In order to adapt to the requirements of modem medical knowledge and skills for higher medical workers,and to cultivate medical students' molecular medicine quality and comprehensive ability,Weifang Medical University broke the boundaries of disciplines and constructed experimental course group in molecular medicine based on the ideas of curriculum group construction.Molecular medical knowledge was integrated into the teaching process of experimental course group,experimental teaching content system was reasonably integrated and optimized,high quality teaching team was set up,multi-level experimental teaching platform was built and student-centered teaching mode was implemented to explore the experimental teaching approach which helped medical students to form systematic molecular medicine knowledge structure and ability structure.

Objective To investigate the relationship between CYP3A5 gene polymorphism and tacrolimus concentration/dose ratio in children living donor liver transplantation and the correlation with clinical efficacy,for the relatives living donor liver transplantation in children tacrolimus individualized medication providing reference indicators.Methods Peripheral blood samples were collected from children with relatives living donor liver transplantation in the center of liver transplantation,the genotype of CYP3A5 was determined by polymerase chain reaction (PCR)/pyrophosphate sequencing,The dosage of tacrolimus and blood concentration,liver and kidney function and other related indicators were measured within 3 months after operation According to genotypes,the children can be divided into gene expression group (CYP3A5 *1/*1 and CYP3A5 *1/*3) and non-expression group (CYP3A5*3/*3).The drug concentration (C0),tacrolimus dose / body weight (D/W) ratio,drug concentration/dose (C0/D) ratio of each genotype at 1 day,3 d,5 d,7 d,14 d,28 d,2 months and 3 months after administration and the genotype at the time point on liver and kidney function was carried out statistics.Results Among the 80 cases,36 cases (45.0％) were CYP3A5*3/*3,37 cases (46.2％) were CYP3A5*1/*3,7 cases (8.8％) were CYP3A5*1/*1.CYP3A5 gene expression group reached a therapeutic concentration range (C0 ＞ 8 μg/L) than the gene non-expression group takes longer time.There was no significant difference in CYP3A5 gene expression group between the non-expression group on the initial dose (P＞ 0.05);CYP3A5 gene expression group than the non-expression group,tacrolimus C0 within 1 month after operation were statistically significant.CYP3A5 gene expression group than the non-expression group,tacrolimus D/ W in addition to the first day after surgery,other time points were statistically significant (P＜0.05).CYP3A5 gene expression group than the non-expression group,C0/D at the above time points were statistically significant (P＜0.05);There were no significant differences in liver and kidney function between the two genotypes (P ＞ 0.05),but there was significant difference in the alkaline phosphatase.Conclusion CYP3A5 gene expression in children than non-expression group of children need higher doses to reach the therapeutic drug concentration;CYP3A5 gene polymorphism had significant effects on early tacrolimus C0,D/W and C0/D values;CYP3A5 gene polymorphism is instructive for the administration of tacrolimus in children with living donor liver transplantation,CYP3A5 gene type tests should be regular,improve efficacy and reduce the incidence of adverse reactions.

OBJECTIVETo summarize the clinical features of those Duchenne and Becker muscular dystrophy (DMD and BMD) patients who are complicated with epilepsy, and try to analyze the genotype- phenotype correlation.

METHODBy a retrospective analysis of 307 patients with DMD and BMD who attended Peking University First Hospital from February 2006 to September 2014,7 patients complicated with epilepsy were identified and their clinical data were collected. The possible mechanism of epilepsy in DMD and BMD patients was proposed after analyzing the genotype-phenotype correlation.

RESULT(1) Among 307 DMD and BMD patients, 7 cases had epilepsy, the prevalence was 2. 28%. (2) The age of onset of epilepsy ranged from 8 months to 11 years. Focal seizure was the most common seizure type (6 cases) , while other seizure types were also involved, such as generalized tonic-clonic seizure. As to epilepsy syndromes, 1 boy was diagnosed as benign childhood epilepsy with centrotemporal spikes (BECT). Six patients were treated with 1 or 2 types of antiepileptic drugs and seizures were controlled well. On follow-up, 6 of the 7 children had normal mental development, while the remaining 1 patient was diagnosed as mild mental retardation. (3) DMD gene mutations of all 7 patients were analyzed. Exons deletions were found in 6 cases while point mutation was found in 1 case.

CONCLUSIONThe prevalence of epilepsy in DMD and BMD patients was higher than the prevalence in normal population. The age of onset of epilepsy varies, and focal seizure may be the most common seizure type. Some patients may also present as some kind of epilepsy syndrome, such as BECT. In most patients, seizures can be controlled well by 1 or 2 types of antiepiletic drugs. No clear correlation was found between genotype and phenotype in DMD and BMD patients who were complicated with epilepsy, probably due to limited number of cases.

