AIM:To investigate the effects of angiotensin II ( Ang II) on the immune maturation and the oxi-dized low-density lipoprotein (Ox-LDL)-uptaking capacity of human monocyte-derived dendritic cells (DCs).METH-ODS:Human peripheral blood mononuclear cells were isolated by density gradient centrifugation , and the monocytes were purified by positive selection with anti-CD14 magnetic beads.After cultured with rhGM-CSF (100 μg/L) and rhIL-4 (50μg/L) for 5 d, the monocytes differentiated into immature DCs .On the 6th day of the culture, the cells were treated with various concentration levels of Ang II or pretreated with losartan .The immunophenotypic expression of HLA-DR and CD83 was analyzed by flow cytometry .The secretion levels of IL-12 and IFN-γin the culture supernatants were measured by ELISA.Furthermore, DCs were incubated with DiI-labelled Ox-LDL.The DiI-Ox-LDL-incorporated fraction was investiga-ted by flow cytometry .The mRNA expression of 3 scavenger receptors , scavenger receptor A ( SR-A) , CD36 and lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), was examined by real-time PCR.RESULTS: Ang II induced the maturation of human monocyte-derived DCs, stimulated the expression of CD83 and HLA-DR, and promoted the secre-tion of IL-12 and IFN-γ, which were suppressed by losartan .Furthermore, Ang II increased the Ox-LDL-uptaking capacity of DCs, which was partially reduced by losartan .The incubation of DCs with Ang II enhanced the mRNA expression of LOX-1 in a dose-dependent manner , which was reduced by losartan .However, the expression of SR-A and CD36 was not changed .CONCLUSION:Ang II promotes the immune maturation of human monocyte-derived DCs and increases the up-take of Ox-LDL probably through the up-regulation of LOX-1 expression.

Objective To observe the effects of eluting stents coated with arsenic trioxide(As2O3)and suspended in poly-L-lactic acid(PLLA)on expression of monocyte chemoattractant protein-1 (MCP-1)and interleukin-6(IL-6)and to assess the effects of As2O3 eluting stents on local inflammatory reaction in injured coronary arteries in pigs. Methods Bare metal stents,rapamycin eluting stents and As2O3-eluting stents were randomly and double-blindly implanted into the anterior descending branches,circumflex branches and right coronary arteries in eight pigs.Animals were sacrificed and coronary arteries were isolated 7 days after stents implantation.The expression levels of protein and mRNA of MCP-1 and IL-6 were determined by Western blot analysis and reverse transcription polymerase chain reaction(RT-PCR),and the inflammatory cell infiltration was observed by HE staining and immunohistochemistry. Results Compared to bare metal stents,As2O3-eluting stents and rapamycin-eluting stents identically and markedly inhibited the protein expression level of MCP-1(0.421±0.055 and 0.406±0.042 vs.0.857±0.053,P＜0.01)and IL-6(0.151±0.032 and 0.146±0.051 vs.0.551±0.032,P＜0.01)and correspondingly lowered the mRNA expression level of MCP-1(0.338±0.047 and 0.327±0.051 vs.0.724±0.027,P＜0.01)and IL-6(0.531±0.052 and 0.523±0.061 vs.1.015±0.041,P＜0.01),and significantly reduced the inflammatory cell infiltration of injured coronary arteries in pigs. Conclusions As2O3-eluting stents can effectively inhibit the expressions of MCp-1 and IL-6 and reduce the inflammatory cell infiltration of injured coronary arteries in pigs.

Objective: To observe the changes of circulating fractalkine and its receptor CX3CR1 level in patients with chronic congestive heart failure (CHF).
Methods: Our work included 2 group, CHF group, n=55 patients and Control group, n=25 healthy subjects. Plasma level of soluble fractalkine (sFKN) was measured by ELISA, CX3CR1 in peripheral blood mononuclear cell was examined by lfow cytometry method. The relationship between sFKN and NT-proBNP was studied.
Results: Compared with Control group, CHF group had increased sFKN level, P=0.004, and the patients with NYHY III, IV were more than NYHY II, and CHF group also had the higher CX3CR1 expression (14.7 ± 8.1), P<0.05. The CX3CR1 level increased accordingly with NYHY classiifcation, as the patients with NYHY II, CX3CR1 was at (25.1 ± 12.4), P=0.03 compare with Control group;with NYHY III, CX3CR1 was at (37.3 ± 11.0) , P=0.04 compared with NYHY II;with NYHY IV, CX3CR1 was at (41.7 ± 11.1), P=0.009 compared with NYHY II. The circulating sFKN level was positively related to pro-BNP level (r=0.364, P<0.01).
Conclusion: The circulating FKN l and its receptor CX3CR1 might be involved in pathogenesis of immune-inlfammatory pathogenesis in CHF patients.

