Efficacy of intraoperative subanesthetic dose of ketamine/esketamine in preventing postoperative cognitive dysfunction: a systematic review and meta-analysis.

Background: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia surgery, especially in older people, that can persist weeks or months after surgery as a short-term impairment of cognitive abilities, or even for a prolonged duration over years, potentially progressing into permanent cognitive dysfunction. However, the pathogenesis of POCD is not fully understood, and therefore an optimal solution for preventing POCD has yet to be established. Some studies have shown that intraoperative ketamine/esketamine reduces the incidence of POCD, but this remains controversial. Objectives: We evaluated the effect of intraoperative subanesthetic doses of ketamine/esketamine versus no intervention in adults undergoing general anesthesia surgery on the incidence of POCD. Data Sources: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched the PubMed, Embase, Ovid, Cochrane, Scopus, and Web of Science databases for the MeSH terms 'ketamine', 'esketamine', and 'Postoperative Cognitive Complications' from database inception to 25 June 2023. Results: We found no statistically significant difference in the incidence of POCD within 7 days for intraoperative subanesthetic dose of ketamine/esketamine compared with the control group [relative risk (RR) = 0.57, 95% confidence interval (CI): 0.32, 1.01], and the results from the subgroup analysis based on age (>60 years) also revealed that the difference was not statistically significant (RR = 0.49, 95% CI: 0.23, 1.04). Conclusion: Compared with controls, intraoperative subanesthetic dose of ketamine/esketamine has no advantage in preventing POCD in patients, or in elderly patients. This study provides reference data for POCD research and clinical drug intervention strategies. Registration: Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023401159).

Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1α/irisin/ERK1/2 signaling pathway.

Esketamine provides an immediate and noticeable antidepressant effect, although the underlying molecular processes are yet unclear. Irisin induced by aerobic exercise has been implicated in the alleviation of depressive symptoms, whether irisin expression responds to the administration of esketamine remains unknown. In this study, we found that irisin was reduced in the hippocampus and peripheral blood of chronic unpredictable mild stress (CUMS) mice, whereas the irisin level was rescued by esketamine treatment. The reduction of PGC-1α expression (transcriptional regulator of irisin gene expression) in the CUMS mice was rescued by esketamine treatment, PGC-1α knockdown significantly reduced the irisin level induced by esketamine. Additionally, FNDC5/irisin-knockout mice developed more severe depressant-like behaviors than wild-type mice under CUMS stimulation, with an attenuated the antidepressant effect of esketamine. Further research indicated that irisin-mediated modulation of esketamine on depressive-like behaviors in CUMS mice involved the ERK1/2 pathway. Overall, the PGC-1α/irisin/ERK1/2 signaling activation may be a new mechanism underlying the antidepressant activity of esketamine, denoting that irisin may be a promising therapeutic target for the treatment of depression.

Acute Effects of Intravenous Sub-Anesthetic Doses of Ketamine and Intranasal Inhaled Esketamine on Suicidal Ideation: A Systematic Review and Meta-Analysis.

Purpose: Suicide is a major public health concern with currently no validated and efficacious treatments approved. Preliminary evidence suggests that intravenous ketamine has rapid and sustained antidepressant effects, making it a candidate with therapeutic potential for depressed patients at risk for suicide. We conducted a meta-analysis to evaluate the efficacy of ketamine and esketamine in reducing suicidal ideation (SI), as well as their respective onset and duration of action. Data Sources: We searched PubMed, Embase, Ovid, Cochrane, and Web of Science databases for studies published from inception to September 29, 2022. Study Eligibility Criteria: We conducted a systematic review of all parallel randomized controlled trials (RCTs) examining the effect and duration of ketamine or esketamine on SI. Our primary outcome measure was the Suicide Scale score, which was measured using the Scale for Suicidal Ideation (SSI), Beck Scale for Suicide Ideation (BSS), Beck Depression Inventory (BDI), or Modified Scale for Suicidal Ideation (MSSI). To obtain effect sizes (Cohen's d), we calculated the difference in Suicide Scale scores before and after administration in each group. Results: Our study showed that intravenous sub-anesthetic doses of ketamine and intranasal inhaled esketamine had a significant anti-SI effect. Specifically, ketamine produced a large degree of anti-SI effect within the 4-6 hours (Cohen's d = 1.16, 95% CI: 0.50, 1.81) and a medium-large degree in the 24 hours (Cohen's d = 0.95, 95% CI: 0.48, 1.41). Esketamine, on the other hand, produced a small-medium degree of anti-SI effect within the 4-6 hours timeframe (Cohen's d = 0.26, 95% CI: 0.09, 0.44) and the 24 hours (Cohen's d = 0.30, 95% CI: 0.17, 0.47). Conclusion: Intravenous sub-anesthetic doses of ketamine and intranasal inhaled esketamine could reduce SI within 4 hours and last for 24 hours.

Plasma microRNA-221-3p as a biomarker for POCD after non-cardiac surgery.

