Understanding the Neural Mechanisms of General Anesthesia from Interaction with Sleep-Wake State: A Decade of Discovery.

The development of cutting-edge techniques to study specific brain regions and neural circuits that regulate sleep-wake brain states and general anesthesia (GA), has increased our understanding of these states that exhibit similar neurophysiologic traits. This review summarizes current knowledge focusing on cell subtypes and neural circuits that control wakefulness, rapid eye movement (REM) sleep, non-REM sleep, and GA. We also review novel insights into their interactions and raise unresolved questions and challenges in this field. Comparisons of the overlapping neural substrates of sleep-wake and GA regulation will help us to understand sleep-wake transitions and how anesthetics cause reversible loss of consciousness. SIGNIFICANCE STATEMENT: General anesthesia (GA), sharing numerous neurophysiologic traits with the process of natural sleep, is administered to millions of surgical patients annually. In the past decade, studies exploring the neural mechanisms underlying sleep-wake and GA have advanced our understanding of their interactions and how anesthetics cause reversible loss of consciousness. Pharmacotherapies targeting the neural substrates associated with sleep-wake and GA regulations have significance for clinical practice in GA and sleep medicine.

Activation of amygdala prokineticin receptor 2 neurons drives the anorexigenic activity of the neuropeptide PK2.

Energy homeostasis is a complex system involving multiple hormones, neuropeptides, and receptors. Prokineticins (PK1 and PK2) are agonists to two G protein-coupled receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2), which decrease food intake when injected in rodents. The relative contribution of PKR1 and PKR2 to the anorexigenic effect of PK2 and their site of action in the brain have not yet been elucidated. While PKR1 and PKR2 are both expressed in the hypothalamus, a central region involved in the control of energy homeostasis, PKR2 is also present in the amygdala, which has recently been shown to regulate food intake in response to several anorexigenic signals. PKR trafficking and signaling are inhibited by the melanocortin receptor accessory protein 2 (MRAP2), thus suggesting that MRAP2 has the potential to alter the anorexigenic activity of PK2 in vivo. In this study, we investigated the importance of PKR1 and PKR2 for PK2-mediated inhibition of food intake, the brain region involved in this function, and the effect of MRAP2 on PK2 action in vivo. Using targeted silencing of PKR2 and chemogenetic manipulation of PKR2 neurons, we show that the anorexigenic effect of PK2 is mediated by PKR2 in the amygdala and that altering MRAP2 expression in PKR2 neurons modulates the activity of PK2. Collectively, our results provide evidence that inhibition of food intake by PKs is not mediated through activation of hypothalamic neurons but rather amygdala PKR2 neurons and further establishes the importance of MRAP2 in the regulation of energy homeostasis.

Medial Septal Glutamatergic Neurons Modulate States of Consciousness during Sevoflurane Anesthesia in Mice.

BACKGROUND: Multiple neural structures involved in maintaining wakefulness have been found to promote arousal from general anesthesia. The medial septum is a critical region that modulates arousal behavior. This study hypothesized that glutamatergic neurons in the medial septum play a crucial role in regulating states of consciousness during sevoflurane general anesthesia. METHODS: Adult male mice were used in this study. The effects of sevoflurane anesthesia on neuronal activity were determined by fiber photometry. Lesions and chemogenetic manipulations were used to study the effects of the altered activity of medial septal glutamatergic neurons on anesthesia induction, emergence, and sensitivity to sevoflurane. Optogenetic stimulation was used to observe the role of acute activation of medial septal glutamatergic neurons on cortical activity and behavioral changes during sevoflurane-induced continuous steady state of general anesthesia and burst suppression state. RESULTS: The authors found that medial septal glutamatergic neuronal activity decreased during sevoflurane anesthesia induction and recovered in the early period of emergence. Chemogenetic activation of medial septal glutamatergic neurons prolonged the induction time (mean ± SD, hM3Dq-clozapine N-oxide vs. hM3Dq-saline, 297.5 ± 60.1 s vs. 229.4 ± 29.9 s, P < 0.001, n = 11) and decreased the emergence time (53.2 ± 11.8 s vs. 77.5 ± 33.5 s, P = 0.025, n = 11). Lesions or chemogenetic inhibition of these neurons produced the opposite effects. During steady state of general anesthesia and deep anesthesia-induced burst suppression state, acute optogenetic activation of medial septal glutamatergic neurons induced cortical activation and behavioral emergence. CONCLUSIONS: The study findings reveal that activation of medial septal glutamatergic neurons has arousal-promoting effects during sevoflurane anesthesia in male mice. The activation of these neurons prolongs the induction and accelerates the emergence of anesthesia.

