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The present study aimed to investigate cognitive dysfunction in the hippocampus induced by sepsis-associated encephalopathy (SAE) via acetylation of cyclophilin D (CypD) and opening of mitochondrial permeability transition pore. It also explored whether activating sirtuin 3 (SIRT3) can mediate deacetylation of CypD and prevent the development of SAE. Male mice were randomly assigned to six groups: sham group, cecal ligation puncture group, CypD siRNA transfection (CypD-si) group, CypD control siRNA transfection (CypD-c) group, SIRT3 overexpression vector pcDNA3.1 (SIRT3-p) group, and SIRT3 empty vector pcDNA3.1 (SIRT3-v) group (n = 18). The CypD-si and CypD-c groups were transfected with CypD siRNA and CypD control siRNA, respectively. The SIRT3-p and SIRT3-v groups were injected with SIRT3 pcDNA3.1 and vector pcDNA3.1, respectively. The learning and memory function was assessed using the learning version of the Morris water maze test. Then, cell apoptosis and the levels of CypD, acetylated CypD, SIRT-3, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-3 in the hippocampus were determined. The levels of CypD and acetylation of CypD increased in the hippocampus induced by SAE. Increasing SIRT3 and decreasing CypD can attenuate cognitive impairment and neuroapoptosis, and protect the integrity of mitochondrial membrane from damage and restore the protein expressions of IL-6, TNF-α, and caspase-3. Activating SIRT3-mediated deacetylation of CypD attenuated learning and memory dysfunction induced by SAE.

BackgroundPrevious studies showed that isoflurane-induced cognitive deficits could be alleviated by dexmedetomidine in young animal subjects. In the current study, we examine whether dexmedetomidine could also alleviate isoflurane-induced cognitive deficits in senile animals.MethodsSenile male C57BL/6 mice (20 months) received dexmedetomidine (50 μg/kg, i.p.) or vehicle 30 minutes prior to isoflurane exposure (1.3% for 4 h). Cognitive function was assessed 19 days later using a 5-day testing regimen with Morris water maze. Some subjects also received pretreatment with α2 adrenoreceptor antagonist atipamezole (250 μg/kg, i.p.), JAK2 inhibitor AG490 (15 mg/kg i.p.) or STAT3 inhibitor WP1066 (40 mg/kg i.p.) 30 minutes prior to dexmedetomidine.ResultsIsoflurane exposure increased and reduced the time spent in the quadrant containing the target platform in training sessions. The number of crossings over the original target quadrant was also decreased. Dexmedotomidine attenuated such effects. Effects of dexmedotomidine were reduced by pretreatment with atipamezole, AG490 and WP1066. Increased phosphorylation of JAK2 and STAT3 in the hippocampus induced by isoflurane was augmented by dexmedetomidine. Effects of dexmedetomidine on JAK2/STAT3 phosphorylation were attenuated by atipamezole, AG490 and WP1066. Isoflurane promoted neuronal apoptosis and increased the expression of cleaved caspase-3 and BAD, and reduced Bcl-2 expression. Attenuation of such effects by dexmedotomidine was partially blocked by atipamezole, AG490 and WP1066.ConclusionDexmedetomidine could protect against isoflurane-induced spatial learning and memory impairment in senile mice by stimulating the JAK2/STAT3 signaling pathway. Such findings encourage the use of dexmedetomidine in geriatric patients receiving isoflurane anesthesia.

