GSDMD-mediated NETosis promotes the development of acute respiratory distress syndrome.

Gasdermin D (GSDMD) is a classical molecule involved in pyroptosis. It has been reported to be cleaved into N-terminal fragments to form pores in the neutrophil membrane and promote the release of neutrophil extracellular traps (NETs). However, it remains unclear if GSDMD is involved in neutrophil regulation and NET release during ARDS. The role of neutrophil GSDMD in the development of ARDS was investigated in a murine model of ARDS induced by lipopolysaccharide (LPS) using the neutrophil specific GSDMD-deficient mice. The neutrophil GSDMD cleavage and its relationship with NETosis were also explored in ARDS patients. The cleavage of GSDMD in neutrophils from ARDS patients and mice was upregulated. Inhibition of GSDMD by genetic knockout or inhibitors resulted in reduced production of NET both in vivo and in vitro, and attenuation of LPS-induced lung injury. Moreover, in vitro experiments showed that the inhibition of GSDMD attenuated endothelial injury co-cultured with neutrophils from ARDS patients, while extrinsic NETs reversed the protective effect of GSDMD inhibition. Collectively, our data suggest that the neutrophil GSDMD cleavage is crucial in NET release during ARDS. The NET release maintained by cleaved GSDMD in neutrophils may be a key event in the development of ARDS.

Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental mouse model of sepsis.

PD-L1 is a ligand for PD-1, and its expression has been shown to be upregulated in neutrophils harvested from septic patients. However, the effect of PD-L1 on neutrophil survival and sepsis-induced lung injury remains largely unknown. In this study, PD-L1 expression correlated negatively with rates of apoptosis in human neutrophils harvested from patients with sepsis. Coimmunoprecipitation assays on control neutrophils challenged with interferon-γ and LPS showed that PD-L1 complexes with the p85 subunit of phosphatidyl 3-kinase (PI3K) to activate AKT-dependent survival signaling. Conditional CRE/LoxP deletion of neutrophil PD-L1 in vivo further protected against lung injury and reduced neutrophil lung infiltration in a cecal ligation and puncture (CLP) experimental sepsis animal model. Compared with wild-type animals, PD-L1-deficient animals presented lower levels of plasma tumor necrosis factor-α and interleukin-6 (IL-6) and higher levels of IL-10 after CLP, and reduced 7-day mortality in CLP PD-L1-knockout animals. Taken together, our data suggest that increased PD-L1 expression on human neutrophils delays cellular apoptosis by triggering PI3K-dependent AKT phosphorylation to drive lung injury and increase mortality during clinical and experimental sepsis.

Histone methyltransferase SETD2 inhibits M1 macrophage polarization and glycolysis by suppressing HIF-1α in sepsis-induced acute lung injury.

Sepsis is a severe syndrome caused by the imbalance of the host response to infection, accompanied by multiple organ damage, especially acute lung injury. SET Domain-Containing 2 (SETD2) is a methyltransferase catalyzing H3 lysine 36 trimethylation (H3K36me3) that regulates multiple biological processes. This study focused on explicating the action of SETD2 on macrophage function in sepsis and the precise mechanism involved. Enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting were used to determine expression. Luciferase reporter assay and chromatin immunoprecipitation assay were conducted to detect the binding of SETD2 or H3K36me3 with the hypoxia-inducible factor 1, alpha subunit (Hif1a) gene. A sepsis-induced acute lung injury model was constructed via cecal ligation and puncture (CLP). SETD2 was decreased in RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Besides, SETD2 suppressed M1 macrophage polarization and glycolysis caused by LPS. HIF-1α was enhanced in RAW 264.7 cells stimulated by LPS and inversely related to SETD2 expression. In addition, SETD2-catalyzed H3K36me3 bound to the Hif1a gene to modulate HIF-1α expression. Furthermore, Hif1a silencing suppressed Setd2 silencing-induced M1 macrophage polarization and glycolysis in RAW 264.7 cells. Moreover, overexpression of Setd2 inhibited CLP-induced lung injury and M1 macrophage polarization in mice. SETD2 suppressed M1 macrophage polarization and glycolysis via regulating HIF-1α through catalyzing H3K36me3 in sepsis.