Anticonvulsants ; therapeutic use ; Child ; Epilepsy ; complications ; drug therapy ; epidemiology ; Exons ; Genotype ; Humans ; Intellectual Disability ; etiology ; Male ; Muscular Dystrophy, Duchenne ; complications ; genetics ; Mutation ; Phenotype ; Prevalence ; Retrospective Studies ; Seizures ; Sequence Deletion

Objective To summarize the clinical features of 22 probands diagnosed with congenital muscular dystrophy (CMD),and to provide genetic counseling and prenatal diagnosis for 23 fetuses of these pedigrees.Methods Data of 22 CMD patients who were treated in the Pediatric Department of Peking University First Hospital during October 2006 to March 2016 were analyzed.Informed written consents for participation in this study were obtained from the parents or guardians.Prenatal diagnosis was performed using DNA samples extracted from fetal villus cells of 12 cases at 11-13 gestational weeks and amniotic fluid of 11 cases at 18-22 gestational weeks.Direct DNA sequencing by polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) were used to detect CMD-related gene mutations.Linkage analysis of short tandem repeats (STRs) was used to identify maternal blood contamination and biological parents.Results Thirteen out of the 22 probands with CMD were diagnosed with congenital muscular dystrophy type 1 A (MDC1A),and all of them carried compound heterozygous mutations in LAMA2 gene.Prenatal diagnosis of 13 fetuses from these pedigrees found that four fetuses were wild-type,seven were heterozygotes and two carried the same mutations as their proband.Three probands with LMNA-related congenital muscular dystrophy (L-CMD) carried de novo mutations in LMNA gene.In these pedigrees,two fetuses were wild-type and one whose mother was mosaicism carried the same mutations as the proband.One proband with Ullrich congenital muscular dystrophy carried compound heterozygous mutations in COL6A2 gene and the fetus of the same pedigree was wild-type.Five probands were diagnosed with α-dystroglycanopathies.And among them,two cases of muscle-eye-brain disease (MEB) carried compound heterozygous mutations in POMGnT1 gene and the fetuses of the two peidgrees were heterozygotes;one case of congenital muscular dystrophy type 1C (MDC1C) had compound heterozygous mutations in FKRP gene and the fetus carried the same mutations;one patient diagnosed with POMGnT1-related congenital muscular dystrophy with mental retardation (CMD-MR) carried compound heterozygous mutations in POMGnT1 gene,and the fetus was positive for the same mutations;one proband with POMT1-related CMD-MR was positive for compound heterozygous mutations in POMT1 gene and the results of prenatal diagnosis for two fetuses of this pedigree showed that the first fetus had the same mutations as the proband,while the second was heterozygote.Conclusions No effective therapeutic method is available for CMD.Therefore,accurate genetic counseling and prenatal diagnosis are necessary to prevent CMD child from birth.

Objective To investigate the relationship between the ratio of neutrophils to lymphocyte and prehypertension and its clinical significance. Methods In May 2015,three thousand one hundred and twenty-six subjects who underwent physical examination in Tangshan People's Hospital Health Examination Center were enrolled in the study. 120 cases of pre hyperton were selected as the observation group,and 120 with normal blood pressure were used as the control group. The neutrophils and lymphocyte counts of the subjects were detected. The relationship among the two groups of test indicators,the ratio of neutrophils to lymphocyte counts and blood pressure was analyzed. Results The ratio of neutrophil and lymphocytes in the observation group was (2. 28± 0. 39), significantly higher than that in the control group ( 1. 41 ± 0. 32) ( t＝ 1. 196 P ＝0. 028). According to the different ratio of neutrophils / lymphocytes,the patients were divided into 3 groups,group A (1. 12 ± 0. 23), group B ( 1. 73 ± 0. 08), group C ( 2. 57 ± 0. 39), aling with the ratio increasing, the blood pressure increased,the systolic blood pressure of group A,B,C was (115±9) mmHg,(117±11) mmHg,(128 ±6) mmHg,respectively. The difference was statistically significant (F＝4. 404,P＝0. 013),the diastolic blood pressure of group A,B,C was (73±5) mmHg,(78±7) mmHg,(86±4) mmHg,respectively. The difference was statistically significant (F＝4. 553,P＝0. 027). Multivariate Logistic regression analysis showed that the ratio of neutrophils to lymphocytes was affected by systolic blood pressure,blood glucose,high density lipoprotein,BMI and triglyceride. Conclusion There is correlation between the ratio of neutrophil to lymphocyte and prehypertension, suggesting that inflammation may be involved in the occurrence and development of hypertension.

