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Objective:To investigate whether propofol can cause injury to hippocampal mitochondria in neonatal rats and the regulation of excitatory amino acid receptor AMPA receptor.Methods:Forty-eight Sprague-Dawley (SD) rats aged 7 days were randomly divided into control group, propofol group, propofol+AMPA receptor agonist AMPA group (propofol+AMPA group) and propofol+AMPA receptor inhibitor CNQX group (propofol+CNQX group), with 12 rats in each group. The rats in the propofol groups were intraperitoneally injected with 30 mg/kg propofol, while in control group with 3 mg/kg normal saline. Each group was given 1/2 of the first dose every 20 minutes after the first administration, three times a day, for three consecutive days. The rats in the propofol+AMPA group and the propofol+CNQX group were injected with 1 g/L AMPA or CNQX 5 μL through left ventricle after the first administration. Three days after administration, the rats were sacrificed to obtain brain tissue. Western blotting was used to determine the expression of AMPA receptor glutamate receptors (GluR1, GluR2) subunit totally (T) and on membrane (M) in hippocampus. The expression of dynamin-related protein-1 (DRP-1) and phosphorylated-DRP-1 (p-DRP-1) and mitofusin 2 (Mfn2) related to mitochondrial fission and fusion were determined. The adenosine triphosphate (ATP) content and ATPase activity were determined.Results:Compared with the control group, GluR1 expression and its M/T ratio were significantly increased after treatment of propofol, GluR2 expression and its M/T ratio were significantly decreased, the ATP content and ATP-related enzyme activity were decreased significantly, while the expression of DRP-1 and its phosphorylation was significantly increased, and the expression of Mfn2 was significantly decreased. The changes indicated that repeated intraperitoneal injection of 30 mg/kg propofol leading to the injury of mitochondria in neural cells. Compared with the propofol group, the GluR1 expression and its M/T ratio further increased after AMPA agonist administration [T-GluR1 protein (T-GluR1/β-actin): 2.41±0.29 vs. 1.72±0.11, M-GluR1 protein (M-GluR1/β-actin): 1.18±0.15 vs. 0.79±0.09, M/T ratio: 0.78±0.12 vs. 0.46±0.08, all P < 0.01], GluR2 expression was significantly increased [T-GluR2 protein (T-GluR2/β-actin): 0.65±0.13 vs. 0.30±0.14, P < 0.01; M-GluR2 protein (M-GluR2/β-actin): 0.17±0.05 vs. 0.13±0.07, P > 0.05], but its M/T ratio was further decreased (0.27±0.10 vs. 0.41±0.08, P < 0.05). The ATP-related enzyme activity was further decreased, and the ATP content was further decreased (μmol/g: 0.32±0.07 vs. 0.70±0.10, P < 0.01). Mitochondria DRP-1 expression and its phosphorylation were further increased [DRP-1 protein (DRP-1/GAPDH): 2.75±0.36 vs. 1.70±0.19, p-DRP-1 protein (p-DRP-1/GAPDH): 0.99±0.14 vs. 0.76±0.15, both P < 0.05], and Mfn2 expression was further decreased (Mfn2/GAPDH: 0.23±0.12 vs. 0.54±0.12, P < 0.05). This indicated that the AMPA agonist increased the expression of the AMPA receptor GluR1 subunit on the cell membrane and shifted the GluR2 into the cell, thus increasing the mitochondrial injury caused by propofol. Compared with the propofol group, the GluR1 expression and its M/T ratio decreased significantly after AMPA inhibitor administration [T-GluR1 protein (T-GluR1/β-actin): 0.99±0.14 vs. 1.72±0.11, M-GluR1 protein (M-GluR1/β-actin): 0.21±0.07 vs. 0.79±0.09, M/T ratio: 0.21±0.07 vs. 0.46±0.08, all P < 0.01], the change of GluR2 expression was not significant, but its M/T ratio was significantly increased (0.59±0.09 vs. 0.41±0.08, P < 0.05). The ATP-related enzyme activity was increased significantly, and the ATP content was increased significantly (μmol/g: 0.87±0.12 vs. 0.70±0.10, P < 0.05). Mitochondria DRP-1 expression and its phosphorylation were significantly decreased [DRP-1 protein (DRP-1/GAPDH): 1.18±0.17 vs. 1.70±0.19, p-DRP-1 protein (p-DRP-1/GAPDH): 0.37±0.10 vs. 0.76±0.10, both P < 0.05], and Mfn2 expression was significantly increased (Mfn2/GAPDH: 0.78±0.10 vs. 0.54±0.12, P < 0.05). This indicated that AMPA inhibitor promoted the movement to the cell membrane of GluR2 subunits meanwhile inhibited the expression of GluR1 subunits, thus alleviating the injury of mitochondrial caused by propofol in the brain. Conclusions:Repeated intraperitoneal injection of 30 mg/kg propofol for 3 days can increase the expression of GluR1 subunits of AMPA receptor in 7-day neonatal rats hippocampus mainly distributing in the cell membrane, decrease the expression of GluR2 subunits moving into the cell, thus causing injury of mitochondrial function and dynamics, which can be aggravated by AMPA receptor agonist and alleviated by AMPA receptor inhibitors.