Nicotinamide Mononucleotide Attenuates LPS-Induced Acute Lung Injury With Anti-Inflammatory, Anti-Oxidative and Anti-Apoptotic Effects.

INTRODUCTION: Nicotinamide mononucleotide (NMN) is a nucleotide that is commonly recognized for its role as an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis with multiple pharmacological effects. The purpose of this study was to evaluate the protective effect of nicotinamide mononucleotide (NMN) against lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: We investigated the effect of NMN on ALI-induced inflammatory response, oxidative stress, and cell apoptosis. The ALI mouse model was performed by injecting LPS intratracheally at a dose of 10 mg/kg in 50 µL saline. Flow cytometry was used to detect neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and ELISA was used to detect the contents of inflammatory cytokines TNF-α, IL-1ß and IL-6 in BALF. Oxidative stress was evaluated by determining the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in lung tissue. ROS formation was analyzed by immunofluorescence. Western blotting was performed to detect apoptotic levels and p38MAPK/NF-κB phosphorylation levels in lung tissue. RESULTS: In the ALI mouse model, NMN showed a significant therapeutic effect compared to the LPS group. NMN attenuated the pathological damage and cell apoptosis in lung tissue, decreased the levels of TNF-α, IL-1ß, and IL-6 in BALF, and reduced the number of total cells and neutrophils in BALF. In addition, NMN attenuated the LPS-induced elevation of dry-to-wet ratio, MDA content, p38 MAPK and p65 NF-κB phosphorylation levels, and the SOD activity was increased by NMN treatment. CONCLUSIONS: In conclusion, the present study showed that NMN exerted a protective effect on LPS-induced ALI with anti-inflammatory, antioxidative, and antiapoptotic effects.

Goldenhar syndrome complicated with subglottic airway stenosis: a case report.

BACKGROUND: Goldenhar syndrome is a congenital disease that involves an absence or underdevelopment of structures that arise from the first and second pharyngeal arches and more or less severe extracranial anomalies. A variety of supraglottic malformations may be observed, including mandibular hypoplasia, mandibular asymmetry and micrognathia. Subglottic airway stenosis (SGS), which can cause difficulties in airway management during the perioperative period, is seldom emphasized in literature descriptions of Goldenhar syndrome, but can be clinically significant. CASE PRESENTATION: An 18-year-old female with a history of Goldenhar syndrome presented for placement of a right mandibular distractor, right retroauricular dilator, and stage I transfer of a prefabricated expanded flap under general anesthesia. During tracheal intubation, the endotracheal tube (ETT) met resistance unexpectantly when attempting to pass through the glottis. Subsequently, we attempted the procedure with a smaller size ETT but again met resistance. With fiberoptic bronchoscope, we found that the whole segment of the trachea and bilateral bronchi were obvious narrow. Given the finding of unexpected severe airway stenosis and the associated risks with proceeding with the surgery, the operation was cancelled. We removed the ETT once the patient was fully awake. CONCLUSIONS: Anesthesiologists should be aware of this clinical finding when evaluating the airway of a patient with Goldenhar syndrome. Coronal and sagittal measurements on computerized tomography (CT) and three-dimensional image reconstruction can be used to evaluate the degree of subglottic airway stenosis and measure the diameter of the trachea.

Preliminary evaluation of SaCoVLM video laryngeal mask-guided intubation in airway management for anesthetized children.