Objective To provide a reference for the individualized medication of tacrolimus in children after living related liver transplantation,according to the effect of CYP3A5 genotyping on the concentration/dose ratio of tacrolimus in children with living related liver transplantation.Methods Peripheral blood samples were collected from children with living related liver transplantation in the transplant center.The CYP3A5 genotype was determined by polymerase chain reaction (PCR)pyrosequencing.Related indicators such as tacrolimus dose and concentration in children with living related liver transplantation were collected within 3 months after operation.According to the donor/receptor genotype,the donor/receptor expression group,the donor/receptor single expression group,and the donor/receptor non-expression group were set up.Tacrolimus concentration/dose (C0/D) ratio was statistically analyzed at 5th day,7th day,14th day,28th day,2nd month and 3rd month after administration.Results Among the 76 patients,there were 21 patients (27.63％) in CYP3A5 donor/receptor non-expression group,27 patients (35.53％) in donor/receptor single expression group,and 28 patients (36.84％) in the donor/receptor expression group.The time to the target concentration range (C0＞8 ng/mL) in CYP3A5 donor/receptor expression group was longer than in donor/receptor single expression group and donor/receptor non-expression group.Except for the individual time points,there were significant differences between CYP3A5 donor/receptor expression group and donor/receptor non expression group,or between donor/receptor non-expression group and donor/receptor single expression group,or between donor/receptor expression group and donor/receptor single expression group at rest time points (P＜0.05 for all).Conclusion In the CYP3A5 donor/receptor gene expression group,the higher dose was needed to reach the target concentration range than the gene single expression group and the donor/receptor non-expression group.Except for individual time points,there were significant differences in C0/D at rest different time points.Regardless of whether the donor or recipient contained the CYP3A5* 1 allele,C0/D was lower than the non-expressed type of the gene.Considering the polymorphism of the donor/receptor CYP3A5 gene,it was worthful for children with living related liver transplantation to allow the drug concentration to reach the therapeutic window as soon as possible and reduce organ rejection and adverse reactions.

Objective:To investigate the association between alcohol consumption and hypertension and SBP, DBP and the mediating effects of body mass index (BMI) and lipid level in occupational population, and provide reference for the intervention and prevention of hypertension.Methods:Based on the data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., the information about the demographic characteristics, behavior and lifestyle, blood pressure and lipids level of the participants were collected through questionnaire survey, physical examination and blood biochemical test. Logistic/linear regression was used to analyze the association between alcohol consumption and hypertension, SBP and DBP. The individual and joint mediating effects of BMI, HDL-C, LDL-C, TG, and TC were explored through causal mediating analysis. A network analysis was used to explore the correlation between alcohol consumption, BMI and lipid levels, and hypertension.Results:A total of 22 887 participants were included, in whom 1 825 had newly detected hypertension. Logistic regression analysis found that current/former drinkers had a 33% increase of risk for hypertension compared with never-drinkers ( OR=1.33, 95% CI:1.19-1.48). Similarly, alcohol consumption could increase SBP ( β=1.05, 95% CI:0.69-1.40) and DBP ( β=1.10, 95% CI:0.83-1.38). Overall, BMI and lipid levels could mediate the associations between alcohol consumption and hypertension, SBP and DBP by 21.91%, 28.40% and 22.64%, respectively. BMI and TG were the main mediators, and they were also the two nodes with the highest edge weight and bridge strength centrality in the network of alcohol consumption, BMI, lipid levels and hypertension. Conclusions:Alcohol consumption was associated with increased risk for hypertension, and BMI and TG were important mediators and key nodes in the network. It is suggested that paying attention to the alcohol consumption, BMI and TG might help prevent hypertension in occupational population.

Objective:To analyze the genomic characteristics and variations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) derived from an outbreak in inbound flight in Aug, 2022 in Beijing, and provide reference data for disease prevention and control and risk assessment.Methods:Fifty respiratory tract specimens from all cases in this outbreak were collected. The digital PCR (ddPCR) was used to determine the viral loads of the specimens. The full genome of the viruses were sequenced by Next-generation sequencing. Then analuses were performed on the genetic identity, variations and phylogenesis.Results:The median of viral loads in all 50 samples were 5.57×10 4 copies/ml and 5.85×10 4 copies/ml, for ORF1ab gene and N gene, respectively. A total of 46 SARS-CoV-2 genomes were obtained, which all belonged to Omicron/BA.5. Two genome clusters were observed, involving 21 and 7 cases, with a nucleotide sequence identities of 99.993% and 99.997%, respectively. Conclusions:The studied outbreak was composed of two main clusters and other individual cases with Omicron/BA.5 virus overseas.

