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 investigate the clinical characteristics of R403C variant in DNM1L gene caused encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (EMPF1).Methods:The clinical data of three patients, who carried R403C variant in the DNM1L gene, diagnosed at Xiangya Hospital from February 2018 to February 2020 were retrospectively summarized. Literature reviewing was performed by taking "DNM1L" or "encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1" as keywords for searching in online Mendelian inheritance in man (OMIM), PubMed, China national knowledge infrastructure (CNKI), and Wanfang data knowledge service platform up to July 2020. And the clinical manifestation, laboratory examination, imaging, treatment, and prognosis were reviewed.Results:Case 1, a 7-year-old boy, developed seizures after a 9-day course of cough without fever. The seizures manifested as generalized tonic-clonic seizures (GTCS) and soon converted to focal status epilepticus (EPC) or focal myoclonus, which were resistant to multi-anti-epileptic drugs combined with sedative drugs. The boy died at the 2 nd week after seizure onset. Case 2, also a 7-year-old boy, developed seizures after a 10-day history of amygdalitis. The seizures manifested as focal to generalized tonic-clonic seizure and then converted to EPC or focal myoclonus. And all seizures showed poor responses to multi-anti-epileptic drugs combined with sedative drugs, ketogenic diet, and methylprednisolone treatment. The boy died after 1 month′s treatment. Case 3, a 3-year and 5-month old girl, had seizures onset after a 2-week course of viral pneumonia. The seizures onset manifested as focal clonic seizure and converted to EPC, shortly. She was resistant to multi-anti-epiletic drugs combined with sedative drugs and ketogenic treatment. The girl died 3 months afte seizure onset. All of their images showed multifocal T1 low, T2, fluid attenuated inversion recovery, and diffusion-weighted imaging high signal lesions among the brain, and diffuse brain atrophy in case 3. The blood metabolic and cerebrospinal-fluid immunological assays were normal. Genetic analysis suggested a de novo, heterozygous, NM_012062.4: c.1207C>T, p.R403C variant in the DNM1L gene. According to their clinical manifestations, all of them were diagnosed with EMPF1. Literature review included 11 patients carrying this variant in the world. Summarizing the 14 cases, 8 cases had an infectious history before seizure onset, 8 cases had mild or moderate development delay. All of 14 cases had seizures, and the forms mainly included EPC ( n=9), focal myoclonus ( n=6), GTCS ( n=5) and focal clonic seizures ( n=4). All of them were refractory, and no effective anti-epileptic drugs were recommended. Early-stage cranial magnetic resonance imaging results showed multiple intracranial focal lesions ( n=10), including thalamus ( n=7), hippocampus ( n=5), basal ganglia ( n=4), frontal lobe ( n=3), and temporal lobe ( n=2). As the disease progressed, the brain manifested as diffused progressive atrophy ( n=10). Five of the 14 cases died at reported age. Conclusions:R403C variant in the DNM1L gene can cause mitochondrial fission dysfunction. Patients carrying this variant may manifest as refractory status epilepticus with or without mild-infection indction, development regression and brain atrophy.

Objective:To evaluate the application of 3D printed osteotomy template in total knee arthroplasty (TKA) for valgus knee.Methods:A retrospective analysis was performed of the 21 patients with valgus knee who had undergone TKA at Department Ⅰ of Joint Surgery, Orthopaedics Hospital of Zhengzhou from March 2016 to February 2018. They were 5 males and 16 females, aged from 62 to 78 years (average, 66.7 years). TKA was performed with the assistance of a 3D printed personalized osteotomy template for each patient. The efficacy of the personalized osteotomy templates was evaluated by comparing the femorotibial angle, knee range of motion, Hospital for Special Surgery (HSS) knee scores of the patients between preoperation and postoperation.Results:The 21 patients were followed up for a mean duration of 16.3 months(range, from 10 months to 4 years). All incisions healed by the first intention. The last follow-ups showed that their preoperative femorotibial angle 17.6°±5.7° was improved significantly to 6.3°±1.2°, their preoperative knee range of motion 71.3°±5.8° increased significantly to 102.4°±7.5°, and their preoperative HSS scores 38.2±5.7 increased significantly to 87.5±3.5 ( P<0.001). Their radiographic evaluation at the last follow-up showed stable prosthetic components with no implant loosing or osteolysis. Conclusion:A personalized 3D printed osteotomy template can be used in TKA for valgus knee, leading to accurate osteotomy, effective correction of mechanical alignment and satisfactory clinical outcomes.