight dysregulated lncRNAs, four miRNAs, and ten mRNAs were confirmed via quantitative real-time polymerase chain reaction (PCR) in 10 POCD-healthy mouse paired samples. These results suggest that lncRNAs and miRNAs are involved in POCD pathogenesis and progression. Our ceRNA network will improve understanding of lncRNA-mediated ceRNA regulatory mechanisms operating during the pathogenesis of POCD.

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In this article, we conduct a systematic review of the literature to explore the specific role of dexmedetomidine (DEX) on postoperative sleep and its associated mechanisms at present. The electronic database Embase, MEDLINE/PubMed, the Cochrane Library, Web of Science, and Google Scholar were searched. The restriction terms included "dexmedetomidine", "sleep" and "surgery". The inclusion criteria were as following: 1) patients 18 years old or older; 2) DEX used in the perioperative period not just for critically ill patients in the intensive care unit (ICU); 3) prospective or retrospective studies. The review articles, conference abstracts, and animal studies were excluded. Out of the 22 articles which met the above criteria, 20 of them were randomized controlled studies and 2 of them were retrospective cohort studies. Infusion of DEX including during the surgery and after surgery at a low or high dose was shown to improve subjective and objective sleep quality, although 2 studies showed there is no evidence that the use of DEX improves sleep quality and 1 showed less sleep efficiency and shorter total sleep time in the DEX group. Other postoperative outcomes evaluated postoperative nausea and vomiting, pain, postoperative delirium bradycardia and hypotension. Outcomes of our systematic review showed that DEX has advantages in improving patients' postoperative sleep quality. Combined with the use of general anesthetic, DEX provides a reliable choice for procedural sedation.

BackgroundThere is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder (MDD), especially treatment-resistant depression (TRD).MethodsWe searched Medline, EMBASE, and the Cochrane Library until April 1, 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response, and depressive symptoms were extracted by two independent raters. The outcome measures were Montgomery–Asberg Depression Rating Scale (MADRS) score improved from baseline, clinical response and remission, dissociative symptoms, and common adverse events. The analyses employed a random-effects model.ResultsData were synthesized from five randomized controlled trials (RCTs) employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms, and 18 subjects in cross-over designs (n = 858 with MDD, n = 792 with TRD). The weighted mean difference of MADRS score was observed to decrease by 6.16 (95% CI 4.44–7.88) in 2–4 h, 9.96 (95% CI 8.97–10.95) in 24 h, and 4.09 (95% CI 2.18–6.00) in 28 day. The pooled relative risk (RR) was 3.55 (95% CI 1.5–8.38, z = 2.89, and p < 0.001) for clinical remission and 3.22 (95% CI 1.85–5.61, z = 4.14, and p < 0.001) for clinical response at 24 h, while the pooled RR was 1.7 (95% CI 1.28–2.24, z = 3.72, and p < 0.001) for clinical remission and 1.48 (95% CI 1.17–1.86, z = 3.28, and p < 0.001) for clinical response at 28 day. Intranasal ketamine was associated with the occurrence of transient dissociative symptoms and common adverse events, but no persistent psychoses or affective switches.ConclusionOur meta-analysis suggests that repeated intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.Systematic Review RegistrationPROSPERO, CRD42020196856.

BACKGROUND: Postoperative delirium is a major debilitating complication for patients and is associated with poor outcomes. Previous studies have suggested that excessive general anesthesia may lead to postoperative delirium. Electroencephalography (EEG)-based monitors have been administered in clinical practice in an attempt to deliver appropriate anesthesia. The aim of this updated meta-analysis was to evaluate the current body of research concerning the effects of EEG-based monitor on postoperative delirium. METHODS: We conducted a meta-analysis of randomized controlled trials of the effect of processed EEG monitor on postoperative delirium as the primary outcome. The search was performed in CENTRAL, MEDLINE, and EMBASE, with no language restrictions from inception until June 23, 2019. Two independent reviewers screened records and full-text articles for inclusion. Data extraction and risk-of-bias assessment were conducted by 3 independent reviewers. Random-effects models were used to calculate combined-effect estimates. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence. RESULTS: Of 5904 records screened, 5 studies met our inclusion criteria, including 3612 patients. Meta-analysis revealed no significant effect of EEG-based monitors on postoperative delirium (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.60–1.05; I 2 = 73%). The results showed a statistically significant reduction in intensive care unit (ICU) length of stay (3 studies, weight mean difference [WMD] −0.29 days; 95% CI, −0.53 to −0.05) in patients with EEG monitored. EEG-guided anesthesia did not have a statistically significant difference in all-cause mortality (3 studies, RR, 0.63; 95% CI, 0.31–1.29) and hospital length of stay (4 studies, WMD −0.61 days; 95% CI, −1.34 to 0.11). Few studies investigated the effects of EEG-guided anesthesia on perioperative major nonneurological complications and did not come up with promising results. CONCLUSIONS: The current evidence is not sufficient to support the prevention effects of EEG monitor on postoperative delirium. More robustly designed and well-conducted studies with emphasis on this matter are warranted.

