Objective To explore the protective effect of miR-374c-5p on hydrogen peroxide(H2O2)-induced apoptosis of human umbilical vein endothelial cells(HUVECs).Methods HUVECs were cultured in vitro and the harvested cells were divided into four groups:control group,H2O2 group,H2O2+miR-374c-5p mimics trans-fection group,and H2O2+miR-374c-5p inhibitor transfection group.Cell activity was assessed by CCK-8 prolifer-ation rate assay,apoptosis was detected by TUNEL staining microscopy.Expression of miR-374c-5p and Fas mRNA by RT-qPCR,and Fas protein in HUVECs by was detected by Western blot.Results Proliferation of HUVECs was significantly inhibited(P＜0.001);H2O2 was significantly increased as compared with the H2O2 in-tervention group(P＜0.001);Proliferation in H2O2+miR-374c-5p inhibitor transfection group was significantly increased as compared to H2O2 intervention group(P＜0.001).Conclusions miR-374c-5p protectes the HUVECs against apoptosis induced by H2O2.

Objective:To investigate the effect of digoxin on bleomycin-induced pulmonary fibrosis in mice, and investigate its possible mechanism through in vitro and in vivo experiments. Methods:① In vivo experiment: 60 C57/BL6J mice were randomly divided into control group, pulmonary fibrosis model group (model group), pirfenidone (300 mg/kg) group, digoxin 1.0 mg/kg and 0.2 mg/kg groups, with 12 mice in each group. The pulmonary fibrosis model of mice was reproduced by single intratracheal infusion of bleomycin (5 mg/kg). The control group was given the same amount of sterile normal saline. From the next day after modeling, each group was received corresponding drugs by intragastric administration once a day for 28 days. Control group and model group were given the same amount of normal saline. The mice were sacrificed and the lung tissue was collected to detect the lung coefficient. After hematoxylin-eosin (HE) and Masson staining, the lung tissue morphology and collagen changes were observed under light microscope. Immunohistochemistry was used to detect the positive expressions of α-smooth muscle actin (α-SMA) and extracellular matrix (ECM) collagen (COL-Ⅰ and COL-Ⅲ) in lung tissue. The protein expressions of ECM fibronectin (FN), transforming growth factor-β (TGF-β) and phosphorylation of Smad3 (p-Smad3) in lung tissue were detected by Western blotting. ② In vitro experiment: human embryonic lung fibroblast-1 (HFL-1) cells were cultured and divided into blank control group, fibroblast activation model group (model group), pirfenidone (2.5 mmol/L) group and digoxin 100 nmol/L and 50 nmol/L groups when cell density reached 70%-90%. After 3-hour treatment with corresponding drugs, except blank control group, the other groups were treated with TGF-β for 48 hours to establish fibroblast activation model. The expressions of α-SMA, FN and p-Smad3 proteins and the phosphorylations of phosphatidylinositol-3-kinase (PI3K)/Akt pathway proteins PI3K and Akt (p-PI3K, p-Akt) were detected by Western blotting. Results:① In vivo, compared with the control group, the alveolar structure of mice in the model group was significantly damaged, a large number of inflammatory cells infiltrated, collagen deposition in the lung interstitium was increased, the deposition of ECM in the lung tissue was also increased, and the expressions of α-SMA, FN, TGF-β and p-Smad3 protein were increased, indicating that the model of bleomycin-induced pulmonary fibrosis in mice was successfully prepared. Compared with the model group, digoxin significantly inhibited airway inflammation and collagen fiber deposition, reduced ECM deposition, and decreased the protein expressions of α-SMA, FN, TGF-β and p-Smad3, while the effect was better than that of the pirfenidone group, and the digoxin 1.0 mg/kg group had a better effect except FN [α-SMA ( A value): 5.37±1.10 vs. 9.51±1.66, TGF-β protein (TGF-β/GAPDH): 0.09±0.04 vs. 0.33±0.23, p-Smad3 protein (p-Smad3/GAPDH): 0.05±0.01 vs. 0.20±0.07, all P < 0.01]. ② In vitro, compared with the blank control group, the expressions of FN, α-SMA, p-Smad3 and PI3K/Akt signaling proteins in the model group were increased, indicating that the fibroblast activation model induced by TGF-β was successfully reproduced. Compared with the model group, digoxin significantly inhibited fibroblast activation, and decreased the expressions of FN, α-SMA, p-Smad3, and PI3K/Akt pathway proteins, moreover, the effect was better than that of the pirfenidone group, and decreased FN, SMA and p-Akt protein expressions were more obvious in digoxin 100 nmol/L group [FN protein (FN/GAPDH): 0.21±0.15 vs. 0.88±0.22, α-SMA protein (α-SMA/GAPDH): 0.20±0.01 vs. 0.50±0.08, p-Akt protein (p-Akt/GAPDH): 0.30±0.01 vs. 0.65±0.10, all P < 0.01]. Conclusion:Digoxin could suppress the pulmonary fibrosis in mice induced by bleomycin, which might be associated with the regulation of fibroblast activation via suppressing PI3K/Akt signaling pathway in a dose-dependent manner.

