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 establish a cutoff level of anti-Müllerian hormone(AMH)which could help with the di-agnosis of polycystic ovary syndrome(PCOS)in adults,and to analyze the risk factors of metabolic syndrome(MS).Methods:A retrospectively analyzed 426 PCOS patients(PCOS group)and 205 healthy controls aged 20-39 years from the Health Checkup Center of the Gynecological Endocrine Center,Hunan Maternal and Child Health Hospital from January 2021 to December 2023.AMH diagnostic validity was estimated by receiver operating characteristic(ROC)curves.Patients were subgrouped into PCOS combined metabolic syndrome group(MS-PCOS)and the uncomplicated MS group(UMS-PCOS)according to metabolic status.Multivariate Logistic regression analysis was performed to determine the risk factors for MS in PCOS patients.Results:The serum AMH level was higher in PCOS group than that in the control group(8.42±3.71 ng/ml vs.2.99±0.94 ng/ml,P＜0.001).AMH cutoff for the diagnosis of PCOS was determined as≥4.87 ng/ml on ROC analysis,and the area under the curve is 0.981 with 92.7％sensitivity and 94.6％specificity.The prevalence of MS was 18.3％(78 ca-ses)in PCOS group.Subgroup analysis showed that MS-PCOS patients had higher waist circumference,BMI,fasting glucose,dyslipidemia,hypertension(BP＞130/85 mmHg),and hormone related index androgen level,but lower AMH vs.UMS-PCOS.Multivariate Logistic regression analysis identified insulin resistance(OR 39.17,95％CI 9.33-164.48),BMI ≥24 kg/m2(OR 3.72,95％CI 1.86-7.45),and hyperandrogenism(OR 2.56,95％CI 1.34-4.89)as independent risk factors of MS.AMH was negatively associated with MS,a single-unit increase in AMH was associated with an 17％decrease in odds of MS(OR 0.83,95％CI 0.73-0.95,P=0.006).Conclusions:Serum AMH levels were significantly higher in adult PCOS patients,with an optimal diagnostic threshold of 4.87 ng/ml.Hyperandrogenism and low AMH levels may predict a higher risk of MS,in addition to metabolism-related factors.

Objective:To establish a cutoff level of anti-Müllerian hormone(AMH)which could help with the di-agnosis of polycystic ovary syndrome(PCOS)in adults,and to analyze the risk factors of metabolic syndrome(MS).Methods:A retrospectively analyzed 426 PCOS patients(PCOS group)and 205 healthy controls aged 20-39 years from the Health Checkup Center of the Gynecological Endocrine Center,Hunan Maternal and Child Health Hospital from January 2021 to December 2023.AMH diagnostic validity was estimated by receiver operating characteristic(ROC)curves.Patients were subgrouped into PCOS combined metabolic syndrome group(MS-PCOS)and the uncomplicated MS group(UMS-PCOS)according to metabolic status.Multivariate Logistic regression analysis was performed to determine the risk factors for MS in PCOS patients.Results:The serum AMH level was higher in PCOS group than that in the control group(8.42±3.71 ng/ml vs.2.99±0.94 ng/ml,P＜0.001).AMH cutoff for the diagnosis of PCOS was determined as≥4.87 ng/ml on ROC analysis,and the area under the curve is 0.981 with 92.7％sensitivity and 94.6％specificity.The prevalence of MS was 18.3％(78 ca-ses)in PCOS group.Subgroup analysis showed that MS-PCOS patients had higher waist circumference,BMI,fasting glucose,dyslipidemia,hypertension(BP＞130/85 mmHg),and hormone related index androgen level,but lower AMH vs.UMS-PCOS.Multivariate Logistic regression analysis identified insulin resistance(OR 39.17,95％CI 9.33-164.48),BMI ≥24 kg/m2(OR 3.72,95％CI 1.86-7.45),and hyperandrogenism(OR 2.56,95％CI 1.34-4.89)as independent risk factors of MS.AMH was negatively associated with MS,a single-unit increase in AMH was associated with an 17％decrease in odds of MS(OR 0.83,95％CI 0.73-0.95,P=0.006).Conclusions:Serum AMH levels were significantly higher in adult PCOS patients,with an optimal diagnostic threshold of 4.87 ng/ml.Hyperandrogenism and low AMH levels may predict a higher risk of MS,in addition to metabolism-related factors.

The clinical data, laboratory test, and gene mutations were collected from a family with pseudohypoaldosteronism type II(PHA2). The proband, aged 1 year and 7 months, presented with hyperkalemia(6.69 mmol/L; reference range 3.5-5.3 mmol/L), blood pressure of 110/68 mmHg(normal<106/61 mmHg, 1 mmHg=0.133 kPa), blood chloride of 111.5 mmol/L(reference 99-110 mmol/L), blood HCO 3- of 17.1 mmol/L(reference 22-29 mmol/L), estimated glomerular filtration rate of 128.5 mL·min -1·(1.73 m 2) -1[>90 mL·min -1·(1.73 m 2) -1], and blood renin concentration of 0.30 μIU/mL(reference 4.2-45.6 μIU/mL). The mother and maternal grandfather also exhibited normal renal function with hyperkalemia, hypertension, hyperchloremia, metabolic acidosis, and low renin. Genetic testing revealed a heterozygous missense mutation(c.1685A>G, p. E562G) in exon 7 of the no-lysine kinase 4(WNK4) gene. Treatment with hydrochlorothiazide was effective. Literature review comparing this E562G pedigree with other WNK4 variants suggested clinical heterogeneity of WNK4 mutations. For unexplained hyperkalemia, especially with concurrent hypertension, PHA2 should be considered early for genetic screening to prevent misdiagnosis or delayed diagnosis.

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.

Objective To evaluate the efficacy of different interventions to the extra cranial lesions in acute ischemic stroke(AIS)due to anterior tandem lesions(TL)on reperfusion.Methods As a multi-center,cross-sectional study,AIS due to anterior TL receiving mechanical thrombectomy(MT)were retrospectively collected.Interventions to the extra-cranial stenosis were recorded.Post-procedural reperfusion was assessed using the modified thrombolysis in cerebral infarction(mTICI)score.Complete revascularization was defined as mTICI 3 and good revascularization was defined as mTICI 2b/3.The relationship between different extra-cranial intervention regi-mens and rate of re-vascularization was compared.Results Totally 117 patients were included with 92.3% reaching good recanalization and 63.2% reaching complete re-canalization.There was no significant difference in good re-canalization rates among various extra-cranial intervention regimens.The rate of complete re-canalization was significantly higher in patients receiving endovascular therapy(P＜0.05)and there was significant difference among various endovascular treatment regimens(P＜0.01):acute balloon angioplasty only group presented the highest rate of complete re-canalization(100.0% ),followed by acute stenting only group(80% ),acute stenting+balloon angioplasty group(73.7% )and conservative treatment group(54.3% ).Conclusions Endovascular inter-vention to extra-cranial stenosis contributes to complete re-canalization in AIS due to anterior TL receiving MT,and acute balloon angioplasty seems to be quite effective than acute stenting.

Objective:To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs.Methods:An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-? t test was used for pairwise comparison. Results:ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2 +/+), heterozygous mutant (ALDH2 +/-), and homozygous mutant (ALDH2 -/-), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group ( P ?

Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.