Objective To observe the effect of hippocampal DNA methyltransferases (DNMTs)on neonatal cognitive impairments induced by sevoflurance exposure.Methods Sixty-four 7-day old male Sprague-Dawley rats were randomly divided into the following four groups (n =1 6):control group (group C),sevoflurane group (group S),sevoflurane+NaCl group (group SN),and sevoflurane+5-AZA group (group SA).Sevoflurane animals received 3% sevoflurane plus 30% oxy-gen for 2 hours daily for 3 consecutive days,and rats in group C were placed into the same container, which contained 30% oxygen only.Animals in group SA were intracerebroventricularly injected with 5-AZA (1 mg/kg),while group SN same volume of NaCl one hour before sevoflurane exposure. Open field and Morris water maze were given the four weeks after anesthesia (n =8).Rats without any behavior tests from each group (n =8)were euthanized 4 weeks after the treatment and the hip-pocampus was harvested.Quantitative real-time PCR and Western blot were used to detect the mRNA and protein levels of DNMT1,DNMT3a and DNMT3b.Results In the open field test,no significant difference was observed in the distance travelled and the time spent in the center of the arena.Com-pared with the group C,group S showed an increase in the latency,decreased time spent in the target quadrant,and the mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus were sig-nificantly increased (P < 0.05).Compared with the group SN,group SA showed a decrease in the la-tency,more time spent in the target quadrant,and the mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus were decreased (P < 0.05).There was no significant difference in the expression of DNMT1 among the four groups.Conclusion Sevoflurane exposure induces neonatal cog-nitive impairments later in life,which was accompanied by the increased mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus.By contrast,pretreatment of 5-AZA decreased hipp-ocampal DNMT3a and DNMT3b,and ameliorated cognitive impairments.These results suggest that DNMTs are involved in sevoflurane induced neonatal cognitive impairments.

Objective To investigate the expression of parvalbumin (PV)in the cognitive im-pairment mice induced by sevoflurane anesthesia,and to explore whether enriched environment could reverse it.Methods One hundred and forty-four Six-day-old C57BL/6 male mice at postnatal day 6 were randomly divided into the following four groups (n =36):control+standard environment group (group CS),control+enriched environment group(group CE),sevoflurane anesthesia+standard en-vironment group(group SS)and sevoflurane anesthesia+enriched environment group(group SE).An-imals were exposed to 3% sevoflurane plus 30% O 2 or 30% O 2 2 h daily for 3 days from postnatal day 6 (P6)to P8.The exposed pups were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or to a standard environment.Western blotting were used for determining PV ex-pression in the prefrontal cortex and hippocampus at P9,P14,P42,P60 and P90.Cognitive functions were assessed by performing the open field (P41 ),and fear conditioning tests (P42-43 and P89-90, respectively).Results In the open field test,there was no significant difference in the total travel dis-tance and the time spent in the center of the arena among groups.In the contextual fear condition test, compared with group CS,the group SS only exhibited a reduced freezing response in the contextual test at P43,but not at P90.In the cued fear conditioning test,no difference was observed in the freez-ing time among the four groups.The PV expression in the prefrontal cortex and hippocampus of group SS were significantly lower than that of group CS at P9 and P14 (P <0.001),while recovered at P60 and P90.The PV expression in the prefrontal cortex and hippocampus of group SE were significantly higher than that of group SS at P42 (P <0.05).Linear regression analysis demonstrated a positive correlation between the PV expression in the prefrontal cortex and the freezing time induced by envi-ronment (r =0.670 7,P =0.000 1),and there was a positive correlation between the PV expression in hippocampus and the freezing time induced by environment (r = 0.509 6,P = 0.001 9 ). Conclusion The cognitive impairment induced by sevoflurane anesthesia may be associated with the reduction of PV in the prefrontal cortex and hippocampus.Placement of the sevoflurane-exposed mice in an enriched environment prevented the development of these abnormalities.

