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Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction (MI). MicroRNA-146b (miR-146b) is an active regulator of immunomodulation, but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following MI remain largely unknown. Herein, miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia patients. Gain- and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac cells. Overexpression of miR-146b-5p activated fibroblast proliferation, migration, and fibroblast-to-myofibroblast transition, impaired endothelial cell function and stress survival, and disturbed macrophage paracrine signaling. Interestingly, the opposite effects were observed when miR-146b-5p expression was inhibited. Luciferase assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1 (IRAK1) and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1). Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death, and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine MI models. Local inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following MI.
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Objective To explore the effectiveness and compliance of ketogenic-diet(KD) treatment for infantile spasm(IS).Methods Ninety-eight IS patients who were treated with KD in Wuhan Children's Hospital from March 2009 to June 2015 were analyzed by using retrospective case-control study,the patients were divided into 4 groups:newly diagnosed IS patients group (group A,including 24 patients),one antiepileptic drug (AEDs) failure IS patients (group B,including 28 patients),two and more AEDs failure IS patients (group C,including 29 patients),and two or more AEDs combined with ACTH failure IS patients(group D,including 17 patients).The spasm-free andretention rates after 3,6 and 12 months KD treatment were compared among these groups.Results Overall retention rate was 80.6％ (79/98 cases),69.4％ (68/98 cases),and 42.9％ (42/98 cases)at 3,6,12 months,respectively.The 3-month retention rate in group A,B,C and D was 83.3 ％ (20/24 cases),78.6％ (22/28 cases),82.7％ (24/29 cases) and 76.4％ (13/17 cases) respectively,and there was no significant difference among these groups (P ＞ 0.05).The 6-month retention rates in each group was 75.0％ (18/24 cases),67.9％ (19/28 cases),68.8％ (20/29 cases) and 65.0％ (11/17 cases) in sequence,and there was also no significant difference among these groups(P ＞0.05).The 12-month retention rate was 54.2％ (13/24 cases),21.4％ (6/28 cases),48.3％ (14/29 cases) and 52.9％ (9/17 cases) in group A,B,C and D in sequence,the 12-month retention rate of group B was significantly lower than that of other 3 groups,and the differences were statistically significant(x2 =5.973,4.508,4.727,all P ＜ 0.05),and there was no significant difference among the A,C,D groups (all P ＞ 0.05).The spasm-free rate at 3,6,12 months of KD treatment was 19.4％ (19/98 cases),20.4％ (20/98 cases),30.6％ (30/98 cases).The 3-month spasm-free rate in A,B,C,D groups were as follow:41.7％ (10/24 cases),14.3％ (4/28 cases),10.3％ (3/29 cases),11.8％ (2/17 cases),respectively.The 3-month spasm-free rate in group A was significantly higher than that of other 3 groups,and the differences were statistically significant (x2 =10.238,9.219,6.697,all P ＜ 0.05),but there was no significant difference among the B,C,D groups (all P ＞ 0.05).The 6-month spasm-free rates were 41.7％ (10/24 cases),14.3％ (4/28 cases),13.8％ (4/29 cases),and 11.8％ (2/17 cases) in group A,B,C and D in order,and the spasm-free rate in group A was significantly higher than that of other 3 groups,and the differences were statistically significant(x2 =4.924,5.249,4.298,all P ＜ 0.05),but there was no significant difference among the A,C,D groups (all P ＞ 0.05).The 12-month spasm-free rates were 54.2％ (13/24 cases),21.4％ (6/28 cases),24.1％ (7/29 cases),and 23.5 ％ (4/17 cases) in group A,B,C and D,and the spasm-free rate in group A was significantly higher than that in other 3 groups,and the differences were statistically significant(x2 =8.354,7.923,4.364,all P ＜ 0.05),but there was no significant difference among the A,C,D groups (all P ＞ 0.05).Conclusions The spasm-free rate of KD therapy for newly-diagnosed IS is higher than that of IS patients whose drug-therapy failed.KD therapy may be the top priority for IS patients and part of those patients whose drug-therapy failed can still get seizure-free with KD diet.
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Objective To develop a better method for preparation of porcine model of acute myocardial infarction by permanent occlusion of the left circumflex coronary artery and minimally invasive surgery, evaluate its validity and stability, and explore its application in experimental studies of ischemic heart diseases.Methods 25 healthy female 3-month-old Bama minipigs, body weight 25±3 kg, were used in this study.The porcine model of myocardial infarction was established by minimally invasive surgery and the left circumflex artery ligation at the site of OM1 posterior position under general anesthesia.Heart function was assessed by echocardiography at 15 min before surgery, 1 hour and 4 weeks after surgery.Pathological examination was performed at 4 weeks after the left circumflex artery occlusion.The mortality and cause of death were statistically analyzed.Results The 1-hour and 4-week postoperative cardiac function was considerably decreased, showing a decreased ejection fraction from 64.2±4.6% to 48.2±5.3% (1hour after MI) and 49.7±6.1% (4 weeks after MI) (P<0.01).Pathological examination revealed that the ventricular wall was thinner and the amount of collagens was increased in the infracted area.The ventricular fibrillation rate at 1-hour after myocardial infarction was 17.3% and the infarction area was 19.2%.Conclusions A pig model of acute myocardial infarction can be prepared by our modified left circumflex coronary artery ligation at the obtuse marginal artery (OM1) and minimally invasive surgery.This model exhibits advantages such as minimal surgical trauma, high stability of the model, and low mortality, therefore, provides an ideal and economic animal model for experimental studies on acute ischemic heart diseases.