BACKGROUNDS: To preliminary evaluate the application of novel SaCoVLM video laryngeal mask -guided intubation for anesthetized children. METHODS: One hundred twenty-four children with microtia (ages 5-15 years,) who required general intubation anaesthesia, were enrolled in the study. After induction of general anesthesia,guided tracheal intubation under direct vision of the SaCoVLM was performed. Our primary outcome was first-pass success rate of guided tracheal tube placement. Secondary outcome included glottic visualization grades, the first-attempt success rate of LMA placement, the time for LMA placement and time to endotracheal intubation as well as the time for LMA removal after successful intubation, the fiberoptic grade of laryngeal view, the baseline and postinduction hemodynamic parameters were also recorded,and the incidence 24 h complications after operation. RESULTS: The first-pass success rate of guided tracheal tube placement was 91.1% (95%CI = 1.04-1.14), the status of glottic visualization was classified: grade 1 in 27cases, grade 2 in 36 cases, grade 3 in 41 cases and grade 4 in 20 cases. The first success rate of LMA placement was 92.7% (95%CI = 1.03-1.13), the time for LMA insertion was 15.7 (±9.1) s, intubation time was 30.9 (±17.6) s and withdrawl time was 24.9 (±9.3) s. The incidence of postoperative sore throat at 2 h was 29%, and 16.1% at 24 h, without dysphagia and hypoxia. CONCLUSION: The SaCoVLM video laryngeal mask-guided intubation is feasible in children, with a high success rate, could be a new promising device to guide intubation in airway management. TRIAL REGISTRATION: This study was approved by the University's Institutional Review Board and written informed consent was obtained from all subjects participating in the trial. The trial was registered prior to patient enrollment at clinicaltrials.gov (ChiCTR2200061481, http://www.chictr.org.cn . Principal investigator: Juan Zhi; Date of registration: 26/06/2022.

Intubation using video laryngeal mask airway SaCoVLM and laryngeal mask airway Ambu® Aura-i in anesthetized children with microtia: a randomized controlled study.

The Ambu Aura-i laryngeal mask is considered to be a device for blind intubation as well as for fiberoptic guided intubation. The novel video laryngeal airway mask SaCoVLM is a supraglottic airway device that allows intubation under direct vision. We hypothesized that success rates for device placement and tracheal intubation with the SaCoVLM would be comparable with the Ambu Aura-i mask. A prospective, randomized clinical trial was conducted from March 2021 to December 2021. One hundred and twenty patients were enrolled and randomized in the study. Direct intubation was performed with the SaCoVLM, and fiberoptic guided intubation was performed with the Ambu Aura-i mask. The primary outcome measure was the first success rate of LMA placement. Secondary outcome measures were the time from device placement and time from endotracheal intubation (as well as the time for LMA removal after successful intubation), differences in airway leak pressure, fiberoptic grade of the laryngeal view, and incidence of blood staining. The first success rate of LMA placement was similar for the two devices. There was no difference in the time for successful endotracheal intubation between the Ambu Aura-i and SaCoVLM groups (24.1 s ± 6.3 versus 25.7 s ± 2.1; p > 0.05). The time for removal was slower in the SaCoVLM group than in the Ambu Aura-i group (20.8 s ± 0.8 versus 14.7 s ± 6.1; p < 0.01). The airway leak pressure was higher in the SaCoVLM group than in the Ambu Aura-i group (27.0 s ± 1.0 versus 22.3 s ± 3.6; p < 0.01), and the incidence of blood staining was higher in the SaCoVLM group (16.7%). The SaCoVLM has an overall comparable performance to the Ambu Aura-i mask. However, the SaCoVLM is better relative to direct intubation without the assistance of a flexible intubation scope, which reduces the device's demand.

Post-cardiopulmonary bypass hypoxaemia in paediatric patients undergoing congenital heart disease surgery: risk factors, features, and postoperative pulmonary complications.