Objective: To determine the level of Soluble Suppression of Tumorigenicity-2 (sST2) in patients with heart failure(HF) and atrial fibrillation (AF), and to explore its diagnostic and prognostic value in patients with HF and AF. Methods: A prospective cohort study was carried out to investigate the data of 185 HF patients who were hospitalized between January 2018 and June 2018 in department of cardiology or department of cardiac care unit in TEDA International Cardiovascular Hospital. And according to whether they had atrial fibrillation before admission, we categorized patients into: HF with sinus rhythm (HF-SR, n=90) and HF with AF(HF-AF, n=95). Meanwhile, 40 healthy controls were collected. Baseline data of HF-SR and HF-AF groups and plasma sST2 levels in different ejection fraction groups were compared. Plasma sST2 level was determined by enzyme-linked immunosorbent assay(ELISA). Statistical methods such as nonparametric test and Spearman correlation analysis were used. The receiver operating characteristic curve was applied to evaluate the diagnostic value of sST2 in HF-SR and HF-AF groups. And by using the COX risk model, Multi-factor COX analysis was used to analyze the prognosis of patients. Results: Compared with healthy controls, the median (P₂₅, P₇₅) of Plasma sST2 levels in HF patients increased remarkably [32.93 (20.31-51.39) ng/mL vs 15.99(7.97-22.69) ng/mL, Z=-4.373, P<0.001]. Patients with HF-AF group had significantly higher test results [39.86 (27.20-59.21)] ng/mL than HF-SR group [24.74 (14.83-44.11)] ng/mL, Z=-6.783, P<0.001].In the HFmrEF and HFpEF subgroups, the plasma sST2 level of patients in the HF-AF group was higher than that in the HF-SR group (Z=-2.381, P=0.017; Z=-3.701, P<0.001).Spearman correlation analysis showed that, in HF-AF patients, plasma sST2 level was positively correlated with diastolic blood pressure, Hypertension, New York Association (NYHA) cardiac function classification Ⅲ to Ⅳ, white blood count(WBC), and the level of Alanine Aminotransferase (ALT), Υ-glutamine transaminase (Υ-GT), B-type natriuretic peptide (BNP) (r>0, P<0.05).Also, there is a negative correlation between sST2, left ventricular ejection fraction (LVEF) and estimated Glomerular Filtration Rate (eGFR) (r<0, P<0.05). At ROC analysis, sST2 showed predictive value in both HF-AF and HF-SR group, with an optimal cut-off value of 25.33 ng/mL(AUC 0.872, 95%CI: 0.805-0.935, P<0.001, sensitivity 81.1%, specificity 87.5%) and 23.34 ng/mL(AUC 0.665, 95%CI: 0.570-0.761, P<0.001, sensitivity 55.6%, specificity 77.5%).The AUC of BNP and sST2 in differential diagnosis of HF-SR and HF-AF was 0.604 and 0.699, respectively, and the AUC of sST2 was higher than that of BNP. Multi-factor COX analysis indicated that plasma sST2 level, BNP, NYHA cardiac function grading could be risk factors for cardiac events in HF patients. Plasma sST2, left atrial diameter (LA-D), and associated cardiomyopathy are risk factors for cardiac events in patients with HF-AF. The incidence of cardiac events in HF patients with sST2≥20.31 ng/mL was significantly higher than that of patients with sST2<20.31 ng/mL (χ²=7.625, P=0.006). The incidence of cardiac events in HF-AF patients with plasma sST2≥39.86 ng/mL was significantly higher than that in patients with sST2<39.86 ng/mL (χ²=4.287, P=0.038). Conclusions The plasma sST2 level in patients with HF-AF is significantly higher than that both in HF-SR and healthy controls. The diagnostic value of plasma sST2 in patients with HF-AF is higher than that in patients with HF-SR. It is suggested that sST2 are more valuable for the differential diagnosis of HF-SR, HF-AF than BNP. HF-AF Patients with plasma sST2 ≥ 39.86 ng/mL are prone to cardiovascular events.

Objective To explore the association between the polymorphism rs671 site of the acetaldehyde dehydrogenase 2 (ALDH2) gene and H-type hypertension in the elderly in Han nationality in Qingdao.Methods Totally 406 patients aged 60-90 years with primary hypertension were randomly selected in the study.Serum levels of homocysteine(Hcy),folate and vitamin B12 were determined and all patients were divided into H-type hypertension group and non H-type hypertension group.Gene chip technology was used to analyze the ALDH2 (rs671) polymorphism,and the association between ALDH2 gene and H type hypertension was evaluated.Results Of all hypertensive participants,82.0％ (333/406) were in H-type hypertension,87.4％ (221/253) in male and 73.2％ (112/153) in female.The GA/AA genotype and A allele frequency were higher in H-type hypertension group than in non H-type hypertension group [37.2 ％ (124/333) vs.16.4 ％ (12/73) and 21.3％(71/333) vs.9.6％(7/73),P=0.001and 0.021].Serum Hcyleveland the prevalence of H type hypertension were higher in GA/AA genotype group than in GG genotype group(both P＜ 0.05).Logistic regression analysis showed that GA/AA genotype,gender (male),drinking,folate deficiency and increased systolic pressure were the risk factors for H-type hypertension (OR=3.17,2.14,2.37,0.75,1.03,respectively,all P＜ 0.05).Conclusions The genetic variation of ALDH2(rs671) may increase Hcy level by decreasing the levels of folate and vitamin B12.GA/AA genotype is a risk factor for H-type hypertension,and it contributes to H-type hypertension together with gender,drinking history,folate levels and systolic pressure.

OBJECTIVEA Meta-analysis was performed to assess the association of defective hepatic cytochrome P450 2A6 (CYP2A6) gene with smoking behaviors.

METHODSAll eligible studies published up to 2014 were searched out from PubMed, China National Knowledge Internet (CNKI), ISI Web of knowledge (ISI), vip citation databases (VIP), Chinese BioMedical Literature (CBM) and Elsevier Science Direct, searching words were "smok*","nicotine dependence","CYP2A6","cytochrome P450 2A6","polymorphism","mut*"and"varia*", while 436 articles were concluded. Meta-analysis was performed using Statal 3.1.