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Objective:To evaluate the effect of gender on anesthetic potency of ciprofol for gastroscopy when combined with fentanyl.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-50 yr, with body mass index of 18-25 kg/m 2, undergoing elective gastroscopy with intravenous anesthesia, were divided into 2 groups according to gender: male group (M group) and female group (F group). After fentanyl 1.5 μg/kg was intravenously injected, ciprofol was given by the Dixon′s up-and-down method, with the initial dose of 0.4 mg/kg followed by dose increment/decrement of 0.04 mg/kg. The ED 50 and 95% confidence interval of ciprofol for gastroscopy anesthesia were calculated by the probit regression analysis. Results:The ED 50 (95% confidence interval) of ciprofol for gastroscopy was 0.33 (0.32-0.34) mg/kg in F group and 0.27 (0.26-0.28) mg/kg in M patients when combined with fentanyl 1.5 μg/kg. There was no significant difference between the two groups ( P>0.05). Conclusions:There is no significant gender difference in the anesthetic potency of ciprofol for gastroscopy (ED 50: female 0.33 mg/kg, male 0.27 mg/kg) when combined with fentanyl (1.5 μg/kg).
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Objective:To compare the efficacy and safety of telbivudine (LDT) and tenofovir disoproxil fumarate (TDF) treatment during the second and third trimester in pregnant women with high viral load of hepatitis B virus (HBV).Methods:Totally 506 pregnancy women with HBV infection who received antiviral therapy during the second and third trimester of pregnancy in the obstetrical clinic of The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine from January 1, 2016 to December 31, 2018 were retrospectively enrolled, and the anti-viral efficacy and safety in mothers and neonates were evaluated. Pregnancy women were divided into TDF group and LDT group according the medications. The efficacies including decline and negative rate of HBV DNA, the vertical transmission (VT) rate, the normalization rate of liver function in mothers between the two groups were compared. The safeties including birth weight of neonates, congenital deformities and the rates of preterm between the two groups were also compared. Chi-square test, independent sample t test or rank sum test were used for statistical analysis. Results:There were 239 pregnant women in the LDT group and 267 in the TDF group. The maternal HBV DNA levels before treatment in the LDT and TDF groups were (7.83±0.75) lg IU/mL and (7.82±0.66) lg IU/mL, respectively, while the maternal HBV DNA levels prior to delivery were 2.91(1.20) lg IU/mL and 2.83(1.01) lg IU/mL, respectively. The normalization rates of alanine aminotransferase (ALT) of chronic hepatitis B (CHB) pregnant women prior to delivery in TDF group and LDT group were 95.00%(38/40) and 98.18%(54/55), respectively. There were all no significant differences between the two groups ( t=0.097, U=1.040 and χ2=0.767, respectively, all P>0.05). For CHB pregnant women, the HBV DNA negative rate at one month postpartum in TDF group was 85.45%(47/55) and that in LDT group was 82.50%(33/40). The normalization rate of ALT in TDF group was 94.55%(52/55), and that in LDT group was 92.50%(37/40). There were no significant differences between the two groups ( χ2=0.152 and 0.164, respectively, P=0.697 and 0.687, respectively). The VT rates were 0(0/262) in TDF group and 0.43%(1/231) in LDT group, which had no significant difference between the two groups ( χ2=1.127, P=0.288). Two patients in LDT group who continued taking LDT 11 months postpartum switched to TDF because of HBV rt204 mutation, and no one had virus mutation in TDF group. No significant increased in creatine kinase in LDT group, and no significant abnormal calcium and phosphorus metabolism in the TDF group. The preterm rate was 7.87%(21/267) in TDF group and 4.18%(10/239) in LDT group, but there was no significant difference between the two groups ( χ2=2.970, P=0.085). However, the birth weight of neonates in TDF group ((3 204.72±490.50) g) was lower than that in LDT group ((3 374.31±467.50) g), and the difference was statistically significant ( t=3.780, P<0.01). During the course of treatment, no pregnant women discontinued treatment due to drug intolerance, and no infants presented with drug-related birth defects. Safeties for mothers and neonates were both good. Conclusions:Both LDT and TDF treatment could reduce the VT rate in pregnant women with high HBV viral load. The safety is good for both mothers and neonates. However, for CHB pregnant women who continue antiviral therapy postpartum, TDF is superior to LDT because of lower virus mutation, thus to reduce the risk of drug resistance.
