Objective To investigate the protective effect of mitochondrial division inhibitor 1(Mdivi-1),a mitophagy inhibitor,on cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol.Methods A total of 72 neonatal SD rats(half male and half female,aged 7 d,weighing 16.14±3.08 g)were randomly divided into 4 groups(n=18):blank control group(CON),Mdivi-1+blank control group(MCON),propofol+hypoxia group(PH),and Mdivi-1+propofol+hypoxia group(MPH).The MCON group and MPH group were pretreated with 2.4 mg/kg Mdivi-1 in 30 min in advance,and subsequently,50 mg/kg propofol was respectively given to the PH group and the MPH group.Immediately after the intraperitoneal injections were completed,the corresponding rats were transferred into a constant temperature chamber containing 18%O2.Then the rats were continuously monitored until resuming the reversing reflex and then transferred to a normoxic environment.The hypoxic treatment was carried out once per day for 7 consecutive days.Transcriptome sequencing was used to screen for differential expressed genes(DEGs),and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis was employed to conduct functional analysis.Morris water maze test was applied to exam spatial learning and memory abilities.HE staining was used to observe the morphological changes of neurons in the hippocampal CA1 region.Morphological changes of mitochondria in hippocampal neurons were observed by transmission electron microscopy(TEM).Western blotting was utilized to detect the expression of Parkin Rbr E3 ubiquitin protein ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)in the hippocampal tissues.Results KEGG analysis results indicated that the mitophagy pathway was more significantly enriched in the PH group when compared with the CON group.Morris water maze test revealed that the PH group exhibited obviously prolonged escape latency(P<0.05),reduced frequency of crossing the platform(P<0.05),and shortened residence time in the target quadrant(P<0.01)when compared with the CON group and the MPH group.HE staining demonstrated that the cells in the PH group were in disordered arrangement,with great loss in cell count in some areas,and widened intercellular spaces.Although the cell arrangement in the MPH group also showed a sparse state,but the condition was milder than that in the PH group,with slightly widened intercellular space.In the CON group and the MCON group,the cells exhibited round in shape,good morphological structure,relatively clear contours,and uniform cell nuclei.TEM revealed that in the hippocampal neurons of the PH group,the mitochondria were swollen and deformed,and mitochondrial cristae were disordered,dissolved and disappeared.In the MPH group,only some mitochondria were swollen and the cristae were reduced.However,the mitochondrial morphology of the CON and MCON groups was relatively complete,and the matrix was uniform.Western blot analysis showed that the expression levels of Parkin and PINK1 in the hippocampus were up-regulated in the PH group than the CON group(P<0.05),and reduced in the MPH group than the PH group(P<0.05).Conclusion Mdivi-1 may reduce hippocampal neuron damage by inhibiting excessive mitophagy and then improve cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol.

Objective To determine the median effective concentration(EC50)of ropivacaine at the volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block in children aged 6 to 10 years.Methods A prospective dose-finding trial was conducted based a sequential Dixon up-and-down allocation.We recruited children aged 6 to 10 years who were scheduled for unilateral surgery on upper extremity regions in our hospital from April to December 2022.All of them were subjected to general intravenous anaesthesia combined with ultrasound-guided interscalene brachial plexus block.The ropivacaine volume for each patient was 0.5 mL/kg.The concentration of 0.2%for the first patient,subsequent concentrations were adjusted based on the block effect of previous patient,increase or decrease by 0.02%.The trial was stopped when there were 7 turning points.Isotonic regression and Bootstrap were used to calculate the values of EC50 and 95%effective concentration(EC95),along with their 95%confidence intervals(CI).General data,incidence of adverse events,and score of postoperative pain were recorded.Results A total of 26 children aged 6 to 10 years were included.The EC50 of ultrasound-guided interscalene brachial plexus block was determined to be 0.091%(95%CI:0.077%～0.105%),and the EC95 was estimated to be 0.117%(95%CI:0.110%～0.118%).Successful blockade was achieved in 16 cases(61.5%),while 10 cases(38.5%)failed.No statistical differences existed between successful and failed cases regarding sex,age,body weight,surgical site,surgical laterality,operative time,or anesthesia duration.None of the patients experienced adverse events such as pneumothorax,vascular injury,or Horner's syndrome,and the score of postoperative pain were all<6 by modified Children's Hospital of Eastern Ontario Pain Scale.Conclusion In children aged 6 to 10 years,the EC50 of ropivacaine is 0.091%at a volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block,and this low dose of regional anesthetic can reduce the risks such as systemic toxicity and direct neurotoxicity.

With the rapid development of modern medicine, anesthesiology is moving towards perioperative medicine. Changing pediatric anesthesiologist into perioperative professionals should focus on training preoperative visits in pediatric anesthesia, intraoperative anesthetic skills, postoperative visits, perioperative pain management, and the prevention and treatment of psychological trauma on the premise of understanding children pathological physiology characteristics. It is the mission of every perioperative pediatrician to ensure children safely and comfortably go through the perioperative period, reduce postoperative complications and mortality, and improve the long-term prognosis.

