Objective To explore the sex differences in drug metabolism of sufentanil in Chinese patients based on the mutation classification of cytochrome P450 3A(CYP3A)enzymes.Methods According to the possible effects of combined cytochrome P450 3A4 gene*1G locus(CYP3A4*1G)and cytochrome P450 3A5 gene*3 locus(CYP3A5*3)mutation groups on Chinese population,we added different weights to CYP3A4*1G and CYP3A5*3 polymorphisms and classified patients into 3 groups:GroupⅠ,patients carried either the CYP3A4*1G/*1G allele or both CYP3A4*1/*1G allele and CYP3A5*3/*3 allele;Group Ⅱ,patients with both CYP3A4*1/*1G allele and CYP3A5*1/*3 allele;Group Ⅲ,patients with either the CYP3A4*1/*1 allele or both CYP3A4*1/*1G allele and CYP3A5*1/*1 allele.A single-dose,double-blind,stratified random sampling was performed,and 255 patients undergoing endoscopic surgery in the First Affiliated Hospital of Army Medical University were finally subjected.According to the results of genetic testing,an independent statistician,before operation,randomly selected 30 patients from each stratified group to form a study cohort(male-female ratio of 1∶1)and named each group A,B or C.Clinical investigators and subjects kept double-blind to the results of grouping and genetic testing.After entering the operating room,the subjected 90 patients received a single dose of sufentanil followed by collection of blood samples at 10 time points including 2 min before and from 2 to 120 min after administration.After the surgery,we determined the plasma drug concentration,calculated the pharmacokinetic parameters,and compared the metabolic differences between different genders in each group and unblinded the study.Results The cohort best fitted the two-compartment pharmacokinetic model,and groups A,B and C corresponded to group Ⅰ,Ⅱand Ⅲ,respectively.In different patient groups based on mutatron types of CYP3A enzymes the females had lower plasma drug concentration-time curves at each time point,higher systemic clearance(P≤0.01)and smaller area under the plasma concentration-time curve from zero to infinity(P＜0.05)when compared with the males.In addition,in group Ⅰ,the elimination rate of central compartment and movement rate of drug from central compartment to peripheral compartment were obviously greater in the females than the males(P＜0.05),while the distribution half-life(P＜0.05)and elimination half-life(P＜0.01)were notably longer in the males than the females.In both group Ⅱ and group Ⅲ,the males obtained larger total area under the plasma concentration-time curve than the females(P＜0.05).Conclusion There are sex differences in the drug metabolism of sufentanil in Chinese patients.Women show faster distribution and higher clearance of sufentanil while men present greater drug exposure.Preoperative CYP3A genotyping and intraoperative personalized medication are of great significance to ensure the safety in clinical practice.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Objective To analyze the factors related to early allograft dysfunction(EAD)after liver transplantation and to construct a predictive model.Methods A total of 375 patients who underwent liver transplantation in our hospital from December 2008 to December 2021 were collected,including 90 patients with EAD and 266 patients without EAD.Thirty items of baseline data for the 2 groups were compared and analyzed.Aftergrouping in a ratio of 7∶3,univariate and multivariate logistic regression analyses were used in the training set to evaluate the factors related to EAD and construct a nomogram.Receiver operating characteristic(ROC)curve,decision curve analysis(DCA),sensitivity,specificity,positive predictive value,negative predictive value,Kappa value and other indicators were used to evaluate the model performance.Results The incidence of EAD after liver transplantation was 24%.Multivariate logistic regression analysis showed that preoperative tumor recurrence history(OR=3.15,95%CI:1.28～7.77,P=0.013)and operation time(OR=1.22,95%CI:1.04～1.42,P=0.015)were related to the occurrence of EAD after surgery.After predicting the outcome according to the cut-off point of 0.519 identified by the Youden index,the model performance in the both training set and validation set was acceptable.DCA suggested the model has good clinical applicability.Conclusion The risk factors for EAD after liver transplantation are preoperative tumor recurrence history and operation time,and the established model has predictive effect on prognosis.