RESULTSA total of ten studies were finally included. We didn't find a significant effect of defective CYP2A6 gene on smoking initiation (fixed effect model (FEM): OR = 0.90, 95%CI: 0.78-1.03, I(2) = 25.8%), smoking persistence (random effect model (REM): OR = 0.85, 95%CI: 0.59-1.23, I(2) = 66.3%) and smoking cessation (REM: OR = 0.89, 95%CI: 0.57-1.40, I(2) = 67.1%). But it showed a significant protective effect of CYP2A6*4 on smoking initiation (FEM: OR = 0.78, 95%CI: 0.61-0.99, I(2) = 28.2%), smoking persistence (FEM: OR = 0.53, 95%CI: 0.36-0.77, I(2) = 41.0%) and smoking cessation (REM: OR = 0.49, 95%CI: 0.31-0.80, I(2) = 0.0%).

CONCLUSIONSThis Meta-analysis suggested that there was not a protective effect of defective CYP2A6 gene against smoking behaviors. But smokers with whole CYP2A6 gene deletion would be less likely to start smoking, less smoking persistence and more likely to quit smoking successful than smokers with wild CYP2A6 gene.

Aryl Hydrocarbon Hydroxylases ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2A6 ; Gene Deletion ; Humans ; Polymorphism, Genetic ; Protective Factors ; Smoking ; Smoking Cessation ; Tobacco Use Disorder

OBJECTIVE: To compare the difference in intraocular pressure (IOP) readings as well as the tolerability between Icare rebound tonometer (Icare RBT) and Goldmann applanation tonometer (GAT), and to evaluate the application of Icare RBT in monitoring the intraocular pressure in children after congenital cataract surgery. METHODS: The IOP was measured with the Icare RBT and GAT respectively in 150 children (262 eyes) after congenital cataract surgery by two experienced ophthalmologists. Correlation and Bland-Altman analysis were used to assess the agreement in IOP readings between the two instruments. The influence of the central corneal thickness (CCT) adjusted for age on IOP readings was analyzed by linear regression analysis. The tolerance of the patients to Icare RBT and GAT measurement were surveyed. RESULTS: The mean age was (44.82 ± 11.56) months in 150 children, including 81 boys and 69 girls. The mean IOP readings by the Icare RBT and GAT were (16.08 ± 5.72) mmHg and (14.17 ± 5.05) mmHg, respectively. The mean difference between the Icare RBT and GAT was (1.91 ± 2.04) mmHg, which was significantly correlated with CCT (r=0.409, P<0.001). The IOP readings by Icare RBT was significantly correlated with that measured by GAT(r= 0.936, P<0.001). The 95% confidence interval of the difference between the two instruments was ?2.10 to 5.91 mmHg. The Icare RBT examination was well tolerated by the children compared to the GAT examination. CONCLUSION The Icare RBT is easy to use and well tolerated by the children after congenital cataract surgery. Compared to GAT, the value measured by the IOPs trends to be overestimated. The difference in readings between the 2 tonometers will magnify with the increase in CCT.
Cataract ; congenital ; Cataract Extraction ; Child, Preschool ; Female ; Humans ; Intraocular Pressure ; Male ; Tonometry, Ocular ; instrumentation

OBJECTIVETo study the association between reasons for smoking and results related to successful smoking cessation.

METHODSA community-based case-control study was conducted with 642 male adults recognized as successful spontaneous smoking quitters being the subject cases while another 700 male adults who had failed to quit smoking were served as the controls. Russell Reason for Smoking Questionnaire (RRSQ) was used to investigate the reasons for smoking. Dominance logistic regression was performed to determine the relative importance of reasons for starting smoking and the endpoint of successful quit smoking.

RESULTSAfter adjusting the potential confounders of age, age of smoking initiation, marital status, profession, and education, the adjusted means of sedative and stimulation of RRSQ in the successful quitters were significant lower than that in the failed quitters. Results from the dominance logistic regression showed that the first two important factors for smoking cessation were sedative and stimulation of RRSQ, followed by psychological image, automatic, hand-mouth activity, indulgence, and addiction.

CONCLUSIONThis study demonstrated that factors as dependence-addiction showed more important impacts than the social-psychological ones on the endpoint of successful smoking cessation.

