Background Sepsis-associated encephalopathy (SAE) is characterized by diffuse brain dysfunction, long-term cognitive impairment, and increased morbidity and mortality. The current treatment for SAE is mainly symptomatic; the lack of specific treatment options and a poor understanding of the underlying mechanism of disease are responsible for poor patient outcomes. Fgr is a member of the Src family of tyrosine kinases and is involved in the innate immune response, hematologic cancer, diet-induced obesity, and hemorrhage-induced thalamic pain. This study investigated the protection provided by an Fgr kinase inhibitor in SAE and the underlying mechanism(s) of action. Methods A cecal ligation and puncture (CLP)-induced mouse sepsis model was established. Mice were treated with or without an Fgr inhibitor and a PGC-1α inhibitor/activator. An open field test, a novel object recognition test, and an elevated plus maze were used to assess neurobehavioral changes in the mice. Western blotting and immunofluorescence were used to measure protein expression, and mRNA levels were measured using quantitative PCR (qPCR). An enzyme-linked immunosorbent assay was performed to quantify inflammatory cytokines. Mitochondrial membrane potential and morphology were measured by JC-1, electron microscopy, and the MitoTracker Deep Red probe. Oxidative stress and mitochondrial dysfunction were analyzed. In addition, the regulatory effect of Fgr on sirtuin 1 (SIRT1) was assessed. Results CLP-induced sepsis increased the expression of Fgr in the hippocampal neurons. Pharmacological inhibition of Fgr attenuated CLP-induced neuroinflammation, the survival rate, cognitive and emotional dysfunction, oxidative stress, and mitochondrial dysfunction. Moreover, Fgr interacted with SIRT1 and reduced its activity and expression. In addition, activation of SIRT1/PGC-1α promoted the protective effects of the Fgr inhibitor on CLP-induced brain dysfunction, while inactivation of SIRT1/PGC-1α counteracted the benefits of the Fgr inhibitor. Conclusions To our knowledge, this is the first report of Fgr kinase inhibition markedly ameliorating SAE through activation of the SIRT1/PGC-1α pathway, and this may be a promising therapeutic target for SAE. Graphical Abstract
Background Patients undergoing gastroenteroscopy during sedation are prone to aspiration, and most patients with dyspepsia have delayed gastric emptying. This study aimed to investigate the feasibility of measuring the gastric antrum cross-sectional area (CSA) to supply a novel clinical diagnostic reference value in patients with dyspepsia. Methods Patients with dyspepsia undergoing elective gastroscopy were included. The Perlas qualitative 0–2 grading scale score was determined before the operation. The anteroposterior diameter (D1) and craniocaudal diameter (D2) between gastric antrum serosal surfaces were measured perpendicular to each other in the supine and right lateral decubitus (RLD) positions. CSA values in the supine position and RLD position were determined. Gastric contents were endoscopically suctioned with the volumes measured and noted as actual gastric volume. Multiple regression analysis was used to fit a mathematical model for estimating the gastric volume. Receiver operating characteristic (ROC) curves were constructed to determine the accuracy of RLD CSA to detect gastric volumes of > 0.8 ml/kg. Results A total of 117 patients were enrolled and divided into a functional dyspepsia (FD) group and an organic dyspepsia group according to gastroscopy findings. For a gastric volume of > 0.8 ml/kg, cut-off values for FD and organic dyspepsia were 6.7 cm2 and 10.0 cm2, respectively. Two new modified mathematical models were derived to predict an estimated gastric volume for FD and organic dyspepsia: volume = 3.93 × RLD CSA - 0.47 × age; and volume = 6.15 × RLD CSA - 0.61 × age. Conclusion We used the cut-off value of the antral area for the fast diagnosis of gastric volumes in patients with dyspepsia, which may assist clinicians in identifying patients at risk of aspiration. Trial registration www.chictr.org.cn (CHICTR-DDD-17010871); registered 15 March 2017.
Background To compare the efficacy of anesthetic depth control using closed-loop and open-loop target controlled infusion (TCI) system of propofol guided by BIS in patients undergoing shoulder arthroscopy in the beach chair position (BCP). Methods 120 patients underwent shoulder arthroscopy surgery in the BCP were randomized into two groups, the open-loop (O) group and the closed-loop (C) group. During the maintenance phase, BIS value was used as the feedback variable for TCI system of propofol in both groups. The Global score (GS) and the percentage of adequate anesthesia, the frequency of propofol regulation, and consumption of propofol were calculated. The MMSE scores of the day before and 1 day after surgery, serum GFAP and S100B proteins before anesthesia, after extubation and 1 day after surgery were compared. Results The GS and the proportion of appropriate anesthesia time were better in the group C. The percentage of overshoot time was lower in the group C. The frequency of propofol regulation was observed higher in the group C. Propofol consumption in the group C was significantly lower than that in the group O. The MMSE scores, the GFAP and S100B protein concentrations had no significant difference between the two groups. Conclusion Propofol administration using close-loop TCI system guided by BIS may increase the percentage of adequate anesthesia and shorten the percentage of overshoot time compared with open-loop TCI model in anesthesia maintenance phase in patients undergoing shoulder arthroscopy in the BCP, and do not increase the risk of POCD.
Background To compare the efficacy of anesthetic depth control using closed-loop and open-loop target controlled infusion (TCI) system of propofol guided by BIS in patients undergoing shoulder arthroscopy in the beach chair position (BCP). Methods 120 patients underwent shoulder arthroscopy surgery in the BCP were randomized into two groups, the open-loop (O) group and the closed-loop (C) group. During the maintenance phase, BIS value was used as the feedback variable for TCI system of propofol in both groups. The Global score (GS) and the percentage of adequate anesthesia, the frequency of propofol regulation, and consumption of propofol were calculated. The MMSE scores of the day before and 1 day after surgery, serum GFAP and S100B proteins before anesthesia, after extubation and 1 day after surgery were compared. Results The GS and the proportion of appropriate anesthesia time were better in the group C. The percentage of overshoot time was lower in the group C. The frequency of propofol regulation was observed higher in the group C. Propofol consumption in the group C was significantly lower than that in the group O. The MMSE scores, the GFAP and S100B protein concentrations had no significant difference between the two groups. Conclusion Propofol administration using close-loop TCI system guided by BIS may increase the percentage of adequate anesthesia and shorten the percentage of overshoot time compared with open-loop TCI model in anesthesia maintenance phase in patients undergoing shoulder arthroscopy in the BCP, and do not increase the risk of POCD.
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