Voltage-gated sodium channel α2-subunit gene related epilepsy with autism spectrum disorder: a case report / 中华神经科杂志

Objective:To summarize the clinical features and treatment of voltage-gated sodium channel α2-subunit (SCN2A) gene-related epilepsy.Methods:The clinical manifestion, video electroencephalography, head magnetic resonance imaging of a child diagnosed with epilepsy in Hebei Children′s Hospital were analyzed. Additionally, blood samples of the family were tested for the whole exome sequencing.Results:The boy aged 20 months,had been developed backward since childhood and accompanied by autism spectrum disorder manifestations. Seizures occurred at 19 months, manifested as isolated and clusters of spasms or generalized tonic seizures. The whole exome sequencing of the family revealed that the proband had c.4543C>T heterozygous mutation in the SCN2A gene, and both parents showed wild type. The effect of multiple anti-epileptic drugs on the children was not good, but the epilepsy was controlled after the final addition of perampane.Conclusions:The c.4543C>T heterozygous variant of SCN2A gene is the cause of disease in this child. This variant can cause epilepsy with autism spectrum disorder. The location and type of SCN2A mutations are strongly related with phenotypes, and a clear genetic etiology contributes to accurate treatment of children.

Efficacy of the modified gasless unilateral axillary approach endoscopic thyroid surgery in the treatment of papillary thyroid microcarcinoma / 中华内分泌外科杂志

Objective:To investigate the efficacy and safety of the modified gasless unilateral axillary approach (MGUAA) endoscopic thyroid surgery in treatment of papillary thyroid microcarcinoma (PTMC) .Methods:From Jan. 2019 to Dec. 2019, 90 patients receiving PTMC (cT1N0M0, cI stage, 8th, 2017 AJCC) therapy by modified gasless unilateral axillary approach endoscopic thyroid surgery (MGUAA group, n=41) , and conventional open thyroid surgery (OS group, n=49) were retrospectively analyzed. Ninety patients were enrolled in the study, including 14 males and 76 females,with the mean age (42.1±12.0) years.The effectiveness of central lymph node dissection (CLND) , the operation time, the types of operation, the amount of drainage, the duration of hospital stay, the related complications, the postoperative pain of neck and axillary and the cosmetic satisfaction were compared between the two groups.SPSS 25.0 statistical software was used for statistical analysis, the measurement data was expressed by ±s, paired t test was used to compare the measurement data between groups, and Chi-square test was used to campare the count date between groups. Results:The mean age (35.0±8.6) years and the amount of surgical bleeding (12.3±7.3) ml in the MGUAA group were significantly lower than those (48.1±11.1) years and (16.1±4.3) ml in the OS group ( P<0.01) , while the mean operation time (99.1±19.5) min, the mean amount of drainage (221.4±67.9) ml and the postoperative drainage tube placement time (5.0±0.8) days were significantly higher than those of (70.6±17.8) min, (98.3±63.7) ml and (3.8±1.0) days in the MGUAA ( P<0.01) . There was no significant difference in the number of lymph nodes of CLND or the duration of hospital stay between the two groups ( P>0.05) . In terms of surgical complications, the transient recurrent laryngeal nerve injury, the postoperative hematoma, the postoperative infection, and the lymphatic leakage had no significant difference between the two groups ( P>0.05) . The MGUAA group had significant advantages in avoiding the postoperative dysphagia in front of neck, the postoperative pain of neck, and cosmetic satisfaction over the OS group [ (0.0% vs 28.6%) , (14.6% vs 71.4%) , (1.1±0.3) score vs (2.4±0.5) score ( P<0.01) ]. Whereas in axillary area pain on the surgical side, the MGUAA group was inferior to the OS group ( P<0.01) . Conclusion:The modified gasless unilateral axillary approach endoscopic thyroid surgery is a feasible, safe and cosmetically operation for PTMC (cT1N0M0, cI stage, 8th, 2017 AJCC) .

