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 investigate the characteristics and causes of cardiac ADR induced by quinolones,and to provide reference for clinical treatment. METHODS:Three thousaud two hundred and eighty-eighe 8 patients receiving common quinolones were selected from clinical departments in Zhengzhou Central Hospital of Zhengzhou University during Mar. 2012-Mar. 2016. Retro-spective analysis was conducted in terms of patients’age and gender,clinical departments,main clinical manifestations,route of administration,underlying disease,drug combination. The reasons for cardiac ADR were analyzed. RESULTS:Among 3 288 pa-tients,there were 34 patients(1.03%)with cardiac ADR. Among them,the incidence of cardiac ADR in patients over 50 years old was as high as 76.47%;patients with cardiac ADR were mainly in the respiration department,gastroenterology department and urology department,accounting for 76.47%;most of patients were from gastroenterology department(29.41%). In cardiac ADR, the main clinical manifestations were QTc interval prolongation torsadesde poiutes(TdP)and TdP,accounting for 58.82%. Among them,patients with QTc interval prolongation TdP occupied the highest proportion,there was no statistical significance compared to TdP(P>0.05);there was statistical significance in the difference with other clinical manifestations(P<0.05). Among common-ly used quinolones,levofloxacin(32.35%)and ciprofloxacin(41.18%)caused large proportion of cardiac ADR,there was statisti-cal significance compared to norfloxacin,moxifloxacin and other quinolones(P<0.05). The proportion of cardiac ADR induced by intravenous dripping(91.18%)was much higher than oral administration(8.82%),with statistical significance(P<0.05). Among patients with cardiac ADR,the patients with underlying disease (94.12%) and drug combination (91.18%) occupied the higher proportion,there was statistical significance compared to the patients without underlying disease and drug combination(P<0.01). Among drug combination,the patients receiving amiodarone (29.41%) and salbutamol (20.59%) occupied the large proportion, there was statistical significance compared to other types of drug combination(P<0.05). CONCLUSIONS:Cardiac ADR induced by quinolones in our hospital mostly occurs in respiration department,gastroenterology department and urology department,and mainly manifests as QTc interval prolongation TdP and TdP. The incidence of cardiac ADR may be greatly increased in elderly pa-tients,patients with underlying diseases,and drug combination as well as intravenous infusion. Therefore,clinicians should select suitable quinolones,and make reasonable individualized dosage regimen.

Objective:To evaluate the outcomes of lesser arc perilunate injuries (Perilunate disloca-tions)treated with arthroscopically assisted mini-invasive reduction and fixation.Methods:Between 2012 and 2014,5 patients who had a perilunate dislocation were treated with arthroscopically assisted re-duction and percutaneous fixation.The mean follow-up was 17.8 months (range,10 to 32 months). Clinical outcomes were evaluated on the basis of range of motion;grip strength;Mayo wrist score;Quick disabilities of the arm,shoulder and hand questionnaire;and patient-rated wrist evaluation score.Radio-graphic evaluations included carpal alignments and any development of arthritis.Results:The range of flexion-extension motion of injured wrist averaged 84% of the values for contralateral wrist.The grip strength of the injured wrist averaged 90% of the values for the contralateral wrists.The mean Quick Disabilities of the arm,shoulder and hand score was 1 ,and the mean Patient-Rated Wrist Evaluation score was 5 .According to the Mayo wrist scores,the overall functional outcomes were rated as excellent in all the patients.Reduction obtained during the operation was maintained within normal ranges in all the patients.Arthritis had not developed in any patient at the end of the follow-up.Conclusion:Arthroscopic mini-invasive reduction with percutaneous fixation is a reliable and favorable alternative in the treatment of perilunate dislocations according to our early results.