Objective To investigate the feasibility, accuracy and senaitivety of echo tracking (ET) technology on carotid elasticity in rabbits. Methods Thirty-nine healthy New Zealand rabbits were divided into 4 groups,which group 1,2,3 were experimental groups and group 4 was control group. Experimental groups were fed with high cholesterol diet,control group were fed with basic diet. The parameters of elasticity of carotid were measured with ET technology, including pressure-strain elasticity modulus(Ep), stiffness parameter(β), arterial complianee(AC), pulse wave velocity( PWV), augmentation index (AI) at the interval of 0,4,8,12 weeks of the experiment respectively. Blood-fat level of all rabbits were checked and the common carotid artery was examined pathologically,which were compared and analyzed then. Results With the prolong of the experiment time,the Ep and β raised, but the AC reduced. There were significant difference between experimental group 1 (4 weeks) and basement,which were same between experimental group 2 (8 weeks) and experimental group 1, between experimental group 3(12 weeks) and experimental group 2( P<0.05). PWV increased comparing with basement in the end of 8 weeks,which increased obviously in the end of 12 weeks,meanwhile was higher than in the end of 8 weeks,which there were significant differences ( P<0.01 ). AI had no change all the time. Conclusions ET technology is accurate and reliable in detecting early atherosclerosis. Probe maintenance tool can keep the steady of checking progress, sensitive of result and repeatability.

Humans ; Malocclusion, Angle Class I ; therapy ; Orthodontic Appliance Design

Objective To evaluated the effect of the regional cooperative rescue model implemented on the length of time from first medical contact (FMC) to balloon dilation (B),economic expense and prognosis in patients with acute coronary syndrome (ACS).Methods Patients with ACS (including ST-segment elevation and non-ST-segment elevation) selected from other hospitals within 24 hours after onset were treated with emergency percutaneous coronary intervention.Patients were divided into two groups, regional cooperative rescue group and control group without the regional cooperative rescue model approved.The lengths of FMC-to-B time and Door-to-B time (from arrival at emergency department or OPD to balloon dilation),time required for patients referred to our hospital,cardiac function,averaged hospital costs,average hospital stay,percentage of medication used and a major adverse cardiac event (MACE) were analyzed.Results Mean FMC-to-B time,Door-to-B time,referral time and time consumed to obtain informed consent were significantly shorter [(106±33) min,(31 ±8) min,(62 ±18,8 ±3) min] vs.[(231 ±35) min,(109 ±26) min,(98 ±31) min,(28 ±11) min,respectively] by implementing the regional cooperative rescue compared with control group,and LVEF was increased,and LVED was deceased inregional cooperative rescue group.The mean costs [(44 123.0 ±3 427.0) yuan vs.(51 587.0 ±5 621.0)] yuan,days of hospital stay [(8.7 ±4.1) vs.(13.2 ±6.4)] and percentage of medication used were significantly decreased in the regional cooperative rescue group.The incidence of MACE inregional cooperative rescue group was 6.2％,whereas the incidence in control group was 16.8％.Conclusions The regional cooperative rescue model can improve the prognosis and decrease the FMC-to-B time,the rate of MACE and financial burden in patients with ACS.

Cytophagocytosis ; Humans ; Plaque, Atherosclerotic ; physiopathology

Aim To investigate whether necroptosis mediates chemical hypoxia-induced HT22 mouse hippocampal cell injury and inflammation.Methods HT22 hippocampal cells were exposed to cobalt chloride (CoCl2) to establish a model of the chemical hypoxia-induced injury and inflammation.The expression level of RIP3 (an index of necroptosis) was determined by Western blot.Cell counter kit-8 (CCK-8) assay was used to test the cell viability.Lactate dehydrogenase (LDH) activity in the culture medium was measured with commercial kits.Mitochondrial membrane potential (MMP) was examined by rhodamine123 staining followed by photofluorography.The intracellular level of reactive oxygen species (ROS) was detected by 2', 7'-dichlorfluorescein-diacetate (DCFH-DA) staining followed by photofluorography.The secretion levels of interleukin-1β (IL-1β) and tumor necrosis factor-a (TNF-α) were measured by ELISA.Results Treatment of HT22 hippocampal cells with 600 μmol·L-1 CoCl2 for 36 h markedly induced cytotoxicity, leading to a decrease in cell viability to (52.0±2.65) % , indicating that chemical hypoxia-induced cellular injury model was successfully set up.Besides, CoCl2 induced considerable injuries and inflammation, evidenced by increases in LDH activity, ROS production, MMP loss, as well as the secretion levels of IL-1β and TNF-α.Co-treatment of the cells with 40~100 μmol·L-1 Nec-1 (a specific inhibitor of necroptosis) and CoCl2 markedly attenuated the decrease in viability induced by CoCl2, reaching the best anti-cytotoxicity inhibitory effect at 80 μmol·L-1.Meanwhile, the co-treatment with 80 μmol·L-1 Nec-1 blocked the above injuries and inflammatory response induced by CoCl2.In addition, treatment of HT22 hippocampal cells for 6~48 h up-regulated the expression of RIP3, and Nec-1 alleviated the up-regulation of RIP3 expression level induced by CoCl2.Conclusion Necroptosis mediates chemical hypoxia-induced HT22 hippocampal cell injury and inflammation.

Human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) is a long-term cardiovascular complication of AIDS patients, with an incidence of about 0.5%. The onset of HIV-PAH is insidious and lack of specific symptoms with poor prognosis. The pathogenesis is complicated while the bystander effect of HIV or the complication of HIV is possible mechanism. Echocardiography is an important diagnostic method and facilitates early screening of patients. At present, there is no specific drug targeted HIV-PAH, and the treatment strategy is to follow the treatment recommendations for idiopathic pulmonary arterial hypertension on the basis of highly active antiretroviral therapy, while the interaction between two types of drugs should be considered. This paper will mainly focus on the pathogenesis and treatment of HIV-PAH.

Objective To investigate if miR-145a-5p participates the modulation process of CD137 signaling on the expression of nuclear factor of activated T cells c1 (NFATc1) in ApoE-/-mice.Methods Atherosclerotic plaque model was produced by perivascular carotid collar placement in ApoE-/-mice.After surgery, the mice were randomly divided into the following groups: CD137 activated group (CD137 group, n =6) ,CD137 inhibited group (anti-CD137 group, n =6) and control group(n =6).The mRNA expression of miR-145a-Sp in plaque and cells was measured by real-time quantitative PCR (RT-PCR).Immunofluorescence was used to observe the distribution of NFATc1 in plaque and the expression of NFATc1 at mRNA and protein levels were detected by qRT-PCR, Western blot, respectively.The mouse vascular smooth muscle cells (VSMCs) were isolated and transfected with miR-145a-5p mimics or inhibitors by Lipofectamine.The eukaryotic expression vector and luciferase vector including p3xFLAG-NFATc1, p3xFLAG-NFATc1-3'UTR,psicheck2-NFATc1, psicheck2-NFATc1-Mut were constructed through molecular cloning and homologous recombination techniques, 293T cells were transfected with the miR-145a-5p mimics or inhibitors and the protein level and fluorescence intensity were then measured, respectively.Results In vivo or in vitro, the level of miR-145a-5p was significantly decreased (0.21 ± 0.06 vs.1.00 ± 0.00, P ＜0.05,0.22 ± 0.07 vs.0.50 ± 0.12, P ＜ 0.05) while the opposite effects were observed in anti-CD137 group.NFATc1 expression was decreased or increased in VSMCs transfected with miR-145a-5p mimics or inhibitors, respectively (all P ＜ 0.05).miR-145a-5p mimics decreased the expression of p3xFLAG-NFATc1-3'UTR and the fluorescence intensity (0.56 ± 0.08 vs.1.00 ± 0.00, P ＜ 0.05).Conclusion CD137 signaling participates the regulation process on the expression of NFATc1 through miR-145a-5p in ApoE-/-mice.

Objective To investigate the association between CD 147 expression and its untranslated regions 3′UTR rs8259 T/A polymorphism and acute coronary syndrome ( ACS).Methods The genotypes of CD147 were detected by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) methods in 182 ACS patients and 328 healthy controls.The plasma level of CD147 was determined by enzyme-linked immunosorbent assay (ELISA).CD147 mRNA and protein expression was detected by real-time fluorescent quantitative PCR ( RT-qPCR ) and Western blot.Results The plasma CD147 level obtained from radial artery in ACS patients ((3.63 ±0.70) pg/L) was significantly higher than in control ((2.45 ±0.27) pg/L, P<0.05), and highest in plasma obtained from the coronary artery ((4.28 ± 1.03)pg/L, P<0.05) in ACS patients.Furthermore, the plasma CD147 level was higher in the ACS patients with rs8259 AA genotype than in the ACS patients with rs 8259 TT genotype ((4.08 ±0.41) pg/L vs.(3.05 ±0.79) pg/L in radial artery and (5.29 ±0.62) pg/L vs.(3.13 ±0.52) pg/L in coronary artery, both P <0.05 ).There are an enhanced expression of CD 147 mRNA ( 2.45 times higher than control) and protein (3.66 ±1.56 vs.1.81 ±1.29) in PBMCs from ACS patients than that from controls (both P<0.05).The PBMCs CD147 mRNA and protein expression level were significantly higher in ACS patients with rs8259 AA genotype (mRNA:2.45 ±0.35, protein:1.63 ±0.16) compared to ACS patients with rs8259 TT genotype ( mRNA:1.69 ±0.15, protein:0.88 ±0.16, both P<0.05).Multiple logistic analysis showed that CD147 T allele ( AT +TT) was a protective factor to ACS ( OR =0.667, 95%CI 0.507-0.879, P<0.05).Conclusions The over-expression of CD147 is involved in the pathogenesis of ACS.The CD147 3′UTR rs8259 T allele may be a protective factor for ACS , its polymorphism can affect the CD147 protein expression in ACS patients.