A naturaly attenuated largemouth bass ranavirus strain provided protection for Micropterus salmoides by immersion immunization.

Largemouth bass ranavirus (LMBV) causes disease outbreaks and high mortality at all stages of largemouth bass farming. Therefore, live vaccine development is critical for largemouth bass prevention against LMBV by immersion immunization. Herein, an attenuated LMBV strain with good immunogenicity, designated as LMBV-2007136, was screened from the natural LMBV strains bank through challenge assay and immersion immunization experiment. After determing the safe concentration range of LMBV-2007136, the minimum immunizing dose of immersion immunization was verified. When largemouth bass were vaccinated by immersion at the lowest concentration of 102.0 TCID50/mL, all of fish were survival post virulent LMBV challenge, and the relative percent survival (RPS) was 100 %. And the immune gene expression levels of IL-10, IL-12, IFN-γ, and IgM in the spleen and kidney post-vaccination were significantly up-regulated compared to the control group, but TNF-α expression showed no significant changes. The safety and efficacy of LMBV-2007136 at passages P8, P13, and P18 were futher assessed, and no death of largemouth bass was observed within 21 days post-immunization and RPS of three vaccination groups was 100 %, suggesting that the safety and efficacy of the attenuated strain at different passages was stable. Furthermore, in the virulence reversion test, the attenuated strain was propagated through 5 times in largemouth bass by intraperitoneal injection and no abnormality and mortality were observed, further proving the attenuated vaccine candidate LMBV-2007136 was safe. These results proved that LMBV-2007136 could be a promising candidate for a live vaccine to protect largemouth bass from LMBV disease.

Early Sacral Neuromodulation Prevented Detrusor Overactivity in Rats With Spinal Cord Injury.

OBJECTIVES: Sacral neuromodulation (SNM) has been shown to alleviate bladder dysfunction in patients with overactive bladder and nonobstructive urinary retention. However, the therapeutic effect and mechanism of SNM in neurogenic bladder dysfunction are still not fully understood. Using a rat model of spinal cord injury (SCI), this study aims to investigate the therapeutic effect of early SNM in the bladder-areflexia phase on neurogenic bladder dysfunction and evaluate its possible mechanism. MATERIALS AND METHODS: Basic physiological parameters such as body/bladder weight, blood pressure, and electrocardiogram results were measured to evaluate the safety of SNM. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction were used to examine the expression of proinflammatory factors. Hematoxylin and eosin and Masson's trichrome staining were used to observe morphological changes, and cystometry was used to evaluate urodynamic changes after SNM treatment. Western blotting and immunofluorescence staining were used to measure the levels of transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the L6-S1 dorsal root ganglia (DRGs) and bladder. Capsaicin desensitization was used to investigate whether inhibiting TRPV1 could prevent detrusor overactivity in SCI rats. RESULTS: Early SNM did not affect the body/bladder weight, heart rate, blood pressure, or the expression of proinflammatory cytokines (PGE2, IL-1, IL-2, IL-6, TGF-ß, or TNF-α) in the bladders of SCI rats. Morphologically, early SNM prevented urothelial edema (p = 0.0248) but did not influence collagen/smooth muscle in the bladder. Compared with untreated rats with SCI, the rats treated with SNM exhibited increased bladder capacity (p = 0.0132) and voiding efficiency (p = 0.0179), and decreased nonvoiding contraction (NVC) frequency (p = 0.0240). The maximum pressure, basal pressure, postvoid residual, and NVC amplitude did not change significantly. After the SNM treatment, the expression of TRPV1 in the bladder and CGRP in L6-S1 DRGs weredecreased (L6, p = 0.0160; S1, p = 0.0024) in SCI rats. In capsaicin-desensitized SCI rats, urodynamic results showed an increase in bladder capacity (p = 0.0116) and voiding efficiency (p = 0.0048), and diminished NVC frequency (p = 0.0116), while other parameters did not change significantly. CONCLUSIONS: Early SNM prevented urothelial edema morphologically and detrusor overactivity in SCI rats. Inhibition of TRPV1 in the bladder and DRGs may be one of the potential mechanisms for preventing detrusor overactivity by SNM.