BackgroundThe diagnosis of sepsis associated encephalopathy (SAE) remains challenging in clinical settings because of a lack of specific biomarkers. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) can be used to aid in the diagnosis of cognition related diseases. This study investigated changes in functional activities and brain metabolites in the hippocampus in SAE rats by fMRI and 1H-MRS.Materials and methodsSepsis associated encephalopathy rats underwent cecal ligation and perforation (CLP) surgery. The Morris water maze (MWM) test was then used to evaluate cognitive function. Resting state-fMRI and 1H-MRS scanning were performed 7 and 14 days after CLP surgery to reveal spontaneous neuronal activity and metabolite changes in the hippocampus. The amplitude of low-frequency fluctuation (ALFF) was used to evaluate spontaneous neuronal activity in the hippocampus. Creatine (Cr), Myo-inositol (mI), and glutamine/glutamate (Glx) levels were measured with 1H-MRS scanning. Immunofluorescence and levels of interleukin (IL)-1β, interleukin (IL)-6, and C-reactive protein (CRP) in the hippocampus were additionally detected to evaluate microglial mediated inflammatory responses. Statistical analysis was performed to evaluate correlations between hippocampal metabolism and behavioral findings.ResultsCecal ligation and perforation treated rats exhibited impaired learning and memory function in the MWM test at days 7 and 14. Elevation of IL-1β in the hippocampus, as well as immunofluorescence results, confirmed severe neuro inflammation in the hippocampus in SAE rats. Compared with the sham group, the ALFF of the right CA-1 area of the hippocampus was higher at day 7after CLP surgery. The Glx/Cr and mI/Cr ratios were enhanced at day 7 after CLP surgery and slightly lower at day 14 after CLP surgery. The ALFF value, and Glx/Cr and mI/Cr ratios were negatively correlated with time spent in the target quadrant in the MWM test.ConclusionSpontaneous neuronal activity and metabolites showed significant alterations in SAE rats. The elevated ALFF value, Glx/Cr ratio, and mI/Cr ratio in the hippocampus were positively associated with cognitive deficits. Changes in ALFF and metabolites in hippocampus may serve as potential neuroimaging biomarkers of cognitive disorders in patients with SAE.

Background In this study, we aimed to compare the effectiveness of transnasal humidified rapid insufflation ventilator exchange (THRIVE) with facemask pre-oxygenation in 40 patients ≥65 years of age undergoing general anesthesia during gastrointestinal surgery for intestinal obstruction. Material/Methods Patients with gastrointestinal obstruction were randomized to either a facemask group (group M, n=20) or THRIVE group (group T, n=20). During pre-oxygenation, the 2 groups used a facemask (100% oxygen, 6 L/min) and THRIVE (100% oxygen, 40 L/min) to supply oxygen, respectively. Induction of anesthesia was performed in both groups using facemasks and without mechanical or assisted ventilation. The intubation occurred after myorelaxant action began. When the peripheral oxygen saturation (SpO 2 ) dropped below 95%, or 480 s after administration of muscle relaxants, mechanical ventilation was initiated immediately. The primary outcome was arterial partial pressure of oxygen (PaO 2 ) at 5 min after pre-oxygenation. A secondary outcome was time to SpO 2 of 95% during apnea, with a cut-off time of 480 s. Results PaO 2 at 5 min after pre-oxygenation was (261.5±30.9) mmHg for group M and (446.1±84.4) mmHg for group T ( P <0.001). Based on survival analysis, the median time-to-event in group T was 480 s (95% CI 415.7 s – upper limit unknown) and 240 s (95% CI 225.9–254.1 s) in group M ( P <0.001). Conclusions In elderly patients undergoing rapid sequence induction, pre-oxygenation with THRIVE could improve oxygenation and extend safe apnea time, compared with facemask pre-oxygenation.

Background Despite evidence that high-flow nasal cannula oxygen therapy (HFNC) promotes oxygenation, its application in sedated gastroscopy in elderly patients has received little attention. This study investigated the effect of different inhaled oxygen concentrations (FiO2) of HFNC during sedated gastroscopy in elderly patients. Methods In a prospective randomized single-blinded study, 369 outpatients undergoing regular gastroscopy with propofol sedation delivered by an anesthesiologist were randomly divided into three groups (n = 123): nasal cannula oxygen group (Group C), 100% FiO2 of HFNC group (Group H100), and 50% FiO2 of HFNC (Group H50). The primary endpoint in this study was the incidence of hypoxia events with pulse oxygen saturation (SpO2) ≤ 92%. The secondary endpoints included the incidence of other varying degrees of hypoxia and adverse events associated with ventilation and hypoxia. Results The incidence of hypoxia, paradoxical response, choking, jaw lift, and mask ventilation was lower in both Group H100 and Group H50 than in Group C (P < 0.05). Compared with Group H100, Group H50 showed no significant differences in the incidence of hypoxia, jaw lift and mask ventilation, paradoxical response, or choking (P > 0.05). No patients were mechanically ventilated with endotracheal intubation or found to have complications from HFNC. Conclusion HFNC prevented hypoxia during gastroscopy with propofol in elderly patients, and there was no significant difference in the incidence of hypoxia when FiO2 was 50% or 100%. Trial registration This single-blind, prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20201102-04) and registered in the China Clinical Trial Center (20/10/2021, ChiCTR2100052144) before patients enrollment. All patients signed an informed consent form.