Adult ; Behavior, Addictive ; Case-Control Studies ; Humans ; Male ; Smoking ; psychology ; Smoking Cessation ; statistics & numerical data ; Smoking Prevention ; Surveys and Questionnaires

Objective To study the association between reasons for smoking and results related to successful smoking cessation. Methods A community-based case-control study was conducted with 642 male adults recognized as successful spontaneous smoking quitters being the subject cases while another 700 male adults who had failed to quit smoking were served as the controls. Russell Reason for Smoking Questionnaire(RRSQ)was used to investigate the reasons for smoking. Dominance logistic regression was performed to determine the relative importance of reasons for starting smoking and the endpoint of successful quit smoking. Results After adjusting the potential confounders of age,age of smoking initiation,marital status,profession,and education,the adjusted means of sedative and stimulation of RRSQ in the successful quitters were significant lower than that in the failed quitters. Results from the dominance logistic regression showed that the first two important factors for smoking cessation were sedative and stimulation of RRSQ,followed by psychological image,automatic,hand-mouth activity,indulgence,and addiction. Conclusion This study demonstrated that factors as dependence-addiction showed more important impacts than the social-psychological ones on the endpoint of successful smoking cessation.

Objective Metabonomics method based gas chromatography-mass spectrometry (GC/MS)were used to analyze the urine samples of patients with hyperlipidemic pancreatitis (HLP) to describe the characteristics of metabolism changes of HLP,identify potential biomarkers,and investigate the role of metabonomics study in the management of AP.Methods 24 patients of HLP and 40 age,sex matched volunteers were enrolled and their urine samples were collected.The urine samples underwent preparation,derivation and GC/MS analysis,Orthogonal-Projection to Latent Structures-Discriminant Analysis (OPLS-DA)were performed to detect the metabolic profile difference between the HLP and control group.Results HLP patients can be precisely distinguished from healthy controls.21 metabolites (credibility ＞ 700 ) were identified using the reference compounds available in the libraries of NIST and Wiley.It was identified that levels of nicotinic acid,aconitie acid,citric acid,hippurie acid,hydroxyphenylacetic acid,hydroxyphenylpropionicacid were decreased,while the levels of tryptophan,tyrosine,tyramine,16-hexadecanoic acid,18octadecanoie acid were increased.It was also suggested that there was change in tricarboxylic acid cycle and gut bacterial flora,as well as fat metabolism and metabolism of amino acid.Conclusions There are differences between healthy controls and HLP patients in the term of GC/MS metabolic profiling,and the biomarkers in the metabolites could be found through metabonomics analysis,and the mechanisms of the metabolic changes could be explored.It was noted that the research of metabolites in the urine samples may be a useful tool to help diagnose and understand the pathogenesis of HLP.Metabonomics analysis is a promising research method.

Objective To explore the related factors with plasma neuropeptide Y in 180 normal healthy people by stepwise regression analysis. Methods Right ventricular end-diastolic diameter(RVDD),inter-ventricular septum end-diastolic thickness(IVST),left ventricular end-diastolic diameter(LVDD),left ventricular posterior wall end-diastolic thickness(LVPWT),ejection fraction(EF),strole volume(SV),cardiac output(CO),cadiac output index(CI),stroke volume index(SI) and plasma neuropeptide Y were measured respectively by echocardiography and immunoradioassay in all subjects. In addition,we examined the height,weight,blood pressure,heart rate and subcutaneous fat thickness in every subjects. Results The plasma neuropeptide Y wasn't significant difference in different gender and age(P≥0.05). The plasma neuropeptide Y of healthy population was normal distribution and the 95% of confidence interval 70.27 to 190.61,and 99% of confidence interval was 51.23 to 209.65. Conclusion The EF,height,LVST,diastolic blood pressure,CO,SV and subcutaneous fat thickness were the major related-factors of neuropeptide Y in plasma. The EF and height were negatively correlated with plasma neuropeptide Y,and other five factors were postive correlated with it.