BACKGROUND: Hypoxemia after cardiopulmonary bypass (CPB) is the quantifiable manifestation of pulmonary dysfunction. This retrospective study was designed to investigate the risk factors for post-cardiopulmonary bypass hypoxaemia and the features of hypoxaemia and pulmonary complications in paediatric congenital heart disease surgery involving CPB. METHODS: Data including demographics, preoperative pulmonary or cardiac parameters, and intraoperative interventions were retrospectively collected from 318 paediatric patients who underwent radical surgery with CPB for congenital heart disease. Among them, the factors that were significant by univariate analysis were screened for multivariate Cox regression. The lowest ratio of arterial oxygen tension and the inspiratory oxygen fraction (PaO2/FiO2), hypoxaemia (PaO2/FiO2 ≤ 300) insult time, duration of hypoxaemia, extubation time, and pulmonary complications were also analysed postoperatively. RESULTS: The morbidity of post-cardiopulmonary bypass hypoxaemia was 48.4% (154/318). Months (6 < months ≤ 12, 12 < months ≤ 36 and 36 < months compared with 0 ≤ months ≤ 6: HR 0.582, 95% CI 0.388-0.873; HR 0.398, 95% CI 0.251-0.632; HR 0.336, 95% CI 0.197-0.574, respectively; p < 0.01), preoperative intracardiac right-to-left shunting (HR 1.729, 95% CI 1.200-2.493, p = 0.003) and intraoperative pleural cavity entry (HR 1.582, 95% CI 1.128-2.219, p = 0.008) were identified as independent risk factors for the development of post-cardiopulmonary bypass hypoxaemia. Most hypoxaemia cases (83.8%, 129/154) occurred within 2 h, and the rate of moderate hypoxaemia (100 < PaO2/FiO2 ≤ 200) was 60.4% (93/154). CONCLUSION: The morbidity of post-cardiopulmonary bypass hypoxaemia in paediatric congenital heart disease surgery was considerably high. Most hypoxaemia cases were moderate and occurred in the early period after CPB. Scrupulous management should be employed for younger infants or children with preoperative intracardiac right-to-left shunting or intraoperative pleural cavity entry.

Therapeutic Effect of an Anti-Human Programmed Death-Ligand 1 (PD-L1) Nanobody on Polymicrobial Sepsis in Humanized Mice.

BACKGROUND Immunosuppression is regarded as the main cause of death induced by sepsis. Anti-programmed death-ligand 1 (PD-L1) therapy is promising in reversing sepsis-induced immunosuppression but no evidence is available on use of commercially available anti-PD-L1 medications for this indication. The present preclinical study was performed to investigate the therapeutic effect of an anti-PD-L1 nanobody (KN035) in sepsis. MATERIAL AND METHODS The level of expression of PD-L1 in PD-L1 humanized mice was confirmed with flow cytometry. Plasma concentrations of KN035 at different dosages at different time points were detected using an enzyme-linked immunosorbent assay. PD-L1 humanized mice were allocated into 4 groups: sham, cecal ligation and puncture (CLP), isotype (isotype+CLP), and PD-L1 (KN035+CLP). The 7-day survival rate was observed to investigate outcomes in CLP mice. Disease severity was assessed with histopathological scoring of mice lungs and livers. Immune status was assessed based on cell apoptosis in the spleen and bacterial clearance. RESULTS PD-L1 levels were significantly elevated in peripheral lymphocytes, monocytes, and neutrophils after CLP surgery. Blood concentrations of KN035 showed that 2.5 mg/kg had potential to be an ideal dosage for KN035 therapy. Survival analysis demonstrated that KN035 was associated with significantly reduced mortality on Day 7 after surgery (P=0.0083). The histopathological tests showed that KN035 alleviated sepsis-induced injury in the lungs and liver. KN035 reduced the number of apoptotic cells in the spleen and almost eliminated bacterial colonies in the peritoneal lavage fluid from the CLP mice. CONCLUSIONS KN035, an anti-PD-L1 antibody, can improve the rate of survival in CLP mice and alleviate sepsis-induced apoptosis in the spleen.

Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: The role of dexmedetomidine in preventing postoperative delirium (POD) after cardiac surgery remains controversial because of several recent trials with negative results. We aimed to perform an updated meta-analysis of randomized controlled trials (RCTs) to clarify this controversy. METHODS: RCTs investigating the perioperative administration of dexmedetomidine in cardiac surgery were retrieved from PubMed, Web of Science, and the Cochrane library until August,27,2020. Two researchers independently screened the literature, collected the data and evaluated the bias risk of the included studies. The meta-analysis was performed with the RevMan 5.3. RESULTS: A total of 15 studies including 2813 patients were included in the study. A pooled result showed that dexmedetomidine could reduce the risk of POD in adult population underwent cardiac surgery (OR 0.56, 95%CI 0.36-0.89, P = 0.0004, I2 = 64%). The subgroup analysis demonstrated that the protective effect of dexmedetomidine was only present in the patients injected with dexmedetomidine after surgery but not from the start of surgery, in the adult patients without specific age limitation but not in the elderly, and in the studies in comparison with other sedatives but not with placebo. There were no statistical differences when analyzing the secondary outcomes including hypotension (OR 1.13; 95% CI 0.54-2.37, P < 0.00001, I2 = 85%), bradycardia (OR 1.72; 95% CI 0.84-3.53, P = 0.04, I2 = 58%) and atrial fibrillation (OR 0.87; 95% CI 0.70-1.08, P = 0.43, I2 = 0). CONCLUSIONS: Dexmedetomidine can reduce the incidence of POD compared to other sedatives and opioids after cardiac surgery in adult patients. The proper population and timing for perioperative use of dexmedetomidine after cardiac surgery remain to be further investigated.

Targeting Lymphocyte Activation Gene 3 to Reverse T-Lymphocyte Dysfunction and Improve Survival in Murine Polymicrobial Sepsis.

BACKGROUND: Lymphocyte activation gene 3 (LAG-3) is one of the immune checkpoint molecules, negatively regulating the T-cell reactions. The present study investigated the role of LAG-3 in sepsis-induced T-lymphocyte disability. METHODS: Mice sepsis was induced by cecal ligation and puncture (CLP). LAG-3 expression on some immune cells were detected 24 hours after CLP. LAG-3 knockout and anti-LAG-3 antibody were applied to investigate the effects on the survival, bacterial clearance. Cytokine levels, T-cell counts, and the presence of apoptosis (in blood, spleen, and thymus) were also determined. In vitro T-cell apoptosis, interferon γ secretion, and proliferation were measured. The expression of interleukin 2 receptor on T cells was also determined after CLP. RESULTS: LAG-3 was up-regulated on CD4+/CD8+ T, CD19+ B, natural killer, CD4+CD25+ regulatory T cells and dendritic cells. Both LAG-3 knockout and anti-LAG-3 antibody had a positive effect on survival and on blood or peritoneal bacterial clearance in mice undergoing CLP. Cytokine levels and T-cell apoptosis decreased in anti-LAG-3 antibody-treated mice. Induced T-cell apoptosis decreased, whereas interferon γ secretion and proliferation were improved by anti-LAG-3 antibody in vitro. Interleukin 2 receptor was up-regulated on T cells in both wild-type and LAG-3-knockout mice undergoing CLP. CONCLUSIONS: LAG-3 knockout or anti-LAG-3 antibody blockade protected mice undergoing CLP from sepsis-associated immunodysfunction and may be a new target for the treatment.

Three Ingredients of Safflower Alleviate Acute Lung Injury and Inhibit NET Release Induced by Lipopolysaccharide.

Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung injury in mice, which were then treated with SYA, HSYA, and AHSYB. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected to detect degree of lung injury, level of inflammation, and neutrophil extracellular traps (NETs). In vitro experiments were performed using HL-60 cells stimulated with phorbol myristate acetate (PMA). Lung injury induced by LPS was alleviated by SYA, HSYA, and AHSYB as demonstrated by the histopathologic test. The three components inhibit LPS-induced elevation of the levels of inflammatory factors and wet-to-dry weight ratio as well as the amount of protein and cells in the BALF. They also induced a remarkably less overlay of myeloperoxidase (MPO) and histone in the immunofluorescence assay and reduced level of MPO-DNA complex in plasma. The in vitro assay showed a similar trend that the three components inhibited PMA-induced NET release in neutrophil-like HL-60 cells. Western blot demonstrated that phosphorylation of c-rapidly accelerated fibrosarcoma (c-Raf), mitogen-activated protein kinase ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) in the lungs of LPS-challenged mice, and PMA-treated HL-60 cells were all significantly reduced by SYA, HSYA, and AHSYB. Therefore, our data demonstrated that three components of XBJ, including SYA, HSYA, and AHSYB, showed a protective effect against LPS-induced lung injury and NET release.

Lung protective ventilation in infants undergoing cardiopulmonary bypass surgery for congenital heart disease: A prospective randomized controlled trial.

BACKGROUND: Lung protective ventilation (LPV) has been applied to surgical adults with normal pulmonary function for optimizing mechanical ventilation and reducing postoperative pulmonary complications. Few studies have reported the use of LPV in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB). AIMS: To explore safety and effectiveness of LPV in infants undergoing CPB surgery for congenital heart disease (CHD). METHODS: Included in this study were 77 infants who underwent CPB surgery for CHD from November 2017 to September 2018. They were randomized into the LPV group and conventional ventilation (CV) group. In the LPV group, small-tidal-volume (6-8 ml/kg) ventilation, lung recruitment by PEEP increment to the maximum level of 15 cm H2 O after CPB, and individualized optimal PEEP titration were applied. In the CV group, traditional tidal volume (10-12 ml/kg with zero PEEP) was applied. The primary outcome was the ratio of arterial partial pressure of oxygen to inspiratory oxygen fraction (PaO2 /FiO2 ). The secondary outcomes were respiratory dynamic parameters, hypoxemia, prognostic indexes, and postoperative pulmonary complications. RESULTS: PaO2 /FiO2 in the LPV group (416.86, 95%CI: 381.60-452.12) was significantly higher than that in the CV group (263.37, 95%CI: 227.65-299.09) after intervention (P < .001). There was a significant difference in the trend of change in dynamic compliance, alveolar-arterial oxygen difference, arterial-end-expired carbon dioxide difference, driving pressure, and respiratory index between the two groups at different time points from weaning from CPB to 2 hours after operation. There was no significant difference in PaO2 /FiO2 , alveolar-arterial oxygen difference, respiratory index, and dynamic compliance 2 hours postoperative and in the incidence of postoperative pulmonary complications, prognostic indexes between the two groups. CONCLUSIONS: LPV could be used safely in infants undergoing CPB in that it can improve oxygenation, alveolar aeration, and dynamic compliance, and reduce driving pressure, pulmonary shunting, and dead space. Its effect on oxygenation, pulmonary gas exchange, and pulmonary compliance was relatively short, and had less impact on postoperative pulmonary complications and prognosis.

Predictive value of the surgical pleth index for the hemodynamic responses to trachea intubation and skin incision.

Surgical pleth index (SPI) has been widely investigated in assessing the nociceptive level. The aim of this study was to investigate the relationship between SPI level and patient responses to trachea intubation and skin incision. A total of 40 patients undergoing open abdominal general surgery were recruited for analyses. The patients were monitored with electrocardiogram, non-invasive blood pressure, SpO2, invasive blood pressure and SPI before anesthesia induction. Anesthesia was induced with midazolam, propofol, sufentanil and rocuronium and maintained with sufentanil and sevoflurane. Blood pressure, heart rate and SPI were recorded for analyses during the peri-intubation and peri-incision periods. A receiver operating characteristic (ROC) curve analysis was performed to analyze the predictive value of blood pressure, heart rate (HR) and SPI for hemodynamic responses for trachea intubation and skin incision. SPI had a similar changing trend to systolic blood pressure (SBP) and diastolic blood pressure (DBP). The SPI level was linearly correlated with SBP, DBP and HR. SPI increased significantly after intubation and incision in patients with positive but not negative responses to intubation and incision. The ROC analysis showed that only SBP level is predictive of intubation responses. These data suggested that SPI elevated under the noxious stimulation by intubation and incision, but it was not predictive of the hemodynamic responses to intubation and incision.

