The development of precision medicine in 21st century has accelerated a new area of medicine,bringing a precise project of diagnosis and treatment.The new techniques for genetic diseases including next generation sequencing and copy number variation detection technology have facilitated the diagnosis and treatment of genetic and rare diseases in children's neural system,providing a new directed therapies especially for creatine deficiency syndromes,pyridoxine dependent epilepsy,glucose transporter type 1 deficiency syndrome,malignant migrating partial seizures in infancy,GRIN2A-related early-onset epileptic encephalopathy,KCNQ2-related epilepsies.With the new area of precision medicine arrival,an epoch-making revolution for the diagnosis and treatment of genetic and rare diseases in children's neural system is coming towards us.

Objective To study the clinical features and gene mutations of early - onset epileptic encephalo-pathy(EOEE)of unknown causes and to identify pathogenic mutations of EOEE by next generation sequencing. Methods The clinical data of 62 cases diagnosed with unexplained EOEE between June 2013 and June 2015 were ob-tained and analyzed. Specimens were collected from the selected children and their parents. Next generation sequencing was used to detect epilepsy - related genes,and Sanger sequencing was performed to verify the results and confirm the source of the parents,further to identify suspected pathogenic mutations of EOEE. Results Among 62 cases with unex-plained EOEE,37 cases(61% )were diagnosed as non - specific EOEE,17 cases(27% )with West syndrome,6 ca-ses(10% )with Dravet syndrome,1 case(1% )with Ohtahara syndrome,1 case(1% )with early myoclonic epileptic encephalopathy. The pathogenic mutations were not detected among 17 cases with West syndrome and the early myoclonic epileptic encephalopathy. Among 37 cases with non - specific EOEE,suspected pathogenic mutations were detected in 7 cases. Three cases of missense mutations for PCDH19 gene,1 case of frame - shift mutation and 1 case of splice site mutation for CDKL5 gene,1 case of denovo nonsense mutation for KCNQ2 gene,and 1 case of missense muta-tion for GRIN2A gene were detected. Among 6 children with Dravet syndrome,2 cases of frame - shift mutations and 1 case of missense mutation for SCN1A gene were detected,of which 2 cases were of frame - shift mutations,1 case was denovo mutation,1 case of missense mutation for SCN1A gene and 1 case of missense mutation for SCN1A combined with SCN9A gene were detected. One case of denovo nonsense mutation for STXBP1 gene was detected. After treatment, 22 cases with clinical seizures were under control,and 40 cases were out of control. Conclusions The clinical pheno-types for children with unexplained EOEE were varied. SCN1A,SCN9A,STXBP1,PCDH19,CDKL5,KCNQ2 and GRIN2A genes detected in China are in accordance with those reported internationally and some gene sites are denovo mutations which have not been reported. The SCN9A gene may be the new pathogenic mutation for Dravet syndrome. And the KCNQ2 gene nonsense mutation may be the lethal mutation.

Hemorrhage ; genetics ; Humans ; Mutation ; Recurrence ; alpha 1-Antitrypsin ; genetics

Codon, Nonsense ; Epilepsy ; genetics ; Humans ; KCNQ2 Potassium Channel ; genetics

Objective:To summarize our clinical experience in the treatment of aortic root aneurysm by aortic valve sparing root replacement.Methods:From May 2017 to October 2019, a total of 20 patients with aortic root aneurysm underwent aortic valve sparing root replacement by reimplantation method. There were 17 males and 3 females, with an average age of(35.6±15.8) years(12-63 years). There were 11 cases of Marfan syndrome, 5 cases of bicuspid aortic valve, and 1 case of redo operation. The preoperative diameter of ascending aorta was(40.6±9.7)mm, the diameter of aortic sinus was(52.2±9.2)mm, and the diameter of aortic valve ring was(27.1±3.6)mm. There were 10 cases of no or mild regurgitation, 5 cases of moderate regurgitation and 5 cases of severe regurgitation. In the whole group of patients, the root replacement of aortic valve was retained by reimplantation, and the artificial graft were selected as: 26, 28 and 30mm straight vessels, 1, 3 and 6 cases, respectively, 26 and 28mm artificial graft with valsalva sinus, 4 and 6 cases, respectively. During the operation, aortic valve cusp repair was performed in 6 cases, such as plication of the free margin( 4 cases), decalcification(1 case) and raphe release(1 case).Results:None of the patients died in hospital or underwent rethoracotomy for hemostasis. During the operation, the duration of CPB time was(171.0±25.6) minutes and the duration of cross-clamp time was(134.0±23.2) minutes. There were 12 cases of aortic valve regurgitation and 8 cases of mild regurgitation. The mean follow-up was(15.1±9.8) months(4-33 months). During the follow-up period, there were 2 cases with moderate aortic regurgitation no need reoperation, while the rest of the patients had no or mild regurgitation. There are no patients undergoing reoperation. During the follow-up, 1 patient suffered coronary artery embolism in left circumflex artery and recovered after medicine treatment.Conclusion:Reimplantation with aortic valve sparing root replacement is safe and effective in the treatment of aortic root aneurysm, and the early and mid-term follow-up results are satisfactory, which can avoid anticoagulation-related complications and is suitable for young patients.