TRIM21 of Micropterus salmoides exerts antiviral roles against largemouth bass ulcer syndrome virus.

Tripartite motif 21 (TRIM21), a member of the TRIM family, plays an important role in apoptosis, autophagy and ubiquitination in human, and has been proven to play antiviral roles in different organisms. In this study, the TRIM21 gene of Micropterus salmoides (MsTRIM21) was cloned, and it encoded 376 amino acids, which showed 89.3% similarity with Micropterus dolomieu and 38.3% with homo sapiens. Bioinformatics analysis revealed MsTRIM21 contained four domains: C4HC3-type RING-variant (RINGv), coiled coil, PRY and SPRY. The high expression level of MsTRIM21 could be detected in liver, stomach and muscle of healthy Micropterus salmoides, and it was significantly upregulated in head kidney, muscle, gill and brain and significantly down-regulated in the stomach of Micropterus salmoides infected with largemouth bass ulcer syndrome virus (LBUSV). The overexpression of MsTRIM21 could significantly inhibit the viral replication in vitro, evidenced by the reduction of CPE severity and the downregulation of the viral gene transcription. In addition, the overexpression of MsTRIM21 could significantly increase the expression level of interferon regulatory factor (IRF) 3, IRF7, myxovirus resistance 1 (Mx1), interferon stimulated gene 15 (ISG15), double-stranded RNA-activated protein kinase (PKR) and tumor necrosis factor α (TNF-α) in vitro, indicating the enhancement of innate immune response and inflammatory response, which may directly affect the replication of LBUSV. Thus, these results provide new lights on the roles of fish TRIM21 in innate immune response against iridovirus.

Selective Activation of NAc D1R-VP/LH Circuits Promotes Reanimation From Sevoflurane Anesthesia in Mice.

BACKGROUND: Emerging evidence has uncovered a vital role of nucleus accumbens (NAc) neurons that express the dopamine D1 receptor (D1R) and its upstream neural circuit in general anesthesia (GA) regulation. However, the underlying downstream neural basis of the modulation of GA emergence by NAc D1R neurons remains unknown. In the present study, we explored the downstream neural mechanism of NAc D1R neurons in the modulation of emergence from sevoflurane GA. METHODS: We traced the axonal projections of NAc D1R neurons using a cell type-specific anterograde tracing method and immunohistochemical techniques in D1R-Cre mice. Optogenetic stimulations combined with electroencephalogram/electromyogram recordings and behavioral tests were used to determine the effects of optogenetic activation of the axonal terminals of NAc D1R neurons on sevoflurane emergence during sevoflurane-induced continuous, steady-state general anesthesia (CSSGA) or burst-suppression oscillations. RESULTS: Labeled efferent fibers of NAc D1R neurons were highly distributed in the ventral pallidum (VP), lateral hypothalamus (LH), and substantia nigra pars compacta. Optogenetic activation of the NAc D1R -VP circuit during CSSGA with sevoflurane induced cortical activation (mean ± standard deviation [SD]; delta power: prestimulation versus during stimulation, 48.7% ± 5.7% vs 35.1% ± 3.3%, P < .0001; beta power: 7.1% ± 2.7% vs 14.2% ± 3.3%, P = .0264) and behavioral emergence, and restored the righting reflex in 66.7% of ChR2 mice. Optogenetic stimulation of the NAc D1R -LH circuit also produced cortical activation (delta power: prestimulation versus during stimulation, 45.0% ± 6.5% vs 36.1% ± 4.6%, P = .0016) and behavioral emergence, and restored the righting reflex in 100% of the ChR2 mice during CSSGA with sevoflurane. Under a sevoflurane-induced burst-suppression state, NAc D1R -VP/LH circuit activation produced evidence of cortical activation (burst-suppression ratio [BSR]: NAc D1R -VP circuit, prestimulation versus during stimulation, 42.4% ± 4.0% vs 26.3% ± 6.0%, P = .0120; prestimulation versus poststimulation, 42.4% ± 4.0% vs 5.9% ± 5.6%, P = .0002; BSR: NAc D1R -LH circuit, prestimulation versus during stimulation, 33.3% ± 13.4% vs 5.1% ± 4.9%, P = .0177; prestimulation vs poststimulation, 33.3% ± 13.4% vs 3.2% ± 4.0%, P = .0105) and behavioral emergence. CONCLUSIONS: Both NAc D1R -VP and NAc D1R -LH circuits are sufficient to promote reanimation from sevoflurane GA by simultaneously inducing cortical and behavioral emergence.

