Objective:To explore bromodomain and extra-terminal (BET) inhibition in the regulation of vascular endothelial cells activation and early atherosclerosis formation and its potential molecular mechanisms.Methods:1.Human umbilical vein endothelial cells (HUVEC) and mouse heart endothelial cells (MHEC) were isolated,and tumor necrosis factor α (TNFα) was used to activate in flammatory genes transcription in the presence or absence of JQ1,a specific BET inhibitor.The groups are as follows:(1)Normal control group;(2) TNFα(25 ng/mL)group;(3) TNFα+JQ 1 group.The gene mRNA and protein expression of inflammatory cytokines were measured by both real-time PCR and flow cytometry (FCM).2.LDL receptor-deficient (LDLR-/-) mice were randomly divided into 2 groups:JQ1 group (n=8,JQlintraperitoneal,50 mg/kg,daily) and control group (n=8,DMSO,daily).After 8 weeks feeding with high cholesterol diet,vascular cell adhesion molecule-1 (VCAM-1) expression in aortic arch was measured by immunohistochemistry.The activity of nuclear factor kappa B (NF-κB) signaling was monitored by 5XκB luciferase reporter assay in HEK293.Results:TNFα dramatically induced the mRNA and protein expression of inflammatory genes and JQ 1 significantly downregulated the induction of them (E-selectin,P-selectin,VCAM-1,IL-8)(P＜0.01).Immunohistochemistry detection indicated that JQ1 significantly downregulated the expression of VCAM-1 in aortic arch induced by 8 weeks high cholesterol diet feeding comparing to control group.In addition,BET bromodomain inhibition downregulated TNFα upregulated NF-κB transcriptional activity (P＜0.01).Conclusions:Our study demonstrated that BET bromodomain was involved in NF-κB mediated inflammatory genes expression;inhibition of BET bromodomain suppressed vascular endothelial activation in vitro,and attenuated early atherogenesis in vivo.

Being introduced in Korean peninsula, Chinese medicine, which is called Korean medicine in Korea, has caused great influence in Korean ethnomedicine, culture and living.Korean medicine takes an important part in Korean medical education and medical treatment. This paper introduces the origin of Korean medicine, the current mode and feature of Korean medicine education, as well as the overview and characteristic of Korean Hospital Affiliated Qing Xi University and Korean Hospital Affiliated Daejeon University. The mode of Korean medical education and hospital can offer reference for Chinese medicine education.

Objective To investigate the Video?Electroencephalography(VEEG)characteristics and abnormal rate among healthy elderly. Meth?ods According to the age,120 healthy elders were divided into groups A,B,and C. Group A has 57 subjects,aged 60?69 years old;group B has 42 people,aged 70?79 years;group C has 21 individuals,aged≥80 years. Chi square and Rank sum test were used to calculate abnormal rate of VEEG. Additionally,characteristics of alpha、slow wave and Iconic sleep wave were analyzed. Result The total abnormal rate of VEEG was 42.5%, and it was particularly high(76.2%)among elderly over 80s. Frequency,amplitude,reactivity of Alpha wave and alpha index decreased as age in?creased. Theta slow wave increased as age increased,abnormal frontal area theta showed an increase among elderly over 80 s. Each sleep cycle iconic sleep wave was gradually decreased in the elderly. No statistical difference was found about sleep spindles and vertex sharp among different groups . Positive occipital sharp transients of sleep(POSTS)decreased as age increased. There was no POSTS among elderly over 80 s. Conclusion Our re?sults showed that abnormal rate is increased in the elderly,while reactivity variation,slow alpha frequency,alpha amplitude,alpha index are de?creased. In addition,the slow waves in frontal area is increased,. sleep cycles becomes less distinct,and the typical wave are decreased.

This study was aimed to investigate the effects of high-dose strictosamide injection on cardiovascular sys-tem of anesthetized beagle dogs and to examine the inhibition of strictosamide on ion channels in vitro. Indexes such as changes of systolic blood pressure (Sys), diastolic blood pressure (Dia), mean blood pressure (MBP), heart rate (HR), PR, QRS, QT, QTcb and QTcv at different time points before and after strictosamide injection in dogs were monitored by the polygraph system. The inhibition of strictosamide at different concentrations on hERG potassium channel in CHO-hERG cells and Nav1.5 sodium channel in HEK-293-Nav1.5 cells were measured by whole-cell patch-clamp method. The results showed that compared with the blank control group, Sys, Dia, MBP and HR were obviously declined 15 min after medication in the strictosamide (60, 18 mg·kg-1) group and the vehicle-control group (containing tween-80) (P < 0.05). After medication, all indexes were recovered. Compared to the vehicle-control group, there were no significant differences at different time points in each medication groups. Compared with the blank control group and before medication, the QT interval, QTcb and QTcv were significantly prolonged 15 min af-ter medication in the strictosamide (60, 18, 6 mg·kg-1) group and the vehicle-control group (P< 0.05). When medi-cation stopped, indexes were recovered at certain level. Compared with the vehicle-control group, there were no sig-nificant differences of QT interval, QTcb and QTcv of each medication group at different time points (P> 0.05). The inhibition of strictosamide on hERG potassium channel and Nav1.5 sodium channel were weak with IC50 values of 560.8 μM and > 900 μM, respectively, which were far greater than the positive controls. It was concluded that sin-gle, high-dose intravenous injection of strictosamide may lead to a lower blood pressure, a slower heart rate and a prolongation on the QT interval in beagle dogs, which returned to basal levels when medication stopped. It was spec-ulated that the reduction of blood pressure and the slowing of heart rate were related to tween-80 contained in the vehicle control group. No significant inhibitory effects were detected on hERG potassium channel and Nav1.5 sodium channel in vitro, which suggested that other mechanisms may be involved in strictosamide-induced QT interval pro-longation in animals.

Objective To investigate the effect of soluble Tie2 fusion protein(sTie2/Fc)on the angiogenesis of peritoneal vessels in uremic peritoneal dialysis (PD) rats.Methods Rats were randomly divided into 6 groups:normal rats as control group (group1),rats with sham operation (group2),uremic rats without PD (group3),uremic rats dialyzed with 4:25％ PD solution (group4),uremic rats dialyzed with 4.25％ PD solution and treated by subcutaneous injection of 2.5 μg/kg sTie2/Fc (group5),uremic rats dialyzed with 4.25％ PD solution and treated by subcutaneous injection of 5.0 μg/kg sTie2/Fc (group6).sTie2/Fc was given every other day during peritoneal dialysis period,total 14 doses.After regular PD for 28 days,RT-PCR and tissue immunohistochemical staining were used to detect the mRNA and protein expressions of Angpt-2 in peritoneal tissues in each group of rats.Microvessel density (MVD) of peritoneum was detected and quantified with immunohistochemical staining by using anti-CD34 antibody.Results The expression of Angpt-2 mRNA and protein was found in each group.There was no significant difference of.Angpt-2 expression both in mRNA and protein level between group1 and group2.Compared with group1,the mRNA and protein expression of Angpt-2 were significantly increased in group3 and group4 (all P＜0.05).Compared with group3,the mRNA and protein expression of Angpt-2 were significantly increased in group4 (all P＜0.05).Compared with group 4,the mRNA and protein expression of Angpt-2 were significantly decreased in group5 and group6 (all P＜0.05).Compared with group5,the mRNA and protein expression of Angpt-2 were significantly decreased in group6 (all P＜0.05).Only few new microvessel was found in group1 and group2.Compared with group1,MVD was significantly up-regulated in group3 and group4 (all P＜0.05).Compared with group4,MVD was significantly down-regulated in group5 and group6 (all P＜0.05).Conclusions Peritoneum neoangiogensis can be effectively inhibited by sTie2/Fc in uremic rat treated with PD.Blocking of signal transduction may be involved in the mechanism of sTie2/Fc inhibiting peritoneal angiogenesis.

To detect cadmium ions, we constructed a specific microbial sensor and screened detecting cassettes and different fluorescence proteins. Blue fluorescence protein mTagBFP2 was selected as a reporter and a double-promoters model was used in the construction of the fusion reporter vector Pmer::merR-m-Pmer::mTagBFP2-pMD19-T. The reporter vector was then transformed into Escherichia coli MC4100 wild type strain. The medium, incubation time, initial density for induction, and the optimal detection range were determined. The specificity of the biosensor was also checked. The biosensor responded specifically to cadmium irons with low background, and the linear concentration range detection ranged from 0.1 to 75 μmol/L at the initial OD600 = 0.1 with 2 h incubation in IHMM medium. Thus we successfully constructed a specific biosensor to detect cadmium irons and provided useful strategies for development and optimization of microbial sensors to detect heavy metals.
Biosensing Techniques ; Cadmium ; analysis ; Escherichia coli ; Genetic Vectors ; Promoter Regions, Genetic

This study aimed at investigating the antiviral constituents from the active fractions of Tong-An (TA) injection.In this study,the active constituents of TA injection were screened by LPS-induced PGE2 production mode to detect the contents of PGE2.The chemical constituents were isolated by HP-20 macroporous resin,silica gel column chromatography,ODS column chromatography,Sephadex LH-20 column chromatography and preparative and semi-preparative HPLC.The structures were identified by spectral data and physicochemical property.As a result,the 95％ ethanol eluate of TA injection on the macroporous adsorption resin column was proved to be the active fraction of TA injection.Seventeen compounds were isolated from TA injection and identified as syringaresinol (1),N-Trans-Feruloyltyramine (2),chelerythrine (3),sinomenine (4),coptisine (5),sanguinarine (6),chelidoniny (7),magnoflorine (8),allocryptopine (9),protopine (10),farrerol (11),dihydrosanguinarine (12),heptadec-(9Z)-enoic acid (13),chlorogenic acid (14),cryptochlorogenin acid (15),3,5-di-O-caffeoylquinic acid (16) and 4,5-di-O-caffeoylquinic acid (17).PGE2 inhibitory activities of these compounds were determined,among which six compounds presented inhibitory activities against PGE2.It was concluded that all the isolated compounds from TA injection were firstly reported with the favorable inhibitory activities of compounds 2,5,9,10,11,12 against PGE2.

ObjectiveTo investigate the expression of TM6SF2 in hepatocellular carcinoma (HCC) tissue and its biological functions by data mining in tumor databases. MethodsThe GEPIA database was applied to measure the change in the mRNA expression level of TM6SF2 in HCC tissue, and OncoLnc was used to analyze the association of TM6SF2 expression with the survival time of HCC patients. The cBioPortal and LinkedOmics databases were used to analyze the genes associated with the expression of TM6SF2 in HCC tissue, and the DAVID6.8 and STRING databases were used to perform a bioinformatics analysis of TM6SF2 and the genes associated with its expression. The t-test was used to investigate the difference in the mRNA expression of TM6SF2 between HCC tissue and adjacent tissue. The Spearman correlation coefficient was used to analyze the correlation of gene expression. The Kaplan-Meier method was used to calculate survival percentage, and the log-rank test was used to analyze the difference in survival percentage. ResultsCompared with the normal liver tissue, the HCC tissue had low mRNA expression of TM6SF2 (｜log2FC｜cut-off = 0.5, P＜0.01). Compared with those with high expression of TM6SF2, the patients with low expression had a significant reduction in overall survival time (χ2=9.897，P＜0.01). Data analysis showed that a total of 49 genes were associated with the expression of TM6SF2 in HCC tissue, and the gene ontology analysis showed that these genes were enriched in the biological processes and functions including fatty acid synthesis, fatty acid ligase activation, and thrombin regulation (P＜0.05). The Kyoto Encyclopedia of Genes and Genome pathway analysis showed that these genes were mainly involved in the signaling pathways of alanine metabolism, peroxisome proliferator-activated receptor signaling pathway, and bile secretion (P＜0.05). The protein-protein interaction network analysis showed that the genes of SERPINC1, NR1I2, SERPINA10, and SLC10A1 had marked or potential interaction with TM6SF2 (P＜0.01). ConclusionTumor data mining can quickly obtain the information on the expression of TM6SF2 in HCC tissue and provide a bioinformatics basis for exploring the role of TM6SF2 in the development and progression of HCC.

Objective To evaluate the multimodal treatment outcomes and patterns of treatment failure in esthesioneuroblastoma at a single institution. Methods One hundred and twelve patients who were newly diagnosed with esthesioneuroblastoma but no distant metastasis in our institution from 1979 to 2014 were retrospectively analyzed. The treatment modes, outcomes, and patterns of treatment failure in these patients were analyzed. According to the modified Kadish staging system, the numbers of patients with stage A, B, C, and D esthesioneuroblastoma were 1, 23, 60, and 28, respectively. Fifty?one patients received surgery and postoperative radiotherapy with or without chemotherapy;forty?six patients received radiotherapy with or without chemotherapy;eleven patients received preoperative radiotherapy and surgery with or without chemotherapy;three patients received surgery with or without chemotherapy; one patient received chemotherapy alone. The survival rates were calculated using the Kaplan?Meier method. Results In all patients, the 5?year sample size was 44, and the 5?year overall survival ( OS ) and disease?free survival ( DFS) rates were 66?4% and 54?7%, respectively. The 5?year OS and DFS rates were 91% and 82% in patients who received preoperative radiotherapy and surgery with or without chemotherapy, 80% and 66% in patients who received surgery and postoperative radiotherapy with or without chemotherapy, and 46% and 37% in patients who received radiotherapy with or without chemotherapy. Three patients treated with surgery alone had relapse of the disease;one patient treated with palliative chemotherapy survived 6 months. Treatment failed in 47 ( 42%) out of 112 patients. In patients with failed treatment, 53% had distant metastasis as the first pattern of treatment failure, 36% had locoregional relapse, and 11% had concurrent distant metastasis and locoregional relapse. Conclusions Surgery combined with radiotherapy is still the recommended multimodal treatment regimen for esthesioneuroblastoma. The multimodal treatment achieves satisfactory local?regional control rate and treatment outcomes in the treatment of esthesioneuroblastoma. The major pattern of treatment failure is distant metastasis.

Summarize the application of SOAP in the medical field and find out its problems in the course of traditional Chinese medicine, to explore the significance and value of SOAP in teaching practice in TCM. Organize relevant literature and discuss the application of SOAP in the course of Chinese medicine. SOAP is widely used in various aspects of medicine, and there are still some problems in the course of TCM. The use of SOAP model for teaching and assessment has important practical significance and value in the course of Chinese medicine internal medicine practice, and SOAP emphasize the practice of the post competence oriented teaching, which is worth promoting.