This study is to explore the interventional effects of fluvastatin on anti-beta2GPI/beta2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-beta2GPI/beta2GPI, then the TF expression on THP-1 cells was detected by real-time quantitative PCR (RT-qPCR) or TF activity was detected by kit. TNF-alpha mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-kappaB p65 and inhibitory protein of NF-kappaB (IkappaB-alpha) were measured by Western blotting. The results suggested that the expression of TF and TNF-alpha on THP-1 cells was significantly up-regulated with treatment of anti-beta2GPI/beta2GPI complex (100 mg x L(-1)), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mg x L(-1)) could decrease TF (mRNA and activity) expression and the level of TNF-alpha (mRNA and protein) in THP-1 cells with anti-beta2GPI/beta2GPI complex. The expression of TF and TNF-alpha was shown in a concentration-dependent manner. Moreover, anti-beta2GPI/beta2GPI complex could downregulate IkappaB-alpha levels and increase the levels of phospho-NF-kappaB p65. And these effects of anti-beta2GPI/beta2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-kappaB signal transduction pathway, thereby inhibit the effects of anti-beta2GPI/beta2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-alpha.

Objective:To investigate the application of drug utilization evaluation( DUE) as a kind of clinical pharmacy work model in the antibacterial drug special rectification. Methods: Following the steps of DUE schedule,retrospective method was conducted to collect the data of the use of vancomycin in one institution and the model of clinical drug use was improved by the evaluation result. Re-sults:The rationality of vancomycin use was improved in the institution. The index of drug use reasons and key disease course indica-tors was improved significantly. The qualification rate of indications and drug indications was increased from 79. 5% to 95. 0%,and the qualification rate of antibacterial drugs classification management was increased from 63. 3% to 92. 7%. The qualification rate of dosing frequency was increased from 72. 5% to 96. 0%. Conclusion:As a program for continual improvement of new clinical pharmacy work mode and medical care quality,the mode plays an important role in the institution and improves the rational use of vancomycin.

Objective:To investigate the relationship of CYP2C19 gene polymorphisms and clopidogrel resistance in the patients with coronary atherosclerotic heart disease ( CAHD) accepted percutaneous coronary intervention ( PCI) in Chinese Han population from north Sichuan. Methods:The patients with CAHD undergoing PCI were recruited. The fluorescence in situ hybridization ( FISH) technology was used to detect the CYP2C19 gene polymorphisms in all the patients. According to the different genotypes, the patients were divided into different groups. The platelet maximum aggregation rate ( MAP) induced by ADP was detected before and after the administration of clopidogrel. Results:The 110 patients were divided into three groups:52(47. 3%) patients were divided into the fast metabolism group, 42(38. 1%) patients were in the moderate metabolism group and 16(14. 6%) patients were in the slow metab-olism group. Before the administration, there was no significant difference in the basic values of the platelet aggregation rate among the groups with various metabolism type (P=0. 873). In 24 hours after the administration of 300mg clopidogrel, there was notable differ-ence in the platelet aggregation rate (17. 74% ± 5. 87% vs 21. 44% ± 8. 71% vs 27. 05% ± 8. 83%, P=0. 044) and the decrease de-gree (20. 08% ± 5. 94% vs 18. 87% ± 4. 72% vs 11. 54% ± 2. 94%, P=0. 01) among the three groups. The moderate metabolism group and slow metabolism group had higher MAP with lower decrease degree than the fast metabolism group. Totally 21 patients (19. 1%)were with CR, and among them, 2 patients (3. 8%) were in the fast metabolism group,12 patients (28. 6%) in the moder-ate metabolism group and 7 ones (43. 8%) in the slow metabolism group, and the difference of CR distribution among the three groups was significant (P<0. 001). The moderate metabolism group and slow metabolism group were more likely to have clopidogrel resist-ance, especially the slow metabolism group. Conclusion: There is a certain relationship of CYP2C19 gene polymorphisms and clopi-dogrel resistance in the patients with CAHD accepted PCI in Chinese Han population from north Sichuan, and those with slow metabo-lism genotype are more likely to have clopidogrel resistance with reduced efficacy.

