Abstract:Aim To study the relationship between vascular cognitive impairment (VCI) degree and serum inflammatory factors in patients with cognitive dysfunction of hypertensive cerebral small vessel disease (CSVD). Methods The clinical data of 141 patients with hypertension CSVD who were treated in Affiliated Hospital of Chengde Medical College from January 2016 to October 2018 were retrospectively analyzed. Patients were divided into non-VCI (WVCI) group (n＝45), vascular cognitive impairment no dementia (VCIND) group (n＝56) and vascular dementia (VD) group (n＝40) according to the degree of VCI. The levels of serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and plasma homocysteine (Hcy) were compared among the three groups, and the above indexes before and after treatment were compared in VCIND group and VD group. Furthermore, taking whether CSVD merges VCI as dependent variable, indicators with statistical differences in univariate analysis as independent variables, multivariate Logistic regression analysis was performed. Results The levels of serum hs-CRP, IL-6, IL-1β and TNF-α in the VCIND group and the VD group were significantly higher than those in the WVCI group (P＜0.05), and the levels of above serum indexes in the VD group were significantly higher than those in the VCIND group (P＜0.05). Compared with before treatment, the levels of serum hs-CRP, IL-6, IL-1β and TNF-α in VCIND group and VD group decreased significantly after treatment (P＜0.05 or P＜0.01). The levels of serum ICAM-1 and plasma Hcy in the VCIND group and the VD group were significantly higher than those in the WVCI group (P＜0.01), while the levels of serum ICAM-1 and plasma Hcy in the VD group were significantly higher than those in the VCIND group (P＜0.05). Compared with before treatment, the levels of serum ICAM-1 and plasma Hcy in VCIND group and VD group significantly decreased after treatment (P＜0.01). The levels of serum IL-6, IL-1β, TNF-α, ICAM-1 and plasma Hcy were negatively correlated with Montreal Cognitive Assessment Score (P＜0.05). Logistic regression analysis showed that serum IL-6, IL-1β, TNF-α, ICAM-1 and plasma Hcy were independent risk factors for VCI. Conclusion Inflammatory factors such as IL-6, IL-1β and TNF-α are involved in the occurrence of cognitive dysfunction in patients with hypertension CSVD, and the higher the levels, the more serious the degree of VCI.

Abstract:Aim To investigate the effect of carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) on the expression of coxsackie and adenovirus receptor (CAR) and secondary myocardial injury after coxsackievirus B3 (CVB3) infection. Methods The overexpressed mouse CC1 recombinant virus was constructed, and the recombinant lentivirus pLVX-CEACAM 1-ZsGreen-Puro (rLV-CEACAM 1) was packaged and the biological titer of lentivirus was determined. It was divided into CC1 normal cell group, CC1 overexpression group, CC1 normal +CVB3 group and CC1 overexpression+CVB3 group. The apoptosis rate of cardiomyocytes was detected by AnnxinV-PE/ 7-AAD double staining in each group, and cell activity was detected by CCK8. The expression of CAR gene was detected by qPCR. The expression of CAR protein was detected by Western blot, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) were measured by ELISA. Results (1)Recombinant vector sequencing CEACAM1 showed a gene sequence connection, which proved mice CEACAM1 recombinant virus vector was built, determination of recombinant lentivirus was 1.5×1011 TU/L. (2)Apoptosis rate of cardiac myocytes in CC1 overexpression+CVB3 group was significantly higher than that in other groups, and the proliferation rate of cardiac myocytes was the lowest (P<0.05). (3)Relative expression of CAR gene was the highest in CC1 overexpression+CVB3 group, and the lowest in CC1 normal group. Relative expression of CVB3 was significantly higher in CC1 overexpression group than in CC1 normal group (P<0.05). (4)Level of TNF-α, IL-1β were higher in CC1 overexpression group, which increased significantly after CVB3 infection. Conclusion CC1 may promote the expression of CAR in cardiac tissue or cell after CVB3 infected cardiac myocytes. CAR might be a potential target for CC1 to regulate the process of cardiac injury caused by CVB3 infection.

Abstract:Atherosclerosis is a progressive lesion of the intima of large and medium-sized arteries, which is the main cause of cardiovascular and cerebrovascular diseases. At present, the treatment of atherosclerosis is not satisfactory. Finding a new and more effective therapeutic target is a hot topic in current medicine. CD47, as a widely expressed protein, can promote the occurrence and development of atherosclerosis in many ways by binding to a ligand signaling regulatory protein alpha or platelet reactive protein-1, for example, blocking the efferocytosis of apoptotic cells, promoting the apoptosis of endothelial cells, inhibiting the physiological function of nitric oxide, and increasing the production of cell adhesion factors. Inhibition of CD47 expression can block these pathways and delay or even reverse atherosclerosis, so CD47 may become an important target for future anti-atherosclerosis studies.