Objective To analyze the effect of different anesthesia induction time on postoperative circadian rhythm in patients undergoing robot-assisted radical prostatectomy.Methods A total of 103 pa-tients,aged 50-85 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ,undergoing robot-assisted radi-cal prostatectomy from January 2022 to October 2022 were recruited.The patients were grouped according to the induction time:the morning 8:00-11:59 group(group M,n=53)and the afternoon 12:00-18:00 group(group A,n=50).D'Amico risk grade,duration of anesthesia,number of effective com-pressions of analgesic pump(D1)and actual compressions(D2)were recorded,D1/D2 were calculated.HR,MAP,SpO2 were recorded at 5 minutes after entrying the operation room(T0),5 minutes after anes-thesia induction(T,),5 minutes after the surgery start(T2),60 minutes after the surgery start(T3),at the end of surgery(T4)and 5 minutes after extubation(T5).BIS at T1-T4 were recorded.Sleeping status was assessed by the Athens insomnia scale(AIS)1 day before surgery,1 day and 3 days after surgery,and pain level was assessed 1 and 3 days after surgery using the digital rating scale(NRS).According to the re-sults of the morningness-eveningness questionnaire of sleep-wake assessment(MEQ-SA)1 day before surgery and 3 days after surgery,the patients'circadian rhythm was determined.Results There were no statistically significant differences in D'Amico risk grade,duration of anesthesia,D1/D2,HR,MAP,SpO2 and BIS at different time point,AIS scores 1 day before surgery,1 day and 3 days after surgery,and NRS scores 1 day and 3 days after surgery between the two groups.In group M,there were 11 cases(21％)of circadian rhythm changes,of which 5 people's circadian rhythm changed to"later"and 6 people's circadian rhythm changed to"earlier".In group A,there were 3 cases(6％)of circadian rhythm changes,of which 1 person's circadian rhythm changed to"later"and 2 people's circadian rhythm changed to"earlier".The rate of circadian rhythm change in group M was significantly higher than that in group A(P＜0.05).Conclusion The incidence of perioperative circadian rhythm alteration is significantly higher in patients undergoing robot-assisted radical prostatectomy who starts anesthesia in the morning than those in the after-noon.

Vagus nerve is the main undertaker of the parasympathetic nervous system,participating in the regulation of inflammatory response and playing the role of organ function protection.Stimulation such as perioperative operation and anesthesia can often lead to a relative decrease in vagus nerve tension and in-crease in perioperative circulation,respiration,digestion,nerve,and other system-related complications.This article mainly reviews the effects of reduced vagal tone on perioperative multiple organ functions and va-gus nerve stimulation in organ function,aiming to provide new ideas for reducing various perioperative com-plications.

Objective:To evaluate the relationship between the severity of preoperative brain injury and postoperative delirium (POD) in elderly patients using latent class analysis based on markers of brain injury.Methods:One hundred and thirty-one American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 65-84 yr, with a body mass index of 18-28 kg/m 2, scheduled for elective unilateral total hip arthroplasty in our hospital, were selected. Cognitive function was assessed using the Mini-Mental State Examination before surgery. Arterial blood samples were collected before anesthesia to measure the plasma concentrations of brain-derived neurotrophic factor, inducible nitric oxide synthase, prostaglandin E2, central nervous system-specific protein (S100β), glial fibrillary acidic protein, neurofilament light chain, matrix metalloproteinase-9, fibroblast growth factor 23, complement 3, complement 3a, complement 5a and irisin using enzyme-linked immunosorbent assay. POD was evaluated using the Confusion Assessment Method within 3 days after operation, and the patients were divided into POD group and non-POD group. The patients were divided into different injury severity subtypes based on the levels of brain injury markers using latent class analysis, and logistic multivariate regression was used to analyze the independent risk factors for POD. Results:Compared with non-POD group, the concentrations of neurofilament light chain, glial fibrillary acidic protein, S100β and prostaglandin E2 were significantly different in POD group ( P<0.05). Using these four brain injury markers for latent class analysis, patients were divided into a high severity of brain injury group (91.51%) and a low severity of brain injury group (8.49%). The results of logistic multivariate regression analysis showed that subtypes of brain injury ( OR=8.31, 95% confidence interval [ CI] 1.77-38.90, P=0.007), age ( OR=1.14, 95% CI 1.03-1.24, P=0.007), and plasma irisin concentrations ( OR=0.99, 95% CI 0.98-0.99, P=0.027) were independent risk factors for POD. Conclusions:Higher severity of preoperative brain injury is an independent risk factor for POD in elderly patients.

Objective To explore changes in the functional network in an animal model of SAE induced by lipopolysaccharide (LPS) challenge.Methods Thirty male Sprague-Dawley rats were randomly allocated into control group and group SAE.SAE model was established by intraperitoneal injection of LPS 1 mg/kg in group SAE, while the same amount of saline.was injected in the control group.Firstly, we used regional homogeneity (ReHo) method to exam abnormal brain regions between the control and SAE groups and then considered them as seeds for functional connectivity analysis, and behavioral tests were performed at 48 hours after LPS intraperitoneal injection.Results Compared with the control group, our study showed LPS impaired mood function, as reflected by depression-like behavior of prolonged immobility[ (38.93± 13.84) s vs (22.06± 6.75) s, P<0.05]in the forced swim test;LPS induced significantly increased ReHo values in the anterior cingulate cortex (ACC) and caudate putamen (CPu) of (1.21±0.07 vs 0.97±0.12, P<0.05) and (1.34±0.09 vs 1.17±0.16, P<0.05) respectively;the ACC seed showed increased functional connectivity with the retrosplenial cortex (0.45 ± 0.06 vs 0.11 ± 0.02, P<0.05) ;the right CPu seed showed increased functional connectivity with the left Cpu (0.33±0.07 vs 0.07±0.01, P<0.05) ;the depression-like behavior was associated with increased ReHo values in the ACC and right CPu as well as increased functional connectivity between the right CPu and left CPu.Conclusion This study suggests that the impaired mood function in SAE is associated with increased ReHo values in the ACC and right CPu as well as increased functional connectivity between the right CPu and left CPu, indicating that the abnormality of resting-state functional network may be a potential mechanism involved in SAE.