Objective To investigate the regulation effect of hepatocyte nuclear factor (HNF) 1α on the gene expression profile and the signal pathways in HuH7 cells.Methods The expression of HNF1α was increased or decreased in HuH7 cells by Lenti-virus carrying HNF1α or shHNF1α.The expression profile of the cells after treated was examined by microarray technology.The difference expressed gene regulated by HNF1α were screened and the pathway was analyzed with DAVID software and related analysis system.The regulation effect of HNF1α on transforming growth factor (TGF)β signal pathway was detected by reporter gene test and the regulation role of HNF1α on related genes of TGFβ signal pathway was determined by real-time polymerase chain reaction (PCR) and Western blotting assay.Results The expression of HNF1α in HuH7 cells was significantly up-regulated by Lenti-virus carrying HNF1α gene (Lenti-HNF1α) and which was down regulated by Lenti-virus with shHNF1α gene (LentishHNF1 α).Expression profile analysis revealed that 339 genes were positively up regulated two times by HNF1α and 325 genes were negatively down regulated two times.Signal pathway analysis revealed that HNF1α regulated drug metabolism,biosynthesis of unsaturated fatty acids and glycolysis/gluconeogenesis metabolism signal pathways.Moreover,it also involved in the regulation of TGFβ、nuclear factor (NF)-κB and p53 tumor-related signal pathways.Furthermore,Luciferase reportor gene experiment indicated that up-regulated HNF1α could inhibit the activation of TGFβ signal pathway.And the results of real-time PCR and Western blotting verified that up-regulated HNF1α could inhibit TGFβ signal pathway related gene c-myc and TGFβ1 and then inhibited the activation of TGFβ signal pathway.Conclusion HNF1α broadly affects the gene expression profile and the tumor genesis and development related signal pathways in HuH7 cells,furthermore,HNF1α can inhibit the activation of TGFβ signal pathway.

Objective To evaluate the clinical value of CT scan in the diagnosis of tracheoesophageal groove lymph node (TEGLN) metastasis of thoracic esophageal carcinoma. Methods Forty-six patients with thoracic esophageal carcinoma underwent esophagectomy with three-field dissection (3FD) of the cervical, mediastinal, and abdominal lymph nodes. CT findings of TEGLN were compared with that of pathological findings. Results Among the 46 patients who underwent esophagectomy with 3FD, 14 (30%) were found to have TEGLN metastases. Of the 277 TEGLNs excised by operation, 16 were found to have metastases. Primary sites of the thoracic esophageal carcinoma with TEGLN metastasis in upper, middle, or lower portion were 66.67%, 22.86%, and 40%, respectively. The difference between each portion was not statistically significant. The thoracic esophageal carcinoma with TEGLN metastasis in T 1, T 2, T 3 and T 4 staging were 50.00%, 25.00%, 28.57%, and 100.00%, respectively. There was no statistically significant difference between each T staging. 18 TEGLNs were found in CT scans. The average diameter of them was 1cm (0.3～2.5 cm). Sensitivity and specificity of CT examination were 87.50% and 98.47%, respectively. Positive predict value and negative predict value were 77.78% and 99.23%, respectively. Conclusion In patient with thoracic esophageal carcinoma, nodules appeared in tracheoesophageal groove could be diagnosed as lymph nodal metastases. Low cervical and mediastinal CT scan should be a conventional examination, and it was the basis of the radiation therapy plan. Dissection of TEGLN was very important for patient of thoracic esophageal carcinoma, but if bilateral tracheoesophageal grooves were negative in CT scans, and bilateral internal jugular chain and bilateral superclavicular lymph node were both negative in clinical examination. 3FD dissection, which could increase the rate of operative complication, was not conventionally used.