Objective:To evaluate the relationship between degrees of biliary obstruction and levels of lipid peroxidation in patients.Methods:A total of 140 patients of both sexes, with biliary obstruction, without biliary puncture and drainage, aged 40-64 yr, with body mass index of 18.5-23.9 kg/m 2, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, were selected.The patients with different degrees of biliary obstruction were divided into 4 groups ( n=35 each) according to Child-Pugh grade total bilirubin (TBIL) concentrations: group A (TBIL<17 μmol/L), group B (17 μmol/L≤TBIL<34 μmol/L), group C (34 μmol/L≤TBIL<51 μmol/L) and group D (TBIL≥51 μmol/L). The serum TBIL, direct bilirubin (DBIL), indirect bilirubin (IBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and malondialdehyde (MDA) concentrations were measured.The correlation between serum MDA concentration and degree of biliary obstruction was tested by Spearman correlation analysis. Results:Compared with group A and group B, the serum DBIL, IBIL, ALT, AST, TBA and MDA concentrations were significantly increased in group C and group D ( P<0.05), and there was no significant difference in the parameters mentioned above between group A and group B ( P>0.05). Compared with group C, the serum DBIL, IBIL, ALT, AST, TBA and MDA concentrations were significantly increased in group D ( P<0.05). Serum MDA concentration was positively correlated with degree of biliary obstruction ( r=0.54, P<0.05). Conclusion:The degree of biliary obstruction can reflect the level of lipid peroxidation in patients.

Clinical teaching round is one of main teaching methods during standardized training for residents. However, the particularity of standardized resident training in clinical anesthesia determines that it is difficult to apply the teaching round model of other disciplines. In this study, seven core contents of Mini-Clinical Evaluation Exercise (Mini-CEX) were modified after considering the characteristics of anesthesia specialty and applied to the teaching rounds of standardized training for residents of anesthesia , thus promoting the standardization and improving the quality of anesthesia teaching rounds.

Objective To evaluate the effects of melatonin on the excitability of pyramidal neurons in the prefrontal cortex and the role of melatonin receptor 1 (MT1 R)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway.Methods Brains were obtained from male SpragueDawley rats between 14 and 21 days after birth.The brain slices of 350-μm thick were prepared and placed in artificial cerebrospinal fluid.The brain slices were divided into 5 groups (n =6 each) using a random number table method:control group (C group),melatonin group (M group),MT1/2R antagonist luzindole plus melatonin group (L+M group),MT2R antagonist 4P-PDOT plus melatonin group (P+M group) and PKA inhibitor Rp-cAMPS plus melatonin group (R+M group).Cells were perfused for 2 min with artificial cerebrospinal fluid in group C.Cells were perfused for 2 min with 1 μmol/L melatonin in group M.Cells were perfused for 2 min with the mixture of 1 μmol/L MT1/2R antagonist luzindole and 1 μmol/L melatonin in group L+M.Cells were perfused for 2 min with the mixture of 1 μmol/L MT2R antagonist 4P-PDOT and 1 μmol/L melatonin in group P+M.In group R+M,1 mmol/L PKA inhibitor Rp-cAMPS was continuously added to the pipette solution,and cells were perfused for 2 min with 1 μmol/L melatonin.The whole-cell patch-clamp technique was used to record the membrane potential and clamp current of pyramidal neurons in the prefrontal cortex.Results Compared with group C,the clamp current was significantly increased,and the membrane potential was decreased in group M (P＜0.05).Compared with group M,the clamp current was significantly decreased,and the membrane potential was increased in L + M and R + M groups (P＜0.05),and no significant change was found in the clamp current or membrane potential in group P+M (P＞0.05).Conclusion Melatonin inhibits the excitability of pyramidal neutrons in the prefrontal cortex,and the mechanism is related to activating MT1 R-cAMP-PKA signaling pathway.

Objective To evaluate the relationship between prefrontal cortex and propofol-induced cognitive dysfunction in rats. Methods SPF healthy male Sprague-Dawley rats, weighing 300-350 g, aged 16 weeks, were used in this study. Thirty rats in which catheters were successfully implanted into the prefrontal lobe were divided into 2 groups ( n=15 each ) using a random number table method: control group (group C) and propofol group (group P). In group P, 50μmol/L propofol 0. 5μl was microinjected into the prefrontal cortex at day 7 after operation, and the equal volume of normal saline was given instead in group C. T-maze test and open field test were performed at 15 min after administration. Results Com-pared with group C, the correct rate of selection in T-maze was significantly decreased ( P＜0. 05) , and no significant change was found in the total locomotor or number of rearing in open field test in group P ( P＞0. 05) . Conclusion Prefrontal cortex may be involved in propofol-induced cognitive dysfunction in rats.