Objective:To explore the diagnosis and treatment of transplanted renal artery stenosis(TRAS)in children.Methods:From January 2016 to August 2021, clinical data of 7 TRAS patients were collected.A definite diagnosis was confirmed by Doppler ultrasound and computed tomography angiography.Results:Patient age was significantly higher than donor age(11.9±3.7 vs 1.0±0.5 years, P<0.001); 5 patients had a widened diameter at stenotic grafted renal artery after intervention(1.98±0.47 vs 4.64±1.19 mm, P=0.002). A reduction in peak systolic flow velocity in stenotic segment of artery(463.3±90.6 vs 183.6±58.9 cm/s, P<0.001)and lower systolic blood pressure(137.2±15.5 vs 129.7±12.3 mmHg, P=0.029)were observed.Resistance index rose(0.38±0.22 vs 0.60±0.03, P=0.063). Significant difference of estimated glomerular filtration rate was observed at Week 4 post-operation as compared with pre-intervention.Two patients developed complications after intervention, including perirenal hematoma and stent-attached thrombus.Two patients were treated conservatively with a gradual increase in blood pressure and three antihypertensive drugs prescribed. Conclusions:Doppler ultrasound should be performed regularly after renal transplantation for detecting TRAS at an early stage in children.Interventional treatment is ideal for severe TRAS to improve perfusion and renal function.Clinicians should pay more attention to complications.

Objective:To clarify the M protein ( emm gene) types and drug susceptibility characteristic variations of Group A Streptococcus (GAS) in children in Beijing. Methods:The GAS strains isolated from throat swab samples of children diagnosed with scarlet fever and pharyngeal infection in scarlet fever etiology surveillance sentinel hospitals in 16 districts of Beijing in 2018, 2019 and 2021 were analyzed retrospectively.PCR amplification and sequencing were used for emm genotyping, and the minimum inhibitory concentrations (MIC) of 10 antibiotics were determined by the broth microdilution method.The data were analyzed using χ2 test and Fisher′ s exact method between groups. Results:A total of 557 GAS strains were collected, and 11 emm genotypes ( emm1, emm3, emm4, emm6, emm11, emm12, emm22, emm75, emm89, emm128, and emm212) were detected.Of 557 strains, 238 trains were of emm1 type (42.73%), 271 strains were of emm12 type (48.65%) and 48 strains were of other emm types (8.62%). The detection rates of emm1, emm12 and other emm type genes in 2018, 2019, and 2021 were [37.50% (105/280 strains), 57.14% (160/280 strains), 5.36% (15/280 strains)], [49.05% (129/263 strains), 39.54% (104/263 strains), 11.41% (30/263 strains)], and [28.57% (4/14 strains), 50.00% (7/14 strains), 21.43% (3/14 strains)], respectively.In children infected with emm12 in 2018 and 2019, there were more children under 6 years old than children over 6 years old (62.50% vs.46.88%, 46.36% vs.30.36%) (χ 2=7.182, 6.973; all P<0.05). Drug susceptibility testing results suggested that 225 randomly selected GAS strains were all 100.00% sensitive to 7 antibiotics including Penicillin, Levofloxacin, Meropenem, Linezolid, Cefotaxime, Cefepime and Vancomycin.The rates of resistance to Erythromycin, Tetracycline and Clindamycin were [88.57% (93/105 strains), 87.62% (92/105 strains), 86.67% (91/105 strains)], and [94.34% (100/106 strains), 94.34% (100/106 strains), 87.74% (93/106 strains)] in 2018 and 2019, respectively.The test strains were 100.00% (14/14 strains) resistant to the above 3 antibiotics in 2021.MIC 50 and MIC 90 values of Penicillin in 2018, 2019, and 2021 were (0.03 mg/L, 0.03 mg/L), (0.03 mg/L, 0.06 mg/L), and (0.06 mg/L, 0.06 mg/L), respectively.Among 225 GAS strains, 207 strains had drug resistance and were resistant to more than one drug.Specifically, 94.69% (196/207 strains) were resistant to Erythromycin, Tetracycline and Clindamycin.About 4.35% (9/207 strains) were resistant to both Erythromycin and Clindamycin.A total of 0.97% (2/207 strains) were resistant to Erythromycin and Tetracycline. Conclusions:The emm genotypes of GAS in children in Beijing are diverse in 2018, 2019 and 2021.The dominant genotypes are emm12 and emm1, and emm12 is the main epidemiological type.GAS strains maintain highly resistant to Erythromycin, Clindamycin and Tetracycline, and sensitive to Penicillin and other antibiotics.However, MIC 50 and MIC 90 of Penicillin shows an ascending trend.