Objective: To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability. Methods: A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels. Results: Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P < .01). Transwell assays showed that TF3 promoted the migration of HUVECs, but inhibited the migration of MC3T3-E1 cells. Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules. Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA, SPOCD1, NGF, and NGFR in HUVECs. In MC3T3-E1 cells, the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment. Conclusion TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.

Objective To investigate the altered spontaneous cerebral activity in patients with type 2 diabetic retinopathy (T2DR). Methods Twenty-one patients with T2DR and sixteen healthy control subject underwent rs-fMRI scans,and the data were analyzed statistically using regional homogeneity(ReHo)method to observe the change of ReHo value.Results Compared to the control group,the T2DR group showed significantly increased ReHo value in the right occipital gyrus,occipital gyrus,inferior occipital gyrus and lingual gyrus regions (t=5.30,P＜0.05,voxel＞30,AlphaSim corrected),and significantly decreased ReHo value in the left posterior cingulate,margin lobe,right inferior parietal lobule,superior temporal gyrus and hippocampus (t=-4.01,-4.86,P＜0.05,voxel＞30, AlphaSim corrected).Conclusion The patients with T2DR showed significantly increased ReHo values in the brain visual cortex and visual pathway that were associated with the injury of brain function regions.It is of important value to evaluate brain dysfunction in patients with T2DR using ReHo method of rs-fMRI.

OBJECTIVEDendritic cells an hyperinsulinemia are both implicated in the pathogenesis of atherosclerosis. The aim of this study is to explore the effect of high concentration of insulin on the maturation of monocyte-derived dendritic cells (MoDCs) and related signal transduction pathways.

METHODSHuman monocytes were purified (over 98%) using Anti-CD14 micro-beads and cultured for 5 days with DC Cellgro medium containing rhGM-CSF (100 microg/L) and rhIL-4 (20 microg/L). Immature DC were then incubated with insulin of various concentrations (0, 1, 10, 100 nmol/L) for 24 hours in the presence or absence of LY294002 (PI3K inhibitor) or PD98059 (MAPK inhibitor). Immunophenotypic expression of CD86 and CD83 were detected using flow cytometry. Endocytosis function of the MoDCs was evaluated using FITC-Dextran and MoDCs secretion IL-12, IFN-gamma and TNF-alpha were measured by ELISA.

RESULTSInsulin induced significantly higher CD83 and CD86 expressions on MoDCs in a dose-dependent manner. The endocytosis function of MoDCs were significantly inhibited and cytokine secretions of IL-12, IFN-gamma and TNF-alpha significantly increased by 10 nmol/L and 100 nmol/L insulin. These effects could be blocked by the LY294002 and PD98059.

CONCLUSIONHyperinsulinemia contributed to atherosclerosis via stimulating immune maturation of MoDCs via both PI3K and MAPK pathways.

Cell Differentiation ; drug effects ; immunology ; Cells, Cultured ; Cytokines ; metabolism ; Dendritic Cells ; drug effects ; immunology ; metabolism ; Humans ; Insulin ; administration & dosage ; pharmacology ; Monocytes ; cytology ; Phagocytosis ; drug effects ; Signal Transduction

Objective To investigate the correlation analysis of serum autotaxin(ATX),tenascin-C(TN-C)and ventricular remodeling indexes in elderly patients with dilated cardiomyopathy(DCM)with heart fail-ure(HF)and their effects on prognosis.Methods 153 elderly patients with DCM with HF who were admit-ted to the 904th Hospital of the Joint Logistic Support Force from January 2020 to January 2022 were selected as DCM with HF group,and 100 elderly patients with simple DCM in the same hospital during the same peri-od were selected as DCM group and 100 healthy elderly individuals who underwent physical examination were selectedas control group.Serum ATX and TN-C levels were detected by enzyme-linked immunosorbent assay,and ventricular remodeling indexes[left ventricular end-diastolic diameter(LVEDD),left ventricular end-sys-tolic diameter(LVESD),and left ventricular ejection fraction(LVEF)]were detected by echocardiography.The correlation between serum ATX,TN-C levels and ventricular remodeling indexes in elderly patients with DCM with HF were analyzed by Pearson correlation analysis.Elderly patients with DCM with HF were fol-lowed up for 1 year,patients were divided into poor prognosis group and good prognosis group according to the prognosis.The influencing factors of poor prognosis in elderly patients with DCM with HF were analyzed by univariate and multivariate logistic regression analysis,the predictive value of serum ATX and TN-C levels for poor prognosis in elderly patients with DCM with HF was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of ATX and TN-C in DCM combined HF group were higher than those in DCM group and control group,and the difference was statistically significant(P＜0.05).Serum ATX and TN-C levels in DCM group were higher than those in control group,and the difference was statistically significant(P＜0.05).LVEDD and LVESD in DCM with HF group were higher than those in DCM group and control group,and LVEF was lower than those in DCM group and control group,the difference was statis-tically significant(P＜0.05).Pearson correlation analysis showed that serum ATX and TNC levels in elderly patients with DCM with HF were positively correlated with LVEDD and LVESD,and negatively correlated with LVEF(P＜0.05).Univariate analysis showed that HF disease course,NYHA cardiac function grade,NT-proBNP,ATX and TN-C were the influential factors for poor prognosis in elderly patients with DCM with HF(P＜0.05).Multivariate Logistic regression analysis showed that the independent risk factors for poor prognosis in elderly patients with DCM with HF were NYHA cardiac function grade&ge;Ⅲ and the increase of NT-proBNP,ATX and TN-C(P＜0.05).ROC curve analysis showed that the area under the curve and 95％CI of serum ATX and TNC alone and combined for poor prognosis in elderly patients with DCM with HF were 0.743(0.576-0.911),0.721(0.551-0.911)and 0.808(0.690-0.912),respectively.Conclusion The elevated levels of serum ATX and TN-C in elderly patients with DCM with HF may be relat-ed to ventricular remodeling and poor prognosis,and have certain predictive value for the prognosis of elderly patients with DCM with HF.

Objective:To analyze the frequency and alteration of circulating dendritic cells (DCs) and subtypes in patients with ST‐elevated acute myocardial infarction(AMI) .Methods:A total of 17 patients with ST‐elevated AMI(AMI group) and 14 pa‐tients with stable angina pectoris(SAP) as SAP group and 15 people with normal coronary angiogram with matched age and gender(control group) were enrolled .The absolute number and percentage in peripheral blood mononuclear cells of circulating DCs ,myeloid dendritic cell(mDC) and plasmacytoid dendritic cell(pDC) in the three groups were detected using the 3‐colure staining flow cytometry .The levels of interleukin‐6(IL‐6) and tumor necrosis factor‐α(TNF‐α) were detected with enzyme‐linked immunosorbent assay .In the AMI group ,these indexes were measured on the 7th day after the attack .Results:The per‐centage of circulating DCs in peripheral blood mononuclear cells and the absolute number of DCs ,the percentage of circulating mDC and pDC in peripheral blood mononuclear cells and the absolute numbers of mDC and pDC and mDC/pDC ratio in the AM I group on the day of attack(<24 h) were significantly lower than those in the control group and the SAP group(P<0 .01 or 0 .05) .In the AMI group ,on the 7th day after the attack , the percentages of DCs ,mDC and pDC in peripheral blood mononuclear cells and the absolute numbers of DCs ,mDC and pDC and mDC/pDC ratio were higher than those on the day of attack (P<0 .01 or 0 .05) .The level of IL‐6 and TNF‐αin the AMI group on the day of attack were significantly higher than those in the control group and SAP group(P<0 .05) ,and the level of IL‐6 decreased on the 7th day after the attack in the AMI group (P<0 .05) .But there was no significant difference in the percentage of DCs ,mDC and pDC in peripheral blood mononu‐clear cells and the absolute numbers and mDC/pDC ratio between the control group and the SAP group(P>0 .05) .Conclu‐sions:Circulating mDC and pDC are significantly reduced in patients on the day of attack of AM I ,and it can increase to nearly normal on the 7th day after attack .It indicates that the possibility of DCs recruits into coronary plaques and improve the forma‐tion of unstable plaque .

Sympathetic remodeling after myocardial infarction is presented as denervation, sympathetic nerve sprouting and sympathetic hyperinnervation, and is closely related to ventricular tachyarrhythmias and even sudden cardiac death at convalescence in patients with myocardial infarction. This article reviews the anatomic structure, morphology and functional remodeling of cardiac sympathetic nerve, as well as its role in healed myocardial infarction identification, which may provide references for forensic research.
Atrial Remodeling ; Forensic Sciences ; Heart ; Humans ; Myocardial Infarction/pathology*

Objectives To compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor ( G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia. Methods Eighteen Swine underwent placement of ameriod constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups ( n = 6 each) : ( 1 ) administration of vehicle (control) , (2) hypodermic injection of G-CSF(5 μg · kg-1·d-1 ) for five days (IH) , and (3) intracoronay injection of a bonus G-CSF (60 μg/kg) (IC). Coronary angiogram, cardiac MRI, and 18F-FDG-SPECT/99mTc-SPECT ( DISA-SPECT ) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diatolic volume ( LVEDV ) , left ventricular end-systolic volume ( LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR. Results MRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronay injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis. Conclusions Both intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.