Phenotypic and genetic analysis of a boy with inv dup del(8p) / 中华医学遗传学杂志

OBJECTIVE@#To delineate the nature and origin of a chromosomal aberration detected in a boy with mental retardation.@*METHODS@#The proband and his parents were subjected to routine G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis.@*RESULTS@#The karyotype of the proband was determined as 46, XX, add(8)(p23). No karyotypic abnormality was detected in either of his parents. SNP-array has identified a 34.9 Mb duplication at 8p23.1q11.1 and a 6.78 Mb microdeletion at 8p23.1pter in the proband. No copy number variation was detected in either parent.@*CONCLUSION@#The child was diagnosed with 8p inverted duplication deletion syndrome, which might be induced by non-allelic homologous recombination between olfactory genes in the 8p23.1 region.

The expression and significance of peripheral lymphocyte immunity and humoral immunity in children with autoimmune encephalitis and children with mycoplasma encephalitis / 中国医师进修杂志

Objective:To investigate the expression level and significance of peripheral lymphocyte immunity and humoral immunity in children with autoimmune encephalitis and children with mycoplasma encephalitis.Methods:From July 2018 to July 2019, 52 children with autoimmune encephalitis (autoimmune encephalitis group) and 68 children with mycoplasma encephalitis (mycoplasma encephalitis group) in Hebei Children′s Hospital were enrolled, and 43 children with mycoplasma infection who were treated at the same time were selected as control group. Serum immunoglobulin (IgA, IgG, IgM) levels were detected using a fully automated biochemical analyzer, and peripheral T-lymphocyte subsets (CD 3+, CD 4+, CD 8+, CD 4+/CD 8+) levels were measured using flow cytometry. The receiver operating characteristic (ROC) curve was used to analyze the clinical differential diagnostic value of serum immunoglobulin and T lymphocyte subsets indicators for autoimmune encephalitis and mycoplasma encephalitis. Results:The levels of serum IgA, IgM in three groups had significant differences ( P<0.05); the levels of serum IgA, IgM in mycoplasma encephalitis group were significantly higher than those in autoimmune encephalitis group and control group [(1.64 ± 0.56) g/L vs. (1.23 ± 0.48),(0.82 ± 0.25) g/L; (1.81 ± 0.45) g/L vs. (1.56 ± 0.48), (1.12 ± 0.34) g/L]( P<0.05); the level of IgG in three groups has no significant difference ( P>0.05). The levels of CD 4+,CD 8+ in mycoplasma encephalitis group were significantly higher than those in autoimmune encephalitis group and control group [(31.21 ± 3.86)% vs. (28.76 ± 3.57)%, (26.58 ± 3.49)%; (26.86 ± 1.89)% vs. (25.90 ± 2.16)%, (24.71 ± 2.46)%]( P<0.05); the level of CD 4+/CD 8+ in three groups has no significant difference ( P>0.05). The areas under the curve of serum IgA, IgM, CD 3+, CD 8+, CD 4+ and five combined diagnosis were 0.971, 0.835, 0.833, 0.631, 0.706 and 1.000. The optimal critical values were 1.255 g/L, 1.465 g/L, 57.435%, 26.456%, 29.750% and 1.858. The sensitivity was 100.0%, 64.7%, 95.6%, 92.6%, 69.1% and 100.0%, and the specificity was 95.6%, 57.0%, 57.1%, 23.4%, 36.4% and 100.0%. Conclusions:The expression levels of serum IgA, IgM and peripheral serum CD 3+, CD 4+ and CD 8+ in children with autoimmune encephalitis are significantly lower than those in children with mycoplasma encephalitis, and IgA, IgM, CD 3+, CD 8+ and CD 4+ has high differential diagnosis value.

A case of SBBYSS syndrome caused by KAT6B gene variant / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and molecular genetics features of a family affected with Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS).@*METHODS@#High-throughput sequencing was used to detect copy number variations (CNVs) and pathogenic variant within the whole exome of the affected child.@*RESULTS@#No pathogenic CNV was found in the child, while exome sequencing identified a heterozygous c.3367_c.3370delAGAA (p.Arg1123Argfs*6) frameshifting variant in the exon 16 of the KAT6B gene. The same variant was not found in either parent.@*CONCLUSION@#The c.3367_c.3370delAGAA (p.R1123Rfs*6) probably underlies the disease in the affected child. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.

