Objective: To observe the impact of cardiac contractility modulation (CCM) on myocardial remodeling in rabbit model of chronic heart failure (CHF) with its possible mechanism. Methods: Rabbit HF model was established by ascending aortic root ligation; the animals were divided into 3 groups: Sham group, the animals received thoracotomy without aortic ligation, HF group and HF+CCM group, the HF animals received CCM treatment for 4 weeks. n=10 in each group. Cardiac function was measured by echocardiography at 12 and 16 weeks in each group respectively; myocardial tissue fibrosis and pathological changes were examined by Masson staining; plasma BNP level was assessed by ELISA; protein expressions of collagen I, collagen II, MMP2,MMP9, TIMP1 and galectin-3 in myocardial tissue were determined by Western blot analysis. Results: ① By echocardiography: with 12 weeks treatment, compared with Sham group, HF group and HF+CCM group had increased LVESD, LVEDD and decreased LVFS, LVEF, all P<0.05; with 16 weeks treatment, compared with HF group, HF+CCM group had improved LVESD, LVEDD, LVEF and LVFS, all P<0.05. ② Pathological changes:compared with Sham group, HF group showed increased collagen content in myocardial tissue, P<0.05; CCM treatment could partially decrease collagen accumulation, P<0.05. ③ After 12 weeks treatment, compared with Sham group, HF group and HF+CCM group presented elevated plasma BNP level, P<0.05; after 16 weeks treatment, compared with HF group, HF+CCM group presented reduced plasma BNP, while it was still higher than that in Sham group, P<0.05. ④ By Western blot analysis: compared with Sham group, HF group demonstrated increased protein expressions of collagen I, collagen II, MMP2, MMP9, TIMP1 and galectin-3 in myocardial tissue; the above indexes were much lower in HF+CCM group while still higher than those in Sham group, all P<0.05. Conclusion: CCM could improve myocardial remodeling in rabbit model of CHF which might be related to down-regulated protein expressions of collagen I, collagen III, MMP2, MