Objective To investigate the clinical value of human soluble endothelial protein C receptor (sEPCR) after heart valve replacement.Methods 78 cases of patients with heart valve replacement in the Second Affiliated Hospital of Nantong University from January 2005 to June 2016 were selected as the research objects,who were divided into embolic group and control group,38 cases in embolic group and 40 cases in control group,the index of two groups 1 d preoperative,while dynamic monitoring international standardization ratio (INR) and embolism,were detected,of which INR and sEPCR were examined.The INR and sEPCR oftwo groups was compared with t test.Results The INR and sEPCR of two groups 1 d preoperative had no significant difference (1.24±0.32 vs 1.23±0.19,34.91±9.14 μg/L vs 35.56±10.22 μg/L;t=0.17,P =0.868;t=0.30,P=0.768,respectively).The average value of dynamic monitoring INR in control group had no significant difference when compared with the results of embolism (1.86±0.95 vs 1.93±0.97,t=0.32,P=0.748).But the sEPCR had significant difference (101.33±27.15 μg/L vs 41.67±11.82 μg/L,t=12.69,P=0.000).Conclusion The important indexes of sEPCR could effectively guide the anticoagulant treatment,especially those who with the sEPCR value too high,the embolic threatening should be paid attention to.

Objective To analyze the distribution of common chromosomal karyotypes of patients with Turner syndrome (TS), and to explore the correlation between the age and height standard deviation scores (HSDS) on diagnosis.Methods Retrospective investigation was performed for the data of age and HSDS on diagnosis in 273 TS girls(≤ 18.0 years old)diagnosed by chromosomal karyotypes.The main statistical methods were analyzed with t-test and Pearson correlation test by using the SPSS 18.0 statistical software.Results (1) There were 4 kinds of common chromosomal karyotypes in the TS :45, X (87/273 cases,31.9％),46, X, i (Xq) (43/273 cases, 15.7％) ,45, X/46, X, i (Xq) (36/273 cases, 13.2％) and 45, X/46, XX (23/273 cases, 8.4％), respectively, the adolescent TS all had delayed puberty.For the cases with 45, X karyotypes ,3 cases presented mental retardation and 2 cases with organs deformity.(2)The patients with 45 ,X/46,X,i(Xq) karyotypes or with 46,X,i(Xq) karyotypes had the maximum(12.56 age) or the minimum(9.70 age) mean age on diagnosis, respectively, there was a significant difference between 2 groups (t =3.019, P =0.004).The maximum deviation from normal height was found in the patients with karyotypes of 46, X,i (Xq) (HSDS =-4.04), and the minimum deviation was in the patients with karyotypes of 45,X/46, XX (HSDS =-3.16), and there was a significant difference between 2 groups (t =-2.95, P =0.004).(3) More than 75.7％ of TS patients was diagnosed when their heights deviated above 3 SD,and their mean age on diagnosis was 12.10 age,which was 3 years later than those patients within 2 SD.(4) There was a significant negative correlation between the age and HSDS on diagnosis in the groups of common chromosomal karyotypes[45,X、46,X,i(Xq) and 45,X/46,XX] (r =-0.551,-0.560,-0.622,all P ＜ 0.01), except for the group with the 45, X/46, X, i (Xq).Conclusions (1) In this study, the consti-tuent ratios of these 4 common chromosomal karyotypes were different from those in Europe and America's.(2)Patients with 45 ,X may have more severe symptoms than others.(3)The mean age on diagnosis was at least 3.0 years earlier when considered HSDS below-2.00 as an indicator for chromosomal karyotype screening,which would facilitate earlier diagnosis.