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Objective:To evaluate the effects of propofol on α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptor expression in the hippocampus of neonatal rats.Methods:Eighty-four clean-grade healthy Sprague-Dawley rats of either sex, aged 7 days, weighing 14-18 g, were divided into 2 groups ( n=42 each) using a random number table method: control group (group C) and propofol group (group P). Propofol 30 mg/kg was intraperitoneally injected in group P, fat emulsion 3 mg/kg was intraperitoneally injected in group C, 1/2 of the initial dose was given at a 20 min interval, 3 times in total, for 3 consecutive days.The arterial blood samples were taken for blood gas analysis after administration on 1st day.The rats were sacrificed at 3, 7 and 28 days after the last administration of propofol, and the bilateral hippocampus was obtained for detection of the expression of AMPA receptors containing GluR1, GluR2 and GluR3 subunits in total and membrane protein (by Western blot), and the ratio of membrane protein to total protein (M/T) was calculated.The concentrations of free calcium ion were measured.The learning and memory ability was evaluated by Morris water maze test on 28 days after the last administration. Results:Compared with group C, the expression of AMPA receptor containing GluR1 subunit in total and membrane protein was significantly up-regulated, M/T was increased, the expression of AMPA receptor containing GluR2 subunit in total and membrane protein was down-regulated, and M/T was decreased at each time point ( P<0.05), no significant change was found in the expression of AMPA receptor containing GluR3 subunits ( P>0.05), the concentrations of free calcium ion in hippocampal cells were increased, and the escape latency was prolonged, the number of crossing the original platform was decreased, and the time of staying at the target quadrant was shortened at 2-4 days of training in group P ( P<0.05). Conclusion:The mechanism by which propofol reduces cognitive function is related to up-regulation of the expression of AMPA receptors containing GluR1 subunit in the hippocampus and down-regulation of the expression of AMPA receptors containing GluR2 subunits, which increases the concentration of free calcium ions in nerve cells of neonatal rats.
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In order to eliminate the influence of motion artifacts, high-frequency noise and baseline drift on photoplethysmographic (PPG), and to obtain the accurate value of heart rate in motion state, this paper proposed a de-noising method of PPG signal based on normalized least mean square (NLMS) adaptive filtering combining ensemble empirical mode decomposition(EEMD). Firstly, the PPG signal containing noise is passed through an adaptive filter with a 3-axis acceleration sensor as a reference signal to filter out motion artifacts. Secondly, the PPG signal is decomposed by EEMD to obtain a series of intrinsic modal function (IMF) according to the frequency from high to low. The threshold range of the signal is judged by the permutation entropy (PE) criterion, thereby filtering out the high frequency noise and the baseline drift. The experimental results show that the Pearson correlation coefficient between the calculated heart rate of PPG signal and the standard heart rate based on electrocardiogram (ECG) signal is 0.731 and the average absolute error percentage is 6.10% under different motion states, which indicates that the method can accurately calculate the heart rate in moving state and is beneficial to the physiological monitoring under the state of human motion.
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ThevolatilecompositionsofDuchesneaindicawerestudiedbyheadspacesolid-phase microextraction ( HS-SPME ) , soxhlet extraction ( SE ) , ultrasonic assistant extraction ( UAE ) and steam distillation ( SD) coupled with gas chromatography-mass spectrometry ( GC-MS) . The experimental parameters of HS-SPME, including fiber type, extraction temperature, extraction time and desorption time were investigated. 47, 32, 16 and 16 compounds were identified by HS-SPME, SD, SE and UAE extracting methods, respectively. 66 compounds were obtained in total, among which 47 compounds were first reported in Duchesnea indica. The experimental results showed that terpenoids were the most abundant compositions in HS-SPME and SD, but acids accounted for 61. 44% and 69. 54% of the total content obtained by SE and UAE.