OBJECTIVE: To compare the median effective dose (ED) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery. METHODS: We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 μg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 μg/kg interval. The ED was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min. RESULTS: The ED value of intranasal dexmedetomidine for sedation was 1.84 μg/kg (95% : 1.68-2.00 μg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 μg/kg (95% : 3.21-3.54 μg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects. CONCLUSIONS In children with acyanotic congenital heart disease, the ED of intranasal dexmedetomidine for TTE sedation increases to 3.38 μg/ kg after cardiac surgery from the preoperative value of 1.84 μg/kg.
Administration, Intranasal ; Cardiac Surgical Procedures ; Child ; Dexmedetomidine ; Heart Defects, Congenital ; surgery ; Humans ; Hypnotics and Sedatives

OBJECTIVE: To investigate the effects of propofol combined with hypoxia on cognitive function of immature rats and the possible role of p38 pathway and tau protein in mediating such effects. METHODS: Ninety 7-day-old (P7) SD rats were randomized for daily intraperitoneal injection of propofol (50 mg/kg) or lipid emulsion (5.0 mL/kg) for 7 consecutive days. After each injection, the rats were placed in a warm box (38 ℃) with an oxygen concentration of 18% (hypoxia), 21% (normal air), or 50% (oxygen) until full recovery of the righting reflex. Another 90 P7 rats were similarly grouped and received intraperitoneal injections of p-p38 blocker (15 mg/kg) 30 min before the same treaments. The phosphorylated tau protein, total tau protein and p-p38 content in the hippocampus were detected using Western blotting. The spatial learning and memory abilities of the rats were evaluated with Morris water maze test. RESULTS: Compared with lipid emulsion, propofol injection resulted in significantly increased levels of p-p38, phosphorylated tau and total tau proteins in rats with subsequent hypoxic or normal air treatment ( < 0.05), but propofol with oxygen and injections of the blocker before propofol did not cause significant changes in the proteins. Without subsequent oxygenation, the rats receiving injections of propofol, with and without prior blocker injection, all showed significantly prolonged latency time and reduced platform-crossing times and third quadrant residence time compared with the corresponding lipid emulsion groups ( < 0.05). With oxygen treatment, the rats in propofoland blocker-treated groups showed no significant difference in the performance in Morris water maze test from the corresponding lipid emulsion group. The results of Morris water maze test differed significantly between blocker-propofol group and propofol groups irrespective of exposures to different oxygen levels ( < 0.05), but not between the lipid emulsion and blocker group pairs with exposures to different oxygen levels. CONCLUSIONS Propofol combined with hypoxia can affect the expression of tau protein through p38 pathway to impair the cognitive function of immature rats, in which oxygen plays a protective role.
Animals ; Cognitive Dysfunction ; etiology ; metabolism ; Hippocampus ; chemistry ; Hypnotics and Sedatives ; pharmacology ; Hypoxia, Brain ; complications ; metabolism ; MAP Kinase Signaling System ; Maze Learning ; drug effects ; physiology ; Memory ; drug effects ; physiology ; Propofol ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; analysis

Objective To evaluate the effect of hypoxemia factor on hippocampal long-term potentiation(LTP)in newborn rats undergoing propofol anesthesia. Methods Forty-two pathogen-free healthy Sprague-Dawley rats(21 males,21 females),aged 7 days,weighing 14-18 g,were divided into 3 groups(n=14 each)using a random number table:propofol plus air group(group PA),propofol plus pure oxygen group(group PO)and intralipid plus pure oxygen group(group IO).Propofol 50 mg/kg was injected intraperitoneally once a day for 7 consecutive days in PA and PO groups. Intralipid 5.0 ml/kg was injected intraperitoneally once a day for 7 consecutive days in IO group. The rats were exposed to air or pure oxygen for 6 h after the end of each injection. The arterial oxygen saturation and respiratory rate were determined after administration. The rats were returned to the cage after recovery of righting reflex. Six rats in each group were selected for preparation of hippocampal slices at 24 h after the last injection on 7th day,and the electric stimulation-induced field excitatory post synaptic potential(fEPSP)and success rate of LTP induction were recorded. Morris water maze test was performed in the other rats at 2 weeks after administration to assess the cognitive function. Results Compared with group IO,the respiratory rate,amplitude of fEPSP and success rate of LTP induction were significantly decreased,and the escape latency was prolonged in group PO(P<0.05).Compared with group PO,the arterial oxygen saturation,amplitude of fEPSP and success rate of LTP induction were significantly decreased,the escape latency was prolonged,and the number of crossing the original platform was decreased in group PA(P<0.05).Conclusion Hypoxemia factor increases propofol-induced neurotoxicity in the central nervous system of newborn rats.