Objective The aim of this study was to determine whether inhibition of cyclophilin A by lentivirus-mediated RNA interference ( RNAi ) could inhibit progression of atherosclerotic plaques and increase collagen production .Methods Atherosclerostic plaque model was induced by rapid perivascular carotid silicone collar placement in ApoE -/-mice.The recombinant CyPA-RNAi-Lentivirus ( CyPA-RNAi-LV) or negative control-green fluorescent protein-Lentivirus ( NC-GFP-LV) were constructed and transfected into right carotid plaques , respectively.Using the local injection method , ApoE-/- mice carotid artery plaque were intervened 10 min in the silicone collar placement with 10 μl ( 1.0 ×108 TU/ml ) lentivirus vector.The areas and CyPA expression of plaques were analyzed by morphological observation , real-time polymerase chain reaction ( RT-PCR ) and Western blot respectively .Results CyPA-RNAi-LV not only prevented plaques progression ((9 085 ±671) μm2 to (18 021 ±1 901) μm2), but also decreased plaque lipid content ((28.9 ±6.3)%to (17.8 ±4.5)%), increased plaque collagen content ((24.2 ±4.8)%to (35.1 ±5.2)%) at 6 weeks after lentivirus transfection.The intima/media ratio (0.36 ±0.11 vs.0.65 ±0.12, P<0.05) and degree of lumen stenosis (intima/lumen ratios, 0.18 ±0.02 vs.0.33 ±0.03, P<0.05 ) were also significantly reduced by CyPA-RNAi-LV.Moreover , RT-PCR analysis revealed downregulated expressions of proinflammatory cytokines and matrix metalloproteinases ( MMP-9 -17.5%) in the CyPA-RNAi-LV group.Conclusion Lentivirus-mediated CyPA silencing by siRNA could inhibit plaques progression and reduce local inflammation through the anti-inflammatory effects in this model .

Objective To investigate the effect and related mechanism of CD137 stimulation on aortic atherosclerotic plaque calcification in high fat diet fed ApoE-/-mice and on calcification of vascular smooth muscle cells (VSMCs).Methods (1) ApoE-/-mice fed with high fat diet were randomly divided into 3 groups:CD137 activated group (treated by 200 μg CD137 agonist i.p.once per week for 6 weeks,n =5);CD137 inhibited group (anti-CD137 group:200 μg anti-CD137 antibody + 200 μg CD137 agonist,i.p.,once per week for 6 weeks,n =5) and control group (n =5).Von kossa staining was used to observe the calcification of the aortic plaque and VSMCs.Immunohistochemistry was used to observe the expression of BMP-2 and Runx2 which are known mediators of osteogenic differentiation.(2) The mouse aortic VSMCs were obtained by Patch-attaching method.The calcium content was measured by Methylthymol Blue complexone method.The mRNA expressions of bone morphogenetic protein 2 (BMP-2) and Runx2 were measured by real-time fluorescent quantitative PCR (RT-PCR).The protein levels of BMP-2,Runx2 of the VSMCs were determined by Western blot.Results (1) In vivo,the plaque calcified area in ApoE-/-mice was significantly larger in CD137-agonist group than that in control group ((1.75 ± 0.33) × 104 μm2 vs.(0.23 ±0.07) × 104 μm2,P ＜0.01),and this effect was significantly reduced by cotreatment with CD137-antagonist ((0.83 ± 0.30) × 104 μm2 vs.(1.75 ± 0.33) × 104 μm2,P ＜ 0.05).The levels of BMP-2 and Runx2 were all significantly upregulated in CD137-agonist group than in control group (both P ＜ 0.01),again,this effect was blocked by cotreatment with CD137-antagonist (P ＜0.05).(2) Consistent with the in vivo results,VSMCs calcification was also more serious in CD137-agonist group than in control group,which could be significantly attenuated by eotreatment with CD137-antagonist.In VSMCs,calcium content level in CD137-agonist group was higher than in control group ((0.001 3 ± 0.000 2) mmol/mg protein vs.(0.000 7 ±0.000 1) mmol/mg protein,P ＜ 0.01),which could be significantly reduced by co-treatment with CD137-antagonist ((0.000 9 ± 0.000 2) mmol/mg protein vs.(0.001 3 ± 0.000 2) mmoL/mg protein,P ＜0.01).The mRNA and protein levels of BMP-2 and Runx2 were significantly upregulated in CD137-agonist group compared with the control group (P ＜ 0.05),which could be significantly down-regulated by cotreatment with CD-137 antagonist (P ＜ 0.05).Conclusion CD137 activation can promote vascular calcification in high fat diet fed ApoE-/-mice both in vivo and in vitro.