[Impacts of Different Nostril for Nasotracheal Intubation with Video Laryngoscopy].

Objective To compare the impacts of different nostril on nasotracheal intubation with video laryngoscopy.Methods Totally 120 ASA grade I maxillofacial surgery patients were equally randomized into two groups:group A(left nostril)and group B(right nostril).After rapid induction of anesthesia,the nasal intubation was completed by Tosight video laryngoscope,and the success rate of the first attempt of the tube passing through the nasal cavity was recorded and compared between these two groups.In addition,time of tube through nasal cavity,time of glottis exposure,total intubation time,intubation success rate,and nasal bleeding were recorded.Results The success rate of the first attempt of tube passing through the nasal cavity was not significantly different between groups A and B(84.7% vs. 81.7%;χ 2=0.202,P=0.653).The time of tube passing through nasal cavity [(7.3±4.6)s vs.(7.5±4.1)s;t=-0.223,P=0.824] and the time of glottic exposure [(6.6±1.4)s vs.(6.7±1.4)s;t=-0.348,P=0.728] had no significant differences between two groups.The success rates of first intubation attempt were 100% in both groups.The total intubation time was(35.1±9.2)s in group A and(34.0±7.8)s in group B(t=0.663,P=0.509).Intubation-related epistaxis was found in 16 cases(27.1%)in group A and in 17 cases(28.3%)in group B(χ 2 =0.022,P=0.882).Conclusion Different nasal approaches have no effect on nasal intubation.

Effect of Intravenous Dexmedetomidine Injection(1 µg/kg)on the Intubating Conditions without Muscle Relaxants in Children after Inhalation Induction with Sevoflurane.

Objective To investigate the effect of intravenous dexmedetomidine injection(1 µg/kg)on the intubating conditions after inhalation induction with sevoflurane 8% and nitrous oxide(N2O)50% in children. Methods Totally 122 patients aged 4-10 years with an American Society of Anesthesiologists physical statusⅠ undergoing elective plastic surgery under general anesthesia were randomly divided to dexmedetomidine group(intraveneously injected with dexmedetomidine 1µg/kg)and control group(injected with normal saline)by using the random sampling table.On arrival of the operating room,anesthesia was induced with sevoflurane 8% and N2O 50% in oxygen 50%.When the patient became unconscious,the intravenous cannula 24# was inserted on the dorsum of hand.One minute later,laryngoscopy and tracheal intubation were performed.The intubating conditions were assessed by the scoring system in the previous study. Results The rates of acceptable conditions were 97% and 90% in dexmedetomidine group and in control group(P=0.143),and the rates of excellent conditions were 82% and 67%(P=0.04),respectively.In dexmedetomidine group,there were no signifi-cant differences of mean arterial presser and heart rate between the time-point of before intubation and the time-point of immediately after intubation.Conclusion Intravenous bolus of dexmedetomidine(1 µg/kg)can effectively improve the intubating conditions after inhalation induction of sevoflurane 8% and N2O 50% in children and make the hemodynamics more stable during tracheal intubation.

Target-Controlled Infusion of Propofol in Training Anesthesiology Residents in Colonoscopy Sedation: A Prospective Randomized Crossover Trial.