The effect of intraoperative transnasal humidified rapid-insufflation ventilatory exchange on emergence from general anesthesia in patients undergoing microlaryngeal surgery: a randomized controlled trial.

BACKGROUND: Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) has received extensive attention for its utility in tubeless anesthesia. Still, the effects of its carbon dioxide accumulation on emergence from anesthesia have not been reported. This randomized controlled trial aimed at exploring the impact of THRIVE combined with laryngeal mask (LM) on the quality of emergence in patients undergoing microlaryngeal surgery. METHODS: After research ethics board approval, 40 eligible patients receiving elective microlaryngeal vocal cord polypectomy were randomly allocated 1:1 to two groups, THRIVE + LM group: intraoperative apneic oxygenation using THRIVE followed by mechanical ventilation through a laryngeal mask in the post-anesthesia care unit (PACU), or MV + ETT group: mechanically ventilated through an endotracheal tube for both intraoperative and post-anesthesia periods. The primary outcome was duration of PACU stay. Other parameters reflecting quality of emergence and carbon dioxide accumulation were also recorded. RESULTS: Duration of PACU stay (22.4 ± 6.4 vs. 28.9 ± 8.8 min, p = 0.011) was shorter in the THRIVE + LM group. The incidence of cough (2/20, 10% vs. 19/20, 95%, P < 0.001) was significantly lower in the THRIVE + LM group. Peripheral arterial oxygen saturation and mean arterial pressure during intraoperative and PACU stay, Quality of Recovery Item 40 total score at one day after surgery and Voice Handicap Index-10 score at seven days after surgery were of no difference between two groups. CONCLUSIONS: The THRIVE + LM strategy could accelerate emergence from anesthesia and reduce the incidence of cough without compromising oxygenation. However, these benefits did not convert to the QoR-40 and VHI-10 scores improvement. TRIAL REGISTRATION: ChiCTR2000038652.

Improved skill for tracheal intubation using optical stylets through remote training model: a before and after interventional study.

BACKGROUND: Conducting on-site, hands-on training during the Coronavirus disease 2019 (COVID-19) pandemic has been challenging. We conducted a before and after interventional study to estimate the efficacy of a new remote hands-on training model for improving the trainees' tracheal intubation competency using optical stylets. METHODS: Residents or physicians in anesthesiology apartment who have not received the nominated training in tracheal intubation using optical stylets were enrolled. The 4-week training course contains theoretical knowledge along with preclinical and clinical training of optical stylets techniques. Competency of intubation using optical stylets on patients with normal airways was evaluated according to an assessment tool with a maximum score of 29 points based on video recording pre-post training performance. Pre-post questionnaires measured theoretical knowledge and self-efficacy. RESULTS: Twenty-two participants were included (8 females, 14 men, mean age of 33.5 years). The total score of intubation competency was significantly improved after training from 14.6±3.7 to 25.3±2.6 (P < 0.0001). The scores of three subitems (anatomical identification, hand-eye coordination, and optimized intubation condition) were all significantly increased after training (P < 0.0001). The total percentage of correct answers in the multiple-choice questionnaire increased from 58.2%±8.2% before training to 85.2%±7.2% shortly after training (P < 0.0001). In addition, the self-efficacy score was significantly increased from 2.5±1.2 to 4.4±0.6 (P < 0.0001). CONCLUSIONS: The new remote and progressively advanced hands-on training model improved the competency of intubation using optical stylets under the COVID-19 pandemic.

Interfacial Charge Transport in 1D TiO2 Based Photoelectrodes for Photoelectrochemical Water Splitting.

1D nanostructured photoelectrodes are promising for application as photoelectrochemical (PEC) devices for solar energy conversion into hydrogen (H2 ) owing to the optical, structural, and electronic advantages. Titanium dioxide (TiO2 ) is the most investigated candidate as a photoelectrode due to its good photostability, low production cost, and eco-friendliness. The obstacle for TiO2 's practical application is the inherent wide bandgap (UV-lights response), poor conductivity, and limited hole diffusion length. Here, a comprehensive review of the current research efforts toward the development of 1D TiO2 based photoelectrodes for heterogeneous PEC water splitting is provided along with a discussion of nanoarchitectures and energy band engineering influences on interfacial charge transfer and separation of 1D TiO2 composited with different dimensional photoactive materials. The key focus of this review is to understand the charge transfer processes at interfaces and the relationship between photogenerated charge separation and photoelectrochemical performance. It is anticipated that this review will afford enriched information on the rational designs of nanoarchitectures, doping, and heterojunction interfaces for 1D TiO2 based photoelectrodes to achieve highly efficient solar energy conversion.