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Objective To investigate the possible roles of Langerhans cells(LCs) and plasmacytoid dendritic cells(pDCs)in the pathogenesis of condyloma acuminatum(CA). Methods Tissue specimens were obtained from the lesions of 23 patients with CA and from perilesional normal skin of 13 of the 23 patients. The expressions and distribution of CD1a, CD2AP and CD123 were analyzed using the streptavidin-peroxidase (SP) immunohistochemical method. Statistical analysis was carried out to compare the density and percentage of CD1a + LCs, CD2AP + pDCs and CD123 +pDCs between lesional skin and perilesional normal skin. Results Most CD1a + LCs were observed in the prickle cell layer of the epidermis, and a few in the papillary layer of the dermis. There was no significant difference in the density or percentage of CD1a+ LCs in the epidermis or dermis between the lesional and perilesional skin specimens (all P > 0.05). CD2AP + pDCs and CD123 + pDCs were distributed mainly in the papillary layer of the dermis, and their density and percentage were significantly higher in the lesional than in the perilesional skin specimens (all P < 0.05). Conclusion Human papillomavirus infection may affect the quantity of pDCs but not LCs in local mucous membranes.
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Objective To evaluate the effects of hydroxyethyl starch (HES) on the renal function and blood coagulation of patients with acute pancreatitis (AP). Methods 151 patients with acute pancreatits were divided into treatment group (treated with HES, n=62) and control group (treated with crystalloid solutions, n =89). The two groups were compared by retrospective analysis of the indices such as serum creatinine (Scr), blood urea nitrogen (Bun), platelet count(Plt), prothrombin time activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT) and fibrinogen (FIB) before and after treatment. Results Before hospitalization, there were insignificant differences in respect of Scr and Bun in the two groups respectively. But at discharge, Scr and Bun in the treatment group were significantly increased (P<0.05), while Bun was significantly decreased 24 h right after infusion of crystalloid solutions in the control group (P<0.05). There were no differences between the two groups in terms of Scr and Bun. As for indices of coagulation, APTT in the treatment group was significantly increased after infusion of HES (P<0.05). The hospital stay in the treatment group was longer than the control group (P < 0.05). Conclusions HES may adversely affect renal function and intrinsic pathway of blood coagulation of patients with AP. Renal function and blood coagulation should be monitored when using HES.
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Objective To observe the variation of plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG),a biomarker of oxidative DNA damage,in patients with Alzheimer's disease (AD) versus vascular dementia (VaD),and to investigate the important role and the difference of oxidative DNA damage in the initiation and development of AD and VaD.Methods 35 AD patients,28 VaD patients and 23 age and sex matched normal controls were enrolled in this study.Plasma 8-OHdG was measured by an enzyme-linked immunosorbent assay (ELISA) method.Cognition function in AD and VaD patients was measured by Mini-Mental State Examination (MMSE).Results There were significant differences in plasma 8-OHdG concentrations among AD,VaD and control groups [(601.8±266.0) ng/L,(1748.0±665.6)ng/L,(352.0±94.5)ng/L,respectively,P＜0.001].Plasma 8-OHdG was significantly higher in VaD group than in control group (P＜0.05).While,there was no significant difference in plasma 8OHdG concentration between AD group and control group (P＞0.05).Plasma 8-OHdG was significantly higher in VaD group than in AD group (P＜0.05).Plasma 8-OHdG levels were positively related with age in AD,VaD and control groups (r=0.661,0.702,0.719,respectively,all P％0.01).No correlations were found between plasma 8-OHdG concentration and education level among the three groups (all P＞0.05).AD and VaD patients were subgrouped according to the risk factors including gender,smoking,hypertension,diabetes,hyperlipidemia.There were no significant differences in plasma 8-OHdG level between the subgroups (all P＞ 0.05).After adjusting for sex,age,education level,smoking,hypertension,hyperlipidemia and diabetes,logistic regression analysis showed that the probability of high plasma 8-OHdG level was higher in VaD group than in AD and control groups.Plasma 8-OHdG level had a negative correlation with MMSE score in VaD group (r=-0.592,P＜0.01),while no correlation was found between plasma 8-OHdG level and MMSE score in AD group (r =-0.122,P＞ 0.05).Conclusions There is significant oxidative DNA damage in VaD patients.Plasma oxidative DNA damage is more serious in VaD patients than in AD patients and healthy people.Plasma 8-OHdG level,a oxidative DNA damage biomarker,has a significant correlation with the degree of cognition impairment in VaD patients.