Objective To perform mutation analysis of survival motor neuron gene 1 (SMN1 in two spinal muscular atrophy (SMA) patients and their parents to evaluate the effects of the two SMN1 gene mutations on the transcript levels of the gene and preliminarily predict their effects on the structure and function of SMN protein.Methods Mutation analysis of SMN1 gene was carried out by multiplex ligationdependent probe amplification,reverse transcript-polymerase chain reaction (RT-PCR) and cloning sequencing.Transmission of the mutations was confirmed by the mutation analysis in patients' parents.The full-length SMN1 (SMN1-fl) transcript levels of the patients carrying these subtle mutations were detected using quantitative RT-PCR.Results The two patients were diagnosed as SMA Ⅱ and SMA Ⅲ.They carried p.Val19GlyfsX21 and p.Ala2Gly SMN1 mutations in SMN1 gene,respectively.Both of the two mutations were originated from their fathers.Compared with the healthy individuals (23.5 ± 4.9),the two patients had a significant reduction in the level of SMN1-fl transcripts (t =3.322,P =0.011 (p.Ala2Gly) ;t =6.964,P =0.000 (p.Val19GlyfsX21)).However,compared with the healthy carriers (14.1 ±4.5),the patient with p.Ala2Gly mutation had no significant reduction in the level of SMN1-fl transcripts (13.9 ±3.6,t =0.058,P =0.955) ; however,the patient with p.Val19GlyfsX21 mutation had a significant reduction (4.9± 2.4,t =3.725,P =0.004).Conclusions Two SMN1 gene mutations are identified in our study.The mutation p.Val19GlyfsX21 is a novel mutation and p.Ala2Gly is firstly reported in Chinese SMA patients.p.Val19GlyfsX21 may possibly lead to decreased SMN1-fl mRNA by nonsense-mediated messenger RNA decay,however,p.Ala2Gly has no obvious effects on the amount of the SMN1-fl transcripts,indicating that its deleterious effect may be occurring at SMN protein level or the function of SMN protein.

Objectives: Currently, more than 80% of Korean police officers are assigned to a 24-hour rotating shift system. Shift workers’ sleep patterns change frequently, which may result in circadian rhythm desynchrony and sleep disturbance. The goal of this study was to compare sleep and cognitive functioning in different shift types. In addition, we analyzed the difference in cognitive functioning depending on whether shift workers took a night nap prior to their night shift. Methods: A total of 278 police officers working in Seoul (mean age 45.27±9.00 years, 88.5% male) participated, providing demographic information and completing selfreport questionnaires [Insomnia Severity Index, Epworth Sleepiness Scale, Munich ChronoType Questionnaire (Shift-work type), Patient Health Questionnaire-9]. Participants also performed the Psychomotor Vigilance Task, Trail Making Test A & B, and Stroop Test. Results: Participants included 57 (20.5%) day workers and 221 (79.5%) shift workers. The average Insomnia Severity Index score of shift workers was significantly higher than day workers (t=-2.861, p=0.005). Shift workers also slept about 0.78 hours less than day workers (t=4.730, p<0.001). Among shift workers, 66.3% (n=128) reported they took night naps prior to their night shift, sleeping on average 1.78 hours. Shift workers who took night naps had faster reaction times on the Trail Making Test A task [F(1, 136)=5.741, p=0.018], and significantly fewer Stroop C errors [F(1, 137)=5.638, p=0.019] than those who did not. Conclusions Shift working police officers reported significantly worse insomnia symptoms and slept less compared to their non-shift-working counterparts. Taking a night nap improved focused and selective attention.