Abstract:Aim To explore the effect of anti-inflammation cytokine interleukin-37 (IL-37) on the expressions of nuclear factor-κB (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) activated by Toll-like receptor-4 (TLR4) in human coronary artery endothelial cells (HCAECs) and its mechanism. Methods After 3-5 generations of HCAECs culture, the experiment was carried out and divided into 3 groups:the control group, the IL-37 interference group and the IL-37 overexpression group. The IL-37 interference sequence was added into the IL-37 interference group and the IL-37 DNA overexpressed plasmid was added to the IL-37 overexpression group by liposome transfection. After incubation of 24 hours, the gene transfection efficiency was detected by real-time fluorescence quantitative PCR to determine the success of transfection. Each group was given TLR4 activator lipopolysaccharide (200 μg/L) for intervention. Western blot was used to detect the expression of ICAM-1 protein after intervention of 24 hours and the expressions of phosphorylated NF-κB protein at 0,0, 120 minutes after intervention. Results The expression of ICAM-1 protein increased after TLR4 activation in the control group. Compared with the control group, the ICAM-1 protein increased significantly after TLR4 activation in the IL-37 interference group (P＜0.05), but did not increase in the IL-37 overexpression group (P＞0.05). Compared with the control group, the expression of NF-κB protein was significantly increased at 0,0 and 120 minutes after TLR4 activation in the IL-37 interference group (P＜0.05), but the expression of phosphorylated NF-κB protein was not significantly elevated in the IL-37 overexpression group (P＞0.05). Conclusion IL-37 can inhibit the increase of inflammatory factor ICAM-1 by TLR4 activation in HCAECs, and its mechanism may be through the inhibition of the degree of NF-κB phosphorylation. The anti-inflammatory effect of IL-37 can prevent atherosclerosis.

Abstract:With the accelerated aging of society, the incidence of atherosclerosis(As) is increasing year by year. Now that the initial event of the atherosclerosis is endothelial damage, while lipid metabolism is a major risk factor for vascular injury. But now research shows that some non-lipid material also play an important role in the development of As, such as high homocysteine (HHCy), high blood sugar and high uric acid. These non-lipid factors play a major role in vascular endothelial cells, interference by expression of sticky molecule, changing the state of the pathophysiology of endothelial cells, leading to endothelial damage, contributing to the formation of As lesions. This paper describes some of the mechanisms that the changes of adhesion molecules in non-lipid factors induced atherosclerotic vascular endothelial injury, and describes some of the therapeutic intervention targets expression of adhesion molecules, which has important clinical significance for the treatment of atherosclerosis leading to coronary heart disease, myocardial infarction and other cardiovascular diseases.

Abstract:Aim To investigate the effect and possible mechanism of total flavones of dracocephalum moldavica (TFDM) on atherosclerosis lesions in apolipoprotein E gene deficient (ApoE－/－) mice. Methods ApoE－/－ mice were randomly divided into model group, simvastatin group and TFDM high, medium, low dose group, C57BL/6J mice were set as the normal control group. After treated for 12 weeks, the mice were sacrificed and plasma lipids were determined, the area of atherosclerotic plaques and the ratio of plaque area to aorta were measured by HE staining, the expressions of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), proliferating cell nuclear antigen (PCNA) in aortic atherosclerotic lesions were detected by immunohistochemistry analysis. Results Compared with the model group, the levels of triglyceride (TG) and low density lipoprotein cholesterol (LDLC) was decreased significantly in treatment group. The atherosclerotic lesions reduced and the ratio of plaque area to aorta decreased in TFDM groups. The expression of ICAM-1, VCAM-1 and PCNA were down-regulated by TFDM. Conclusion TFDM can inhibit atherosclerosis formation which involved in decreasing the level of plasma lipids and weakening the expression of ICAM-1, VCAM-1 and PCNA in the aorta wall.

Abstract:Aim To study the relationship between DNA methylation level of intercellular adhesion molecule 1(ICAM-1) and atherosclerosis (As) occurrence, development and changes of blood lipids. Methods The atherosclerosis patients (100 patients from Hui and Han ethnic with As) were confirmed by carotid artery Doppler ultrasound and the serum lipids were measured by ADVIA 2400 automatic biochemistry analyzer, ICAM-1 mRNA expression was determined by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The methylation status of ICAM-1 gene promoter region was examined using nest touch down methylation specificpolymerase chain reaction (nt-MSP). Results Compared with As patients from Han ethnic, ICAM-1 mRNA expression levels were promoted in Hui ethnic (P<0.001), and the levels of ICAM-1 promoter methylation was decreased in Hui ethnic (P<0.001). Compared with As patients from Hui ethnic, triglycerides (TG) concentrations was promoted in As patients from Han ethnic(P<0.001), and was negatively correlated with ICAM-1 promoter methylation (r=－0.5783, P<0.001). Conclusion ICAM-1 DNA hypomethylation is related to the occurrence and development of As and the changes of serum lipids in peripheral blood mononuclear cells of Hui patients.