Cobalt Chalcogenides/Cobalt Phosphides/Cobaltates with Hierarchical Nanostructures for Anode Materials of Lithium-Ion Batteries: Improving the Lithiation Environment.

Lithium-ion batteries (LIBs) are widely used in electric vehicles and portable electronic devices due to their high energy density, long cycle life, environmental friendliness, and negligible memory effect, though they also suffer from low power density, safety issues, and an aging effect. Cobalt chalcogenides/phosphides as promising anode materials have attracted intensive interests due to their high theoretical capacity based on the conversion mechanism. Cobaltates (XCo2 O4 , X = the other metal) have attracted attention because the X element can partially replace the high cost and toxic cobalt element. The serious volume variation during the cycling process has an impact, however, on the lithiation environment of above materials. Hierarchical construction can provide more active sites and shorten the diffusion pathways of Li ions as well as accommodating the volume expansion during lithiation processes. Herein, the research progress on the synthesis methods, structural characteristics, and electrochemical performances of cobalt chalcogenides/cobalt phosphides/cobaltates with hierarchical nanostructures for LIBs is presented. The concluding remarks highlight the research challenges and possible development directions of cobalt chalcogenides/cobalt phosphides/cobaltates with tailored hierarchical nanostructures for LIBs.

Surface and Interface Engineering: Molybdenum Carbide-Based Nanomaterials for Electrochemical Energy Conversion.

Molybdenum carbide (Mox C)-based nanomaterials have shown competitive performances for energy conversion applications based on their unique physicochemical properties. A large surface area and proper surface atomic configuration are essential to explore potentiality of Mox C in electrochemical applications. Although considerable efforts are made on the development of advanced Mox C-based catalysts for energy conversion with high efficiency and stability, some urgent issues, such as low electronic conductivity, low catalytic efficiency, and structural instability, have to be resolved in accordance with their application environments. Surface and interface engineering have shown bright prospects to construct highly efficient Mox C-based electrocatalysts for energy conversion including the hydrogen evolution reaction, oxygen evolution reaction, nitrogen reduction reaction, and carbon dioxide reduction reaction. In this Review, the recent progresses in terms of surface and interface engineering of Mox C-based electrocatalytic materials are summarized, including the increased number of active sites by decreasing the particle size or introducing porous or hierarchical structures and surface modification by introducing heteroatom(s), defects, carbon materials, and others electronic conductive species. Finally, the challenges and prospects for energy conversion on Mox C-based nanomaterials are discussed in terms of key performance parameters for the catalytic performance.

Integrating non-targeted metabolomics and toxicology networks to study the mechanism of Esculentoside A-induced hepatotoxicity in rats.

Esculentoside A (EsA) is a kind of triterpenoid saponins from the root tuber of Phytolacca acinosa Roxb. It has extensive medicinal activity, such as antibacterial, anti-inflammatory, immune regulation, and cell proliferation inhibition. However, some researches suggested that EsA can cause hepatotoxicity, whose mechanism is not precise. To ensure the safety and reliability in the clinical use of Phytolacca acinosa Roxb., it is necessary to establish a rapid and accurate method to evaluate the toxicity, analyze and verify the toxicity mechanism of EsA. Therefore, this research explored the mechanism of hepatotoxicity induced by EsA in rats and analyzed endogenous metabolites' changes in rat plasma by combining network toxicology with non-targeted metabolomics. We obtained 58 critical targets of EsA induced hepatotoxicity in rats based on the strategy of network toxicology, including albumin, mitogen-activated protein kinase 1, Caspase-3, etc. Many important pathways were obtained by Kyoto Encyclopedia of Genes and Genomes enrichment analysis, such as HIF-1 signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and other concerning pathways. Sixteen biomarkers, including 5-hydroxykynurenamine, N-acetylserotonin, palmitic acid, etc., were screened from rat plasma using Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS), mainly involve Glycerophospholipid metabolism, Tryptophan metabolism, and other metabolic pathways. Further analysis showed that EsA may induce liver injury by activating oxidative stress and energy metabolism disorders, triggering inflammation and apoptosis.