Postoperative cognitive dysfunction (POCD) is a disturbing neurological complication in patients undergoing anesthesia and surgical procedures. Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF binding to their corresponding receptors tyrosine kinase (TrkB) and p75 neurotrophin receptor (p75NTR) exert quite an opposite biological function in neuron survival and synaptic function. This study aimed to demonstrate the critical role of the BDNF/proBDNF ratio in modulating synaptic plasticity, which further leads to anesthesia-/surgery-induced POCD. It also showed that the exogenous BDNF or p75NTR inhibitor could ameliorate cognitive dysfunction. In detail, 16-month-old C57BL/6 mice were subjected to a stabilized tibial fracture surgery with isoflurane anesthesia to establish the POCD animal model. The mice were then microinjected with either p75NTR inhibitor or exogenous BDNF into the dorsal hippocampus. Behavioral experiments were performed by open field and fear conditioning tests (FCTs). Western blotting was also used to measure the expression levels of BDNF, proBDNF, TrkB, p-TrkB, p75NTR, and synapse proteins. Golgi staining and electrophysiology were applied to evaluate the neuronal synaptic plasticity. Here, we demonstrated that anesthesia/surgery induced a reduction of BDNF/proBDNF, which negatively regulates the synaptic function in hippocampus, subsequently leading to cognitive impairment in aged mice. P75NTR inhibitor and exogenous BDNF could attenuate cognitive deficits by rescuing the dendritic spine loss and long-term potentiation (LTP) via altering the BDNF/proBDNF ratio. This study unveiled that the BDNF/proBDNF ratio in the hippocampus played a key role in anesthesia-/surgery-induced POCD. Thereby, tuning the ratio of BDNF/proBDNF is supposed to be a promising therapeutic target for POCD.

Background Intravenous and inhalational agents are commonly used in general anesthesia. However, it is still controversial which technique is superior for the quality of postoperative recovery. This meta-analysis aimed at comparing impact of total intravenous anesthesia (TIVA) versus inhalational maintenance of anesthesia on the quality of recovery in patients undergoing non-cardiac surgery. Methods We systematically searched EMBASE, PubMed, and Cochrane library for randomized controlled trials (RCTs), with no language or publication status restriction. Two authors independently performed data extraction and assessed risk of bias. The outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) based on a random-effect model. We performed trial sequential analysis (TSA) for total QoR-40 scores and calculated the required information size (RIS) to correct the increased type I error. Results A total of 156 records were identified, and 9 RCTs consisting of 922 patients were reviewed and included in the meta-analysis. It revealed a significant increase in total QoR-40 score on the day of surgery with TIVA (MD, 5.91 points; 95% CI, 2.14 to 9.68 points; P = 0.002; I2 = 0.0%). The main improvement was in four dimensions, including “physical comfort”, “emotional status”, “psychological support” and “physical independence”. There was no significant difference between groups in total QoR-40 score (P = 0.120) or scores of each dimension on POD1. The TSA showed that the estimated required information size for total QoR-40 scores was not surpassed by recovered evidence in our meta-analysis. And the adjusted Z-curves did not cross the conventional boundary and the TSA monitoring boundary. Conclusion Low-certainty evidence suggests that propofol-based TIVA may improve the QoR-40 score on the day of surgery. But more evidence is needed for a firm conclusion and clinical significance.

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