Our previous study showed that the plasma microRNA-221-3p level could serve as a biomarker for major depression or mood. This study aimed to further investigate the role of plasma microRNA-221-3p level in postoperative cognitive dysfunction (POCD). Patients undergoing non-cardiac surgery were randomly assigned according to the inclusion and exclusion criteria. POCD was diagnosed by the Z score method. The relative level of plasma microRNA-221-3p was decided by quantitative real-time polymerase chain reaction. Multiple logistic regression analysis and receiver operating characteristic(ROC) curves were used for the analysis of plasma microRNA-221-3p prediction performance for POCD. At 7 days post-surgery, the rate of POCD was 34.04%. Patients in the POCD group had a higher preoperative depression score, older age, and longer operation duration than that in the NPOCD group. The relative level of plasma microRNA-221-3p in the POCD group was 1.78 and 2.73 times higher than that in the NPOCD group at 1 day before and 7 days after the surgery, respectively. The relative content of plasma microRNA-221-3p at 7 days after operation was an independent risk factor for POCD. The ROC curves showed that the area under the curve was 0.938 for plasma microRNA-221-3p at postoperative 7 days, and the threshold for POCD detection was 12.33 with a sensitivity and specificity of 81.3% and 96.3%, respectively. Our results indicate that the plasma postoperative microRNA-221-3p levels could be an effective predictor for POCD after non-cardiac surgery.

Combination of Capped Gold Nanoslit Array and Electrochemistry for Sensitive Aqueous Mercuric Ions Detection.

Label-free surface plasmon resonance (SPR) detection of mercuric ions in various aqueous solutions, using capped gold nanoslit arrays combined with electrochemical (EC) sensing technique, is demonstrated. The nanoslit arrays are fabricated on flexible cyclo-olefin polymer substrates by a nanoimprinting lithography method. The EC and SPR signals for the investigation of current responses and transmission SPR spectra are simultaneously measured during metal ions electrodeposition. Glycerol-water solution is studied to evaluate the resonant peak wavelength sensitivity (480.3 nm RIU-1) with a FOM of 40.0 RIU-1 and the obtained intensity sensitivity is 1819.9%. The ferrocyanide/ferricyanide redox couple performs the diffusion controlled electrochemical processes (R2 = 0.99). By investigating the SPR intensity changes and wavelength shifts of various mercuric ion concentrations, the optical properties are evaluated under chronoamperometric conditions. The sensors are evaluated in the detection range between 100 µM and 10 nM with a detection limit of 1 µM. The time dependence of SPR signals and the selectivity of 10 µM Hg2+ in the presence of 10 µM interfering metal ion species from Ca2+, Co2+, Ni2+, Na+, Cu2+, Pb2 + and Mn2+ are determined. The capped gold nanoslit arrays show the selectivity of Hg2+ and the EC sensing method is effectively utilized to aqueous Hg2+ detection. This study provides a label-free detection technique of mercuric ions and this developed system is potentially applicable to detecting chemicals and biomolecules.

Semihydrodynamic injection for high salt stacking and sweeping on microchip electrophoresis and its application for the analysis of estrogen and estrogen binding.

In this work, a semihydrodynamic (SHD) injection method was introduced and coupled with high salt stacking and electrokinetic chromatography for the analysis of estrogen and estrogen binding using a simple cross microchannel. The SHD method allows all samples to be hydrodynamically injected and focused into the separation channel at a relatively high flow rate and without splitting and diffusion, leading to reproducible bias-free injections of larger sample volumes (up to 50 nL) within 3 s. Moreover, the injection method is initiated without voltage switching, leading to a reduced mixing effect. Such advantages are well suited for performing stacking and sweeping on a microchip. We investigated the stacking effect under continuous and discontinuous co-ion conditions as well as under sweeping conditions. Micellar sweeping effect alone was relatively weak (7-8 times), partly due to a lower sodium cholate concentration (30 mM) used for the running buffer. By combining the sweeping effect with high salt stacking, however, up to a 200-300-fold enhancement factor could be achieved, and the high-salt and low-surfactant contents for the running buffer were favorable for binding study under nonequilibrium conditions. To the best of our knowledge, this is the first demonstration of the hydrodynamic injection used for high salt sample stacking on a microchip, also for further combining micellar electrochromatography and affinity separation for the analysis of hydrophobic ligand binding using microchip electrophoresis.

Microchip electrophoresis with hydrodynamic injection and waste-removing function for quantitative analysis.

Quantitative analysis is problematic for microchip electrophoresis for several reasons including chip-to-chip variation, discontinuous sample re-loading, channel reconditioning, and electrokinetic injection bias. In this study, the capability for quantitative analysis on a flow-through based microchip electrophoresis, which provides continuous sample re-loading, channel washing, reconditioning and hydrodynamic injection as well as waste removing is demonstrated to be more quantifiable and more reproducible compared to manual electrokinetic injection method. Using the flow-through microchip with waste-removing function, FITC-labeled estrogen or Rhodamine B could be continuously analyzed without significant changes (R.S.D. < 6.6%) in signal intensity for over 3 h, which is sufficient for a complete set of quantitative analysis. With the use of a phosphorylated kinase substrate as the model, a calibration curve for quantitative analysis of phosphopeptides were constructed and results indicate that both R2 value of the linearity and R.S.D. values of the peak intensity were around 0.9961 and 3.16%, respectively, without the use of an internal standard. These values were slightly improved to be around 0.9986 and 2.27%, respectively, with the use of a non-phosphopeptide counterpart as the internal standard. The potential of this flow-through device for the development of a kinase phosphorylation assay based on the quantitative method was also briefly discussed.