Objective To investigate the effects of different modes of one-lung ventilation (OLV) on hemodynamies in the patients undergoing thoracic operation.Methods Forty-five adult patients undergoing thoracic surgery,were randomly allocated into 3 groups based on the modes of OLV used ( n =15 each):intermittent positive pressure ventilation ( IPPV,VT 6-8 ml/kg,RR 10-14 bpm,I:E 1:2) group,IPPV + positive end-expiratory pressure (PEEP) group and IPPV + continuous positive airway pressure (CPAP) group.Double-lumen tube was inserted.Conrrect positioning was verified by fiberoptic bronchoscopy.The patients were mechanically ventilated.PETCO2 was maintained at 35-45 mm Hg.In group IPPV + PEEP,OLV was performed for 30 min with PEEP of 5 cm H2O and then for another 30 min with PEEP of 10 cm H2O.In group IPPV + CPAP,OLV was performed with IPPV in the lung on the ventilated side and with CPAP of 5 cm H2O in the lung on the operated side (for 1 h).MAP,HR,cardiac output (CO),cardiac index ( CI),stroke volume (SV),and stnoke volume index (SVI) were recorded before induction of anesthesia,at 10 min after intubation,at 30 min of two-lung ventilation,at 30 min and 1 h of OLV,and at the end of operation ( T1-6 ).Arterial blood samples were taken at T1,2,4-6 for blood gas analysis.The levels of blood glucose and lactate were measured.Oxygen delivery ( DO2 ) and DO2 index ( DO2I) were calculated.Results Compared with IPPV group,SV,SVI,CO,CI,DO2 and DO2I were significantly decreased at T4,5 ( P ＜ 0.05),and no significant change was found in the levels of blood glucose and lactate in group IPPV + PEEP,and no significant change was found in the parameters mentioned above in group IPPV + CPAP ( P ＞ 0.05).Compared with IPPV + PEEP group,SV,SVI,CO,CI,DO2 and DO2I were significantly increased at T4,5 ( P ＜ 0.05),and no significant change was found in the levels of blood glucose and lactate in group IPPV + CPAP ( P ＞ 0.05).Conclusion It exerts no influence on hemodynamics using OLV with IPPV in the lung on the ventilated side and with CPAP of 5 cm H2O in the lung on the operated side,however,OLV with IPPV + PEEP can result in hemodynamic fluctuation,but the degree of fluctuation is lesser and DO2 can be maintained in the patients undergoing thoracic operation.

Problems which should be emphasized in pediatric anesthesiology teaching were expounded based on anesthesia teaching practice and requirements of the cultivation 21 century anesthesia professionals.This paper emphasized the special anatomical,physiological and pharmacological characteristics of children,preoperative preparation,building of moral and legal concept and self-learning ability.

ObjectiveTo investigate the effect of propofol repeated anesthesia on the expression of CaMK Ⅱ α in the hippocampus in neonatal rats.MethodsThirty-two SD rats aged 7 days weighing 12-16 g were randomly divided into 2 groups (n =16 each): group C received intraperitoneal 0.9％ normal saline 7.5 ml/kg once a day for 7 days and group P received propofol 75 mg/kg once a day for 7 days.Learning and memory function were assessed using Morris warier maze at 28 days old of rats.The animals were sacrificed at 24 h after the tests and brain tissues were removed.The expression of CaMK Ⅱ α and phosphorylated CaMK Ⅱ α (pCaMK Ⅱ α) in hippocampal CAI region were determined by immunochemistry and Western bolt.ResultsCompared with group C,the escape latency was significantly prolonged,space exploration time shortened and expression of CaMK Ⅱ α and pCaMK Ⅱ α down-rugulated in group P than in group C( P ＜ 0.01 ).ConclusionPropofol repeated anesthesia decreases congnitive function through down-regulating the expression and inhibiting the activity of CaMK Ⅱ α in hippocampus in neonatal rats.

Objective To investigate the effect of propofol on the learning and memory function in neonatal rats under hypoxic conditions. Methods Eighty-four 7-day-old SD rats were randomly divided into 6 groups (n = 14 each): propofol + 18% oxygen (propofol-hypoxia, group PH), propofol + air (group PA), propofol +100% oxygen (propofol-oxygen, group PO), 0.9% normal saline (NS) + 18% oxygen (group CH), NS + air (group CA), NS + 100% oxygen (group CO). The rats received injection of intraperitoneal propofol 50 mg/kg or NS 5.0 ml/kg once a day for 7 consecutive days and they were exposed to 18% oxygen, air or 100% oxygen at the end of each injection. SaO2 and respiratory rate (RR) were monitored and recorded after administration. The rats were returned to the cage after recovery of the righting reflex. Six rats in each group were sacrificed 24 h after the 7th injection, and the brain tissues were taken to observe the apoptosis in hippocampal neurons. Morris water maze test was used to test the learning and memory function 2 weeks after administration in the other rats. Results RR was significantly lower and the escape latency at T1.2 longer in group PO than in group CO (P ＜ 0.05). RR and SaO2 were significantly decreased, apoptotic index was increased, the escape latency was prolonged and the frequency of crossing the original platform was reduced in group PA compared with group CA, and in group PH compared with group CH (P ＜ 0.05). Compared with group PO, SaO2 was significantly decreased, apoptotic index was increased, the escape latency was prolonged and the frequency of crosing the original platform was reduced in group PA (P ＜ 0.05). Conclusion Propofol induces apoptosis in hippocampal neurons and decreases the learning and memory function in neonatal rats under hypoxic conditions.