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Objective To evaluate the role of phosphatidyl-inositol 3 kinase (PI3K)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit glutamate receptor 2 (GluR2) pathway in propofol postconditioning-induced reduction of cerebral ischemia-reperfusion (I/R) injury in rats.Methods One hundred and eighty male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 5 groups with 36 rats in each group:sham operation group (group S),I/R group,propofol postconditioning group (group P),intralipid postconditioning group (group Ⅰ),and PI3K inhibitor wortmannin + propofol postconditioning group (group W +P).The rats were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.Cerebral I/R was produced by 60 min middle cerebral artery occlusion followed by reperfusion.Propofol and 10% intralipid were infused via the femoral vein at a rate of 20 mg· kg-1· h-1 for 2 h starting from the onset of reperfusion in groups P and I,respectively,while the equal volume of normal saline was given instead in groups I/R and S.Wortmannin 0.6 mg/kg was injected intraperitoneally at 30 min before reperfusion in group W + P.The modified Neurological Severity Score (mNSS) was assessed and the cerebral infarct volume was detected at 12 and 24 h after operation.The hippocampi on the ischemic side were obtained at 4,6,12 and 24 h after operation for determination of expression of PI3KGluR2-containing AMPA receptor (by co-immunoprecipitation and Western blot) and activity of PI3K (by ELISA).Results Compared with group S,the mNSSs and infarct volume were significantly increased at 12 and 24 h after operation,and the activity of PI3K was decreased,and the expression of PI3K-GluR2-containing AMPA receptor was down-regulated at 4,6,12 and 24 h after operation in the other four groups (P ＜ 0.05).Compared with group I/R,the mNSSs and infarct volume were significantly decreased at 12 and 24 h after operation,and the activity of PI3K was increased,and the expression of PI3K-GluR2-containing AMPA receptor was up-regulated at 4,6,12 and 24 h after operation in group P (P ＜ 0.05).Compared with group W + P,no significant change was found in the parameters mentioned above in groups I/R and I (P ＞ 0.05),and the mNSSs and infarct volume were significantly decreased at 12 and 24 h after operation,and the activity of PI3K was increased,and the expression of PI3K-GluR2-containing AMPA receptor was up-regulated at 4,6,12 and 24 h after operation in group P (P ＜0.05).Conclusion PI3K-AMPA receptor subunit GluR2 pathway is involved in propofol postconditioning-induced reduction of cerebral I/R injury in rats.
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Objective To evaluate the role of Akt-glycogen synthase kinase-3 beta (GSK3β) signaling pathway in the long-term neuroprotection induced by propofol postconditioning in a rat model of focal cerebral ischemia/reperfusion (I/R) injury.Methods Two hundred and sixteen male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 4 groups (n =54 each):sham operation group (group S),I/R group,intralipid control group (group I) and propofol postconditioning group (group P).The model of focal cerebral I/R injury was established by middle cerebral artery occlusion.Propofol 20 mg·kg-1 · h-1 was infused over 2 h starting from the onset of reperfusion in group P,the equal volume of normal saline was given in groups S and I/R and the equal volume of 10％ intralipid was given in group I.Six rats were chosen at 3,7,14 and 28 days after occlusion and sacrificed,and brains were removed for determination of the cerebral infarct size by TTC staining.Another 6 rats were chosen at 3,7,14 and 28 days after occlusion to detect the expression of Akt,GSK3β and phosphorylation of Akt and GSK3β by Western blot.The left 6 rats were chosen at 28 day after occlusion to measure the number of newly generated neurons in hippocampal dentate gyms on the ischemic side.Results Compared with group S,the cerebral infarct volume was significantly enlarged,the newly generated neurons number was increased in the other 3 groups,and the phosphorylation of Akt and GSK3β was decreased in groups I/R and I,while increased in group P (P ＜ 0.05).The cerebral infarct volume was significantly smaller,and the newly generated neurons number and phosphorylation of Akt and GSK3β were higher in group P than in group I/R (P ＜ 0.05).Conclusion The mechanism by which propofol postconditioning provides the long-term neuroprotection is related to Akt-GSK3β signaling pathway in a rat model of focal cerebral I/R injury.