Lipopolysaccharide induces BV2 microglial cell migration via a decrease in SET8 expression.

Excessively activated microglia exhibit increased migration, resulting in tissue damage and chronic inflammation. Src was confirmed to play an important role in regulation of cell motility following lipopolysaccharide (LPS) treatment. SET8 plays an important part in multiple cellular signal pathways. In this study, we speculated that SET8 is involved in LPS-induced microglial migration via regulation of Src expression. Our study showed that LPS promoted cell migration via augmentation of Src expression in BV2 cells. Moreover, LPS treatment decreased SET8 expression and upregulated the expression of the transcription factor ETS proto-oncogene 1 (ETS1). Overexpression of both SET8 and small interfering ETS1 reversed LPS-induced Src expression and cell migration. The effects of short hairpin SET8 (shSET8) and ETS1 overexpression are the same as the effects of LPS treatment. Decrease of Src expression reversed the shSET8-induced and ETS1 overexpression-induced migration of BV2 cells. Furthermore, SET8 was observed to associate with ETS1. Chromatin immunoprecipitation assay indicated H4K20me1, a downstream target of SET8, in addition to ETS1, was enriched at the Src promoter region. Furthermore, shSET8 increased Src promoter activity and also increased the positive effect of ETS1 overexpression on Src promoter activity. This study shows that SET8 associates with ETS1 to regulate Src expression, which is involved in LPS-induced BV2 cell migration.

Activation of anterior thalamic reticular nucleus GABAergic neurons promotes arousal from propofol anesthesia in mice.

Propofol is widely used for the induction and maintenance of anesthesia, which causes a rapid loss of consciousness. However, the mechanisms underlying the hypnosis effect of propofol are still not fully understood. The thalamic reticular nucleus (TRN) is crucial for regulating wakefulness, sleep rhythm generation, and sleep stability, while the role of TRN in the process of propofol-induced anesthesia is still unknown. Here, we investigated the function of the anterior TRN in propofol general anesthesia. Our results demonstrated that the neural activity of anterior TRN is suppressed during propofol anesthesia, whereas it is robustly activated from anesthesia by recording the calcium signals using fiber photometry technology. The results showed that the activation of anterior TRN neurons by chemogenetic and optogenetic methods shortens the emergency time without changing the induction time. Conversely, chemogenetic or optogenetic inhibition of the TRN neurons leads to a delay in the recovery time. Our study showed that anterior TRN is crucial for behavioral arousal without affecting the induction time of propofol anesthesia.

Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan, China: lessons learnt and international expert recommendations.

Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao2 <90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao2 <90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure <90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients.

SET8 participates in lipopolysaccharide-mediated BV2 cell inflammation via modulation of TICAM-2 expression.

Microglial inflammation, involved in the occurrence and development of sepsis-associated encephalopathy, exhibits upregulation of proinflammatory cytokine and proinflammatory enzyme expression, leading to inflammation-induced neuronal cell apoptosis. TIR domain containing adaptor molecule-2 (TICAM-2) participates in lipopolysaccharide (LPS) mediated BV2 cell inflammation. SET8 plays a crucial role in a variety of cellular signal pathways. In this study, we hypothesize that SET8 participates in LPS-mediated microglial inflammation via modulation of TICAM-2 expression. Our data indicated that LPS induced BV2 inflammation via upregulation of TICAM-2 expression. Moreover, LPS treatment inhibited SET8 expression, while it increased activating transcription factor 2 (ATF2) expression. The effects of sh-SET8 and ATF2 overexpression were similar to that of LPS treatments. Inhibition of TICAM-2 expression counteracted sh-SET8-mediated and ATF2 overexpression mediated BV2 cell inflammation. Further, SET8 was found to interact with ATF2. A mechanistic study found that H4K20me1, a downstream target of SET8, and ATF2 enriched at the TICAM-2 promoter region. Luciferase reporter assays indicated that sh-SET8 increased TICAM-2 promoter activity but augmented the effect of ATF2 overexpression on TICAM-2 promoter activity as well. Co-transfection of sh-SET8 with ATF2 overexpression more dramatically increased TICAM-2 expression in BV2 cells. The present study indicated that SET8 interacted with ATF2 to modulate TICAM-2 expression, which participated in LPS-mediated BV2 cell inflammation.

Effect of dexmedetomidine on prevention of postoperative nausea and vomiting in pediatric strabismus surgery: a randomized controlled study.