Objective To observe whether ketamine improves the symptoms of post-traumatic stress disorder (PTSD).Methods Sixty male SD rats were randomized into four groups:groups CN,CK,PN and PK,15 in each.PTSD animal model was established by inescapable foot shock (IFS) procedure.In groups PK and CK,rats were treated with ketamine 2.5 mg/kg by intraperitoneal injection beginning at 30 min after the IFS procedure once a day for 14 days.Twelve rats were used for be havioral tests,and the others were sacrificed to collect hippocampus tissues for Western blot in each group 14 d after IFS procedure,respectively.The expression of neuroligin (NLGN)-1 was detected by Western blot.Results In the fear conditioning test,compared with group CN,the percent age of freezing time in total time in group PN was significantly increased (P＜0.01).Compared with group PN,the percent age of freezing time in PK group was significantly decreased (P＜0.01).In the water maze test,compared with group CN,the escape latency of group PN was significantly increased on day 2,3,4,5 of training period (P＜0.05).Compared with group PN,the escape latency of group PK was significantly decreased on day 2,4,5 of training period (P＜0.05).There was no significant difference in the time spent in the target quadrant.The expression of NLGN-1 in the hippocampus was significantly increased in PN group compared with group CN (P＜0.05);compared with group PN,the expression of NLGN-1 in the hippocampus was significantly decreased in PK group (P＜0.05).Conclusion The study suggest that the fear memory is significantly,increased and the hippo campus-dependent spatial learning capacity is impaired in the PTSD model rats.And the increased ex pression of hippocampal NLGN-1 may be involved in the development of PTSD.Ketamine mediated down regulation of NLGN-1 in the hippocampus might contribute to attenuating the fear memory and improving the hippocampus dependent spatial learning in the PTSD model rats.

Sevoflurane is a commonly used inhalation anesthetic in childrenjs general anesthesia, which may have some adverse effects on brain development. This review discusses the effects of sevoflurane anesthesia on developing brain, based on the characteristics of developing brain tissue, the effects on developing brain function, the mechanism of sevoflurane neurotoxicity and the strategies to reduce sevoflurane anesthesia neurotoxicity, so as to provide reference for clinical application.

Objective　To investigate the role of the p75 neurotrophic receptor (p75 NTR) in the cognitive impairment induced by laparotomy surgery of aged mice,and to explore the possible mechanism.Methods　Thirty eighteen-month-old male mice were equally randomized into three groups (n=10):control group,surgery group,surgery+TAT group.Open field test was performed 5 days after the surgery to record the exploration distance and the time in the center.Fear-conditioned training was performed 6 days after the surgery,and fear-conditioned test was performed 7 days after the surgery to record the freezing time.The hippocampus was harvested immediately after the behavioral test.Western blot was applied to detect the levels of p75NTR,BDNF,PSD95,TrkB and pCREB in the hippocampus,immunofluorescence was applied to detect the number of caspase-3 positive cells in the hippocampus,and Golgi staining was applied to observe the changes of dendritic spines in hippocampal CA-1 region.Results　In the open field test,the total distance and the time in the center had no significant difference among the three groups (P>0.05).In the fear conditioning test,compared with control group,the percentage of the contextual conditional freezing time decreased significantly in surgery group (P<0.05),and the expressions of BDNF，PSD95，TrkB and pCREB and the number of dendritic spines in CA-1 were significantly decreased (P<0.05),the expression of p75NTR and the number of caspase-3 positive cells were increased significantly in the surgery group (P<0.05).Compared with the surgery group,the percentage of the contextual conditional freezing time increased significantly in surgery+TAT group,and the expressions of BDNF,PSD95,TrkB,and pCREB and the number of dendritic spines in CA-1 were significantly increased,the number of caspase-3 positive cells were decreased significantly in the surgery+TAT group (P<0.05).Conclusion　Hippocampal p75 NTR plays a key role in the pathophysiology of POCD.