Objectives: Currently, more than 80% of Korean police officers are assigned to a 24-hour rotating shift system. Shift workers’ sleep patterns change frequently, which may result in circadian rhythm desynchrony and sleep disturbance. The goal of this study was to compare sleep and cognitive functioning in different shift types. In addition, we analyzed the difference in cognitive functioning depending on whether shift workers took a night nap prior to their night shift. Methods: A total of 278 police officers working in Seoul (mean age 45.27±9.00 years, 88.5% male) participated, providing demographic information and completing selfreport questionnaires [Insomnia Severity Index, Epworth Sleepiness Scale, Munich ChronoType Questionnaire (Shift-work type), Patient Health Questionnaire-9]. Participants also performed the Psychomotor Vigilance Task, Trail Making Test A & B, and Stroop Test. Results: Participants included 57 (20.5%) day workers and 221 (79.5%) shift workers. The average Insomnia Severity Index score of shift workers was significantly higher than day workers (t=-2.861, p=0.005). Shift workers also slept about 0.78 hours less than day workers (t=4.730, p<0.001). Among shift workers, 66.3% (n=128) reported they took night naps prior to their night shift, sleeping on average 1.78 hours. Shift workers who took night naps had faster reaction times on the Trail Making Test A task [F(1, 136)=5.741, p=0.018], and significantly fewer Stroop C errors [F(1, 137)=5.638, p=0.019] than those who did not. Conclusions Shift working police officers reported significantly worse insomnia symptoms and slept less compared to their non-shift-working counterparts. Taking a night nap improved focused and selective attention.

OBJECTIVES: Treatment response of bipolar disorders (BDs) to long-term mood stabilizers maintenance has not been well explored because of complicated clinical and treatment courses. This study aims at investigating long-term clinical response of BDs to lithium and/or valproate in a naturalistic setting of a tertiary-care university-affiliated hospital. METHODS: Subjects were 65 patients with bipolar I (BD-I) disorders who had been treated with lithium and/or valproate for more than two years at single bipolar disorder clinic. Long-term response to the best treatment based on treatment algorithms and the current clinical standard of care was retrospectively evaluated using the Alda Scale and the Clinical Global Impression Scale for use in bipolar illness (CGI-BP). Patients were classified into full responder and partial/non responder groups based on the total score of the Alda Scale with the cut-off score generated from the frequentist mixture analysis of the authors' previous study. RESULTS: The mean duration of treatment with the index medication was 69.2 months. Baseline demographic and clinical characteristics were not different among three mood stabilizer groups (valproate, lithium, and combination groups). Twenty-one subjects were classified into full responder group (32.3%). Treatment response assessed by the Alda Scale and CGI-BP scores was not different between lithium and valproate groups. The Alda Scale scores were well correlated with the CGI-BP scores (p < 0.05). CONCLUSIONS: One third of the patients showed a full response to the long-term lithium and/or valproate treatment in BD-I. The degree of response was similar between lithium and valproate groups.
Bipolar Disorder ; Humans ; Lithium* ; Retrospective Studies* ; Standard of Care ; Valproic Acid*

OBJECTIVETo understand the pathogenic effect and the correlation between the genotype and phenotype of the 4 novel missense mutations (G247S, E280G, P362T and A434D) of phenylalanine hydroxylase gene (PAH).

METHODS(1) The enzyme activity of the 4 mutants was assessed by using transient protein expression in mammalian cells. (2) The PAH amino acid sequences among different animal species were alignmented. (3) The effects of the 4 missense mutations on the protein structure were analyzed. (4) The clinical phenotype of the patients with PKU were analyzed, according to their blood Phe levels prior to treatment and the Phe tolerance.

RESULTS(1) The residual enzyme activity expressed in vitro of G247S, E280G, P362T and A434D were 3.1%, 0.4%, 8.2% and 21.7% of the wild-type PAH respectively; (2)Gly247, Glu280 and Pro362 were among the highly conserved amino acids, while Ala434 was only moderately conserved; (3) As revealed by 3D structural analysis, G247S and E280G, being located at the active center of the enzyme, interfered with the binding of PAH to BH4 and ferrousion respectively, while P362T and A434D affected the formation and stability of the dimer and the tetramer of PAH; (4) As shown by clinical phenotypic analysis, classical PKU were observed in patients carrying G247S and E280G, moderate PKU were observed in patients carrying A434D, whereas both classical and moderate PKU were observed in patients carrying P362T.

CONCLUSION(1) The E280G, G247S, P362T and A434D are all disease-causing mutations, with those located at the center of the enzyme displaying the most marked pathogenic effect; (2)The results of the structural analysis of the 3D molecule are consistent with the activity assessment of the enzyme expressed in vitro; (3) The consistency is observed between the genotype, the enzymatic activity expressed in vitro and the clinical phenotype.