BACKGROUND: Postoperative nausea and vomiting (PONV) are common side-effects following strabismus surgery. The present study aimed to compare the effects of different doses of dexmedetomidine (DEX) on PONV incidence in pediatric patients undergoing strabismus surgery. METHODS: In this prospective randomized double-blinded study, 126 pediatric patients undergoing strabismus surgery were randomized into one of three groups: Placebo group, normal saline; DEX1 group, 0.3 µg/kg dexmedetomidine, and DEX2 group, 0.5 µg/kg dexmedetomidine. Oculocardiac reflex (OCR) events were recorded during surgery. PONV or postoperative vomiting (POV) was recorded for 24 h in the ward. Pediatric anesthesia emergence delirium (PAED) scale and emergence agitation (EA) scale were recorded in the recovery room. RESULTS: Intraoperative OCR was significantly reduced in DEX2 group (42%) as compared to that of Placebo group (68%) (p = 0.0146). During the first 24 h post-op, the overall incidence of PONV was significantly lower in DEX2 group (10%) than that of Placebo group (32%) (p = 0.0142). There was no significant difference in POV among the three groups. PAED or EA scores among the three groups were similar during recovery time. CONCLUSION: Dexmedetomidine (0.5 µg/kg) reduced OCR and PONV without lengthening extubation time or recovery time in pediatric patients undergoing strabismus surgery. TRIAL REGISTRATION: The trial was prospectively registered before patient enrollment at Chinese Clinical Trial Registry (Clinical Trial Number: ChiCTR1800020176, Date: 12/19/2018).

Dexmedetomidine versus midazolam on cough and recovery quality after partial and total laryngectomy - a randomized controlled trial.

BACKGROUND: During emergence from anesthesia after partial and total laryngectomy, excessive airway reflex and systemic hypertension may lead to subcutaneous emphysema, hemorrhage or pneumothorax. METHODS: American Society of Anesthesiologist physical status III and IV male adults undergoing elective laryngectomy were recruited and randomly allocated to receive either dexmedetomidine (group D) or midazolam (group M). The primary outcome was incidence and severity of cough. Pulse oximetry results (SpO2), heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were also recorded. The visual analog scale and the Ramsay sedation scale were recorded at the points of wakefulness and departure from the post-anesthesia care unit (PACU). Rescue analgesia consumption, the time of spontaneous breath recovery, duration of the PACU stay, and the incidence of adverse effects were also recorded. RESULTS: The prevalence of no coughing was significantly higher in group D than in group M at the points of wakefulness and departure. HR, SBP, and DBP were significantly lower in group D compared with group M, and SpO2 was significantly higher in group D than in group M at the moment of laryngectomy. Pain scores were lower in group D than in group M. The Ramsay score at the point of wakefulness was higher in group D than in group M. There was no difference in time to spontaneous breathing recovery, duration of the PACU stay, and incidence of adverse effects. CONCLUSIONS: Compared with midazolam, dexmedetomidine is an effective alternative to attenuate coughing and hemodynamic changes with a low incidence of adverse events during emergence from anesthesia after partial and total laryngectomy. TRIAL REGISTRATION: NCT03918889 , registered at clinicaltrials.gov, date of registration: March 28, 2019.

Hippocampus is more vulnerable to neural damages induced by repeated sevoflurane exposure in the second trimester than other brain areas.

During the rapidly developing and sensitive period of the central nervous system (CNS), a harmful stimulus may have serious consequences. The effect of anesthetic exposure on the development of the offspring's CNS during pregnancy is still unclear and has been widely concerned. In the present study, we compared the susceptibility of the hippocampus with those of other brain regions in offsprings when the mother mice were exposed to repeated sevoflurane. We found that other than affecting motor sensation, emotion, or social behavior of offspring mice, repeated sevoflurane exposure induced significant memory deficiency. Compared with other brain regions, the hippocampus, which is the key component of the brain serving for learning and memory, was more vulnerable to repeated sevoflurane exposure. We also found that repeated sevoflurane exposure to mother mice could inhibit the axon development of hippocampal neurons. We also predicted that N6-methyladenosine modification of mRNA might play an essential role in the vulnerability of the hippocampus to sevoflurane, while the underlying cellular mechanism needs to be explored in the future. Our study may provide a new perspective for studying the mechanism of hippocampus-specific injury induced by sevoflurane exposure.