Abstract:Aim To observe and evaluate the effect of intermittent hypoxia(IH) on plasma lipoprotein-associated phospholipase A2(Lp-PLA2), interleukin-6(IL-6) and vascular cell adhesion molecule-1(VCAM-1) by the rabbit model of chronic intermittent hypoxia and the atherosclerosis formation. Methods Using randomized controlled study, prospective animal, variance analysis and so on. 36 New Zealand White rabbits(4 months old) were divided into two groups randomly. According to intermittent hypoxia time at 4, 8, 12 weeks, intermittent hypoxic group and control group were divided into 3 groups separately. There were 3 groups in the control group(C1, C2, C3) and the intermittent hypoxia group(IH1, IH2, IH3). There were 6 rabbits in each groups. Intermittent hypoxia group were placed in hypoxic chamber to treat by intermittent hypoxia for 8 hours per day. Weighting is at the fourth week, eighth week and twelfth week separately. The content of Lp-PLA2, IL-6 and VCAM-1 was tested by ELISA method. At the same time, the abdominal aorta was stained by HE staining to observe the formation of atherosclerosis. Results (1) The plasma levels of Lp-PLA2, IL-6 and VCAM-1 increased as time among IH1, IH2, IH3 and all control groups(P<0.05), which was the most obvious at 12th week.(2) At the 4th week, 8th week and 12th week, the plasma levels of Lp-PLA2, IL-6 and VCAM-1 had no difference in control groups.(3) The plasma levels of Lp-PLA2, IL-6 and VCAM-1 had a positive correlation with each other(P<0.05). The correlation coefficient was 0.75, 0.55 and 0.76 among Lp-PLA2, IL-6 and VCAM-1(P<0.001).(4) The formation of atherosclerosis in aortic tissue can be observed by HE staining after intermittent hypoxia intervention. Conclusion The plasma levels of Lp-PLA2, IL-6 and VCAM-1 was increased by intermittent hypoxia and had a correlation. IH may mediate the aggregation of inflammatory cytokines to lead to vascular endothelial injury and participate the formation of atherosclerosis.

Abstract:Aim To observe the change of serum Visfatin level in patients with unstable angina (UA); To investigate the correlation between serum Visfatin and soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1). Methods The changes of serum Visfatin, sVCAM-1 and sICAM-1 levels were detected by using quantitative sandwich enzyme-linked immunosorbent assay in 80 UA patients (UA group), 68 patients with stable angina (SA group) and and 60 healthy subjects (control group). Other clinical biochemical indexes were routinely detected at the same time. In the UA group, the relationships between serum Visfatin and sVCAM-1, sICAM-1, high-sensitivity C-reactive protein (hs-CRP), other biochemical indexes were analysed by Pearson correlation test. Results The levels of serum Visfatin, sVCAM-1 and sICAM-1 in UA group were significantly higher than those in SA group and control group (P＜0.05, P＜0.01). In the UA group, serum Visfatin level was significantly positively correlated with sVCAM-1 (r＝0.332, P＜0.01), sICAM-1 (r＝0.479, P＜0.01), hs-CRP (r＝0.521, P＜0.01), but there was no significant correlation between serum Visfatin and waist circumference, body mass index, blood pressure, other biochemical indexes. There were no significant differences in serum Visfatin, sVCAM-1 and sICAM-1 levels between the SA group and the control group (P＞0.05). Conclusions The level of serum Visfatin is significantly increased, and is positively correlated with sVCAM-1, sICAM-1 and hs-CRP in UA patients. It is suggested that serum Visfatin is closely related to vascular endothelial injury and plaque instability, so it may be a marker of vascular endothelial injury.

Abstract:Aim To observe relationship between high-sensitivity C-reactive protein （hs-CRP）,high mobility group box-1 protein （HMGB1） and intercellular adhesion molecule-1 （ICAM1） with GRACE score,and to clarify the value of hs-CRP,HMGB1 and ICAM1 in estimating the criticality of non-ST segment elevation acute coronary syndrome （NSTEACS） patients.Methods According to the GRACE score NSTEACS patients were divided into different groups: risk group （≤108 scores）,middle risk group （109～140 scores）,high risk group （＞140 scores）,and 20 volunteers negative in coronary angiography （CAG） were as the control group. The levels of hs-CRP,HMGB1,ICAM1 in each group were detected,and the indexes were compared among various groups. Relationship between the indexes and GRACE score was analyzed.Results The levels of hs-CRP,HMGB1,ICAM1 in four groups were significantly different from each other. At the same time,hs-CRP,HMGB1,ICAM1 have significantly positive relationship with GRACE score （r＝0.498,0.561,0.526）. Conclusion hs-CRP,HMGB1,ICAM1 have intimate connection with GRACE score,and have practical value in estimating the criticality of NSTEACS patients.