Kleefstra syndrome 1 and ring chromosome 9 in a case / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and molecular genetic characteristics of patient with Kleefstra syndrome 1.@*METHODS@#Clinical data, chromosomal karyotype and whole genome copy number variations (CNVs) of the patient were analyzed.@*RESULTS@#The patient was found to have a karyotype of 45,XX,-9[4]/46,XX,r(9)(p24q34)[56]. Whole-genome CNVs detection revealed that she has carried a heterozygous deletion of approximately 670 kb at 9q34.3, which encompassed the entire EHMT1 gene. The region is strongly associated with Kleefstra syndrome (1/9q telomere deletion). In addition, the patient also had heterozygous deletion of 9pter, which may predispose to formation of ring chromosome 9.@*CONCLUSION@#The child was diagnosed with Kleefstra syndrome type 1 in conjunct with ring chromosome 9.

Therapeutic drug monitoring of mizoribine in renal transplant recipients / 中国药理学通报

Mizoribine(MZR), as an orally prescribed immunosuppressive agent, has been applied in the prevention of rejection after kidney transplantation.MZR requires individual dosing due to the variation of bioavailability.However, therapeutic drug monitoring (TDM) of MZR is not well developed in China, as compared to other clinically used immunosuppressive agents.To our knowledge, this is the first TDM review of MZR.Pharmacokinetic characteristic, concentration determination methods and sample selection of MZR were summarized, also the rational therapeutic window was proposed.Furthermore, gene polymorphism and population pharmacokinetics of MZR were estimated.This review will provide reference for TDM-based individual dosing of MZR in renal transplant recipients.

Correlation Analysis of Baseline Antimullerian Hormone Level and Live Birth Rate of Fresh Embryo Transfer Cycles and Frozen Embryo Transfer Cycles / 中山大学学报(医学科学版)

[Objective]To investigate the relationship of baseline antimullerian hormone(AMH)and live birth rate of IVF/ICSI and further explore the prognostic effect of AMH on live birth rate.[Methods]All non-polycystic ovary patients who underwent their first embryo transfers in our unit and had basal serum AMH evaluated between 2010 and 2015 were evaluated in this retrospective study. Patients were grouped according to their AMH level,i.e. low AMH group with AMH less than 1.1 ng/mL(n = 485),middle AMH group with AMH between 1.1 ng/mL and 7.0 ng/mL (n = 1 989),and high AMH group with AMH higher than 7.0 ng/mL (n=468). For age subgroup analysis,patients were stratified as follow:group A(age≤29 years),group B(30~34 years),group C(35~39 years)and group D(over 40 years). We compared clinical outcomes between AMH groups in different age groups usingunivariate and multivariate analysis. ROC analysis was utilized to assess predictive value of AMH on live birth rate.[Results](1)In both fresh and frozen embryo transfers,baseline AMH was significantly related to clinical outcomes. The lower AMH was,the lower implantation rate,clinical pregnancy rate,and live birth rate. However,higher miscarriage rate was observed. All difference reached statistically significant.(2)In age subgroup analysis,we demonstrated AMH was related to live birth rate in patients in group A,B, and C,regardless of fresh or frozen embryo transferred. In those over 40 years,AMH was related to live birth rate in frozen cycles (P < 0.05)but not fresh cycles(P = 0.092). The further multivariate analysis confirmed the above results after controlling po?tential confounding variables.(3)The AUC of ROC analysis for AMH predicting live birth rate were 0.647,0.633 for fresh and fro?zen cycles respectively.[Conclusion]Baseline AMH as one of excellent ovarian reserve markers ,was significantly related to live birth rate in fresh or frozen cycles. Baseline AMH was an independent prognostic factor of live birth rate,but its predictive value on live birth rate was of limited clinical value.

Impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese renal transplant recipients / 中国药理学通报

Aim To investigate the impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese stable renal transplant re-cipients. Methods Pharmacokinetics of once daily-ta-crolimus( tac-q. d. ) and twice daily-tacrolimus( tac-b. i. d. ) were determined by CLIA, CYP3A5 genotype was measured by PCR-RFLP. Each 10 patients receiv-ing tac-q. d. and tac-b. i. d. respectively were en-rolled, and each 5 patients receiving tac-q. d. were matched to poor metabolizer ( PM ) and extensive me-tabolizer ( EM ) group respectively according to CYP3A5 genotypes. Results AUC0~24 h for tac-q. d. was 1. 78 folds higher than AUC0~12 h for tac-b. i. d. , and dose-adjusted C0 was 40% lower for tac-q. d. than for tac-b. i. d. There were no significant differences for other parameters between the two groups; Cmax, AUC0~24 h and C0 were 1. 75, 1. 96 and 2. 49 folds higher for PM than for EM, and dose-adjusted Cmax, AUC0~24 h and C0 were 1. 80, 2. 34 and 2. 64 folds higher for PM than for EM. There were good correla-tions between AUC0~24 h and C0 for tac-q. d. Conclu-sion Conversion from tac-b. i. d. to tac-q. d. results in requirement of increased tacrolimus dose and detec-tion of CYP3A5 genotype, which is necessary for ensu-ring C0 in the range of therapeutic window.

Nuclear receptors as drug targets in cholestasis / 中国药理学通报

Drug for cholestasis therapy is extremely limited.Ur-sodeoxycholic acid is currently the only FDA approved drug to treat primary biliary cirrhosis,whereas its efficacy is limited to early stage of the disease.Therefore,developing novel drugs re-presents a major goal for both pharmaceutical industry and aca-demic researchers.Targeting nuclear receptors in cholestasis is an intriguing approach since these receptors are critically in-volved in the regulation of bile acid homeostasis.This review summarizes the roles of individual nuclear receptors in cholestasis and evaluates their potential clinical application.

Influence of neuregulin-1 on pacing threshold of low voltage area in rats after myocardial infarction / 心血管康复医学杂志

Objective:To explore the influence of neuregulin- 1 (NRG-1)intervention on pacing threshold of low voltage area in rats after myocardial infarction.Methods:Myocardial infarction model of rat was established via an-terior descending coronary artery ligation.The 34 rats with myocardial infarction were randomly and averagely di-vided into two groups:NRG-1 group (received NRG-1peritoneal injection)and control group (received peritoneal injection of normal saline of the same volume).After two weeks,pacing thresholds were tested in low voltage area related with infarct in rats after myocardial infarction,and Cx43 (an integral membrane protein of the connexin family)expression was measured in low voltage area.Results:After drug intervention two weeks,compared with control group,there was significant reduction in pacing threshold [(1.466±0.503)V vs.(0.7167±0.194)V,P =0.002]in NRG-1 group;there was significant rise in Cx43 expression [(0.30±0.15)vs.(0.95±0.20),P <0.001] in low voltage area in NRG-1 group.Conclusion:Neuregulin-1 significantly reduces pacing threshold of low voltage area in rats after myocardial infarction,the mechanism may be related to increase Cx43 expression and improve e-lectrical conductivity of myocardial cells.

The study of long-term ventricular late potential in the acute myocardial infarction / 中国实用内科杂志

Objectives This study aimed at finding cut if reperfusion could be identified by long term VLP,using digital Holter ECG.Methods 24 hour 3 channel digital Holter recorders were performed on 38 patients with AMI before thrombolytic therapy,then the patients were divided into successful reperfusion group and unsuccessful reperfusion group.Every parameter was comparied between the two groups.Results VLP parameters showed a gradual improvement in the acute phase of MI in patients with successful reperfusion compared with those of unsuccessful reperfusion and that a significant difference between these two groups became evident from 2～3 hour after thrombolysis.Conclusions Our investigation certifies that successful reperfusion reduces VLP positive rate significantly 2～3 hours after thrombolysis.Thus,long term ventricular late potential may be helpful for identification of the reperfusion in AMI patients.In the mean time,Our study is performed before the formation of myocardial fibrous scar in AMI patients,it breaks up the traditional concept that VLP only developed from the formation of myocardial fibrous scar.