Objective To observe the effect of dexmedetomidine on plasma SDF-1 level in in hepatic portal occlusion operation.Methods Fifty patients with live cancer undergoing elective partial hepatectomy were selected,no gender limitation,aged 42 to 71,body mass index(BMI) 18.5 ～ 26.0 kg/m2,ASA grade Ⅱ or Ⅲ.The patients were randomly divided into 2 groups(n=25):control group and dexmedetomidine group.The dexmedetomidine group was performed the pump injection of dexmedetomidine 1 μg/kg at 15 min before induction of anesthesia.After induction the rate was changed to 0.4μg · kg-1 · h-1 until 15 min before the end of operation;the control group adopted the same method for conducting continuous intraverous infusion of the same capaci ty of 0.9％ sodium chloride.The peripheral venous blood was collected in 2 groups at preoperative 1 h (T0),postoperative 1 h (T1),postoperative 1 d (T2),postoperative 3 d(T3).The plasma SDF-1 level was detected by using enzyme-linked immunosorbent assay(ELISA).Results There was no statistically significant difference in liver resection range,blood loss,first porta hepatis vessel occlusion time,anesthesia time and plasma SDF-1 level before surgery between the two groups (P＞0.05).Compared with pre-operation,plasma SDF-11evel at T1,T2,T3 time point was significantly increased (P＜0.05).The plasma SDF-1 level at T1,T2,T3 time point in the dexmedetomidine group was lower than that in the control group(P＜0.05).Conclusion SDF-1 expression is significantly increased during perioperative period in the patients with hepatic portal occlusion operation,and intraoperative continuous dexmedetomidine can significantly reduce the SDF-1 level,which inhibits the chemotaxis and accumulation of inflammatory ceils to some extent.

Objective To dynamically observe the SDF-1 level in plasma,bone marrow,liver,lung and kidney,and to investigate their significance in obstructive jaundice and its complications. Method 48 male SD rats weighing about 200g were randomly divided into Sham group and CBDL group. The serum ALT ,AST and se-rum total bilirubin(TBIL)were detected at 7 d,14 d and 21 d after operation. General condition of rats in the two groups were observed. ELISA was applied in detecting expression of SDF-1 in plasma and supernate of tissue ho-mogenate. And mRNA expression of SDF-1 at different time was detected by qPCR assay. Results ALT,AST,TB increased rapidly after CBDL operation,the difference was significant compared with Sham group(P <0.05). The SDF-1 expression of plasma,liver tissue,lung tissue in CBDL rats at different time points were significantly higher than in Sham group. No significant difference was found in renal tissue. SDF-1 expression of bone marrow in 7 d,14 d,21 d was significantly lower in CBDL group than in Sham group. Conclusion Expression of SDF-1 in liver and lung tissues of obstructive jaundice rats significantly increased ,and decreased in marrow bone. This change may promote related stem cells mobilization and contribute to the pathological changes of obstructive jaun-dice.

Objective To evaluate the effect of dexmedetomidine on pulmonary microvascular en-dothelial cell(PMVEC)injury induced by the serum of mice with renal ischemia-reperfusion(I∕R)injury. Methods Renal I∕R was induced by clamping bilateral renal pedicles for 60 min followed by 24 h of reper-fusion. Primary PMVECs of mice were divided into 3 groups(n=20 each)using a random number table:control group(group C), serum of mice underwent I∕R group(group I∕R)and dexmedetomidine group (group Dex). PMVECs were cultured with 10% serum of mice underwent sham operation in group C. PM-VECs were cultured with 10% serum of mice underwent I∕R injury in group I∕R. PMVECs were incubated for 3 h with dexmedetomidine at the final concentration of 0.1 μmol∕L before incubation with serum in group Dex. At 24 h of culture or incubation, the cell survival rate was detected by CCK8 assay, cell apoptosis by Hoechst 33258 staining, caspase-3 activity using colorimetric method, and the expression of Bcl-2 and Bax using Western blot. Results Compared with group C, the cell survival rate was significantly decreased, the apoptosis rate and activity of caspase-3 were increased, the expression of Bcl-2 was down-regulated, and the expression of Bax was up-regulated in I∕R and Dex groups(P<0.01). Compared with group I∕R, the cell survival rate was significantly increased, the apoptosis rate and activity of caspase-3 were de-creased, the expression of Bcl-2 was up-regulated, and the expression of Bax was down-regulated in group Dex(P<0.01). Conclusion Dexmedetomidine can reduce PMVEC injury induced by the serum of mice with renal I∕R injury, and the mechanism is related to regulating the expression of Bcl-2 and Bax and inhib-iting mitochondrial apoptosis pathway.