Amino Acid Sequence ; Animals ; Child ; Child, Preschool ; Female ; Gene Expression ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins ; chemistry ; genetics ; metabolism ; Mutation, Missense ; Phenotype ; Phenylalanine Hydroxylase ; chemistry ; genetics ; metabolism ; Phenylketonurias ; enzymology ; genetics ; Protein Conformation ; Sequence Alignment ; Structure-Activity Relationship

OBJECTIVETo establish a hyperphenylalaninemia related genes screening method using Ion Torrent Personal Genome Machine (PGM) for early detection and differential diagnosis of hyperphenylalaninemia (HPA).

METHODSThree children with known HPA mutations and a healthy control were used for setting up the method. Ten children with HPA with known mutations were recruited for validating the method. Ion Ampliseq PCR was used to amplify the 5' and 3' untranslated region, coding sequence, and flanking introns of PAH, GCH1, PTS, QDPR, and PCBD1 genes. After the enrichment with the Ion OneTouch system, the products were sequenced by PGM. Data from the PGM were processed with Torrent Suite v2.2 software package. All variations were confirmed by Sanger sequencing.

RESULTSFor the 4 samples, the PGM output was 94.22 Mb, with approximately 99.5% of reads mapping to the target regions. Among these samples, we detected 74 variations (28 positions) including 6 known mutations. Compared with database and results of Sanger sequencing, 55 (18 positions) polymorphisms and 13 (4 positions) false positive calls were confirmed. For the 10 samples, all the known mutations were successfully identified.

CONCLUSIONIon Torrent PGM sequencing is suitable for screening genetic mutation underlying HPA from the perspective of metabolic pathways, which can meet the clinical demand for individualized diagnosis and treatment.

High-Throughput Nucleotide Sequencing ; methods ; Humans ; Mutation ; Phenylketonurias ; genetics

BACKGROUND: Angiotensin II (AngII) and abnormal oscillatory shear stress are highly associated with vascular inflammation including atherosclerosis. However, it is poorly understood how interactions between AngII and shear stress in human aortic endothelial cells (HAEC) are involved in mechanisms by which cellular adhesion molecules are expressed. The purpose of this study was to improve that understanding. METHODS: AngII (10(-7)M for 6 hr) and two-types of shear stress treatments were used: laminar shear stress (LS: unidirectional, 12 dynes/cm2) and oscillatory shear stress (OS: bi-directional, 5 dynes/cm2, 1 Hz) in HAEC. Immunoblotting was used to detect expression of cellular adhesion molecules markers such as vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1). RESULTS: AngII significantly increased VCAM1 and ICAM1 expression in HAEC that had been reduced due to pretreatment with telmisartan. AngII-LS co-stimulation and AngII-OS co-stimulation significantly increased VCAM1 and ICAM1 expression in HAEC. The expression levels of VCAM1 and ICAM1 were also, significantly reduced when pretreated with telmisartan. However, VCAM1 and ICAM1 expression were significantly reduced under LS and OS stimulation. CONCLUSIONS: Telmisartan may modulate the expressions of VCAM1 and ICAM1 via different types of shear stress in HAEC that are activated by AngII.
Angiotensin II ; Angiotensins ; Atherosclerosis ; Benzimidazoles ; Benzoates ; Endothelial Cells ; Humans ; Immunoblotting ; Inflammation ; Intercellular Adhesion Molecule-1 ; Vascular Cell Adhesion Molecule-1

BACKGROUND: Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. METHODS: Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. RESULTS: We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old). CONCLUSIONS: Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.
Astrocytoma ; Classification ; Diagnosis ; Disease-Free Survival ; Genetics ; Glioblastoma ; Glioma ; Humans ; Necrosis ; Oligodendroglioma ; Pathology ; Prognosis ; Seoul