BACKGROUND: Propofol is widely used in sedation for colonoscopy, but its adverse effects on cardiovascular and respiratory systems are still concerning. The present study investigated whether target controlled infusion (TCI) of propofol could provide a better sedation quality than manually controlled infusion (MCI) in training inexperienced anesthesiology residents. MATERIAL/METHODS: Eighteen training residents were allocated into 2 groups receiving TCI and MCI training in their first month in the endoscopy center, while receiving MCI and TCI training instead in their second month. The last 2 patients at the end of each month were included to analyze the sedation quality of TCI and MCI techniques by comparing satisfaction of endoscopist and patients based on the visual analogue scale (VAS). Heart rate (HR), mean blood pressure (MAP), SpO2, and recovery time were also compared as the secondary outcomes. RESULTS: The demographic data were similarly distributed among the TCI and MCI patients. Endoscopist's satisfaction score in the TCI group was significantly higher than in the MCI group, 81.3±7.2 versus 74.2±9.5 (P=0.003), but the patients' satisfaction score was similar between the 2 groups. More stable hemodynamic status was obtained in the TCI group, manifested as higher lowest MAP and lower highest MAP than in the MCI group. Lowest SpO2 in the TCI group was significantly higher than in the MCI group. Patients in the TCI group recovered earlier than in the MCI group. CONCLUSIONS: TCI is a more effective and safer technique for anesthesiology residents in sedation for colonoscopy.

Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1ß Axis in Microglia.

Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1ß, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1ß. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1ß cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1ß cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1ß axis in the microglia.

Simulation-based airway management training: application and looking forward.

Within the airway management field, simulation has been used as a tool of training for over 40 years. Simulation training offers a chance of active involvement for the trainees. It can effectively enhance and upgrade the knowledge and skills of the trainees in airway management, and subsequently decrease medical errors and improve patients' outcomes and safety through a variety of airway management training modalities, such as common airway skills, difficult airway management strategies, and crisis management skills. To perform simulation-based airway management training effectively, not only are task trainers and high-fidelity simulators required but also instructors with rich experience in airway management simulation training and optimal curriculum design are essential.

Effects of Two Intranasal Dexmedetomidine Doses as Premedication on Sevoflurane EC50 for Successful Laryngeal Mask Airway Placement in Children.

Objective To observe the effects of two different intranasal dexmedetomidine doses as premedication on the EC50 of sevoflurane for successful laryngeal mask airway placement in children. Methods Children aged 3-6 years, of American Society of Anesthesiologists physical status 1, and scheduled for plastic surgery were enrolled in this study. Children were assigned to receive either spray administration of intranasal dexmedetomidine 1 µg/kg (group D1, n=21) or 2 µg/kg (group D2, n=20) approximately 30 minutes before anesthesia. Anesthesia was induced with sevoflurane up to 8% in 100% O2, with fresh gas flow set to 6 L/min. After the pupil fixed to the middle position, sevoflurane dial setting was reduced to 5% and fresh gas flow reduced to 3 L/min. The endtidal sevofluran (ETsevo) concentration for laryngeal mask airway insertion sustained for 10 minutes after vein intubation, which was determined according to the Dixon's up and down method. The initial endtidal sevoflurane concentration in each group was set at 2%. ETsevo was increased/decreased (1:1.2) in the next patient according to the response to laryngeal mask airway insertion. Bispectral index, mask acceptance, all response to laryngeal mask airway insertion, and ETsevo of laryngeal mask airway insertion of children were recorded. Results The bispectral index value was 77.4±3.6 in group D2, which was significantly lower than that (87.4±1.9) in group D1 when children entered operation room (P<0.05). Mask acceptance was 76.2% in group D1 and 90.0% in group D2. The EC50 of sevoflurane for laryngeal mask airway insertion was 1.09% (95% CI=0.89%-1.28%) in group D2, which was lower than 1.59% (95% CI=1.41%-1.78%) in group D1 (P<0.05). Conclusion Compared with the dose of 1 µg/kg, spray administration of intranasal dexmedetomidine 2 µg/kg as premedication can reduce the sevoflurane EC50 for successful laryngeal mask airway placement in children.