Mitochondrial dysfunction is involved in the process of sepsis and leads to the accumulation of reactive oxygen species (ROS), which breaks cellular homeostasis and activates the downstream inflammatory cascade. The autophagic removal of ROS is a well-established cellular adaptive mechanism. Adiponectin is an adipocytokine that plays an important role in metabolic and inflammatory regulation. In this study, we investigated the anti-inflammatory effect of adiponectin in a sepsis model and its potential association with autophagy. We induced RAW 264.7 macrophages with lipopolysaccharide (LPS) to set up the sepsis model and treated them with adiponectin, an inhibitor of the nucleotide-binding domain and leucine-rich repeat containing family pyrin domain–containing 3 (NLRP3), ROS, Complex I, and an autophagy inhibitor. Flow cytometry and western blot analysis were performed to detect the expression levels of ROS, NLRP3, interleukin-1 beta (IL-1β), microtubule-associated protein 1A/1B-light chain 3II/I (LC3II/I), and adenosine monophosphate–activated protein kinase (AMPK). Expression levels of NLRP3, IL-1β, and ROS were significantly increased following LPS induction, and adiponectin reversed this up-regulation. Meanwhile, adiponectin also enhanced the expression of LC3II/I, an autophagosome marker, but an autophagy inhibitor and AMPK inhibitor depleted (reversed) the anti-inflammatory and antioxidant effect of adiponectin. Taken together, in the LPS-induced sepsis model, adiponectin alleviated the inflammatory reaction by reducing ROS production, possibly by enhancing autophagy via the AMPK pathway. The activation of autophagy may therefore be a key mechanism by which adiponectin ameliorates the inflammatory reactions of sepsis.

Objective: To compare the effect of THRIVE with face mask ventilation on oxygenation and safe apneic duration after induction of general anesthesia in elderly minimally-toothed patients. Method:Single university-affiliated hospital, conducted from October 2021 to December 2021. Totally 50 patients aged ≥ 65 years with ≥ 10 missing teeth, American Society of Anesthesiology physical status I-III, Mallampati class I-II, who underwent elective surgery under general anesthesia with tracheal intubation, were randomly enrolled and assigned to a facemask group (Group M) and a THRIVE group (Group T) with a random number table. Patients in Group M were pre-oxygenated with a facemask (100% oxygen at a flow rate of 6 L/min). In Group T, patients with their mouths closed were pre-oxygenated via THRIVE (100% oxygen at a flow rate of 30 L/min). After anesthesia induction, patients in Group M were ventilated with pressure-controlled ventilation, and then the facemask was removed to stop the mask ventilation. In Group T, the patient’s mouth was kept closed, and the flow rate was adjusted to 70 L/min. Then, THRIVE was continued with an open mouth. When the safe apneic duration lasted up to 8 minutes or SpO2 decreased to 95%, observation was ended, and the patient was immediately intubated with a video laryngoscope. Tracheal intubation was successfully performed on the first attempt. The safe apneic time (SAT) (from 4 min after muscle relaxant administration to the time until SpO2 dropped to 95%) was measured. Result: Fifty patients were included in the trail. Group T patients had a significantly longer SAT compared to Group M (P=0.000). All 25 patients in Group T reached 8 minutes with their SpO2 maintained at >95%. In Group M, 6 patients (24%) maintained their SpO2 at >95% for 8 minutes. Conclusion: THRIVE, compared with facemask ventilation, can significantly increase the safe apneic duration, improve oxygenation, and shorten the reoxygenation time in elderly minimally-toothed patients during the induction of general anesthesia, which contributes to stable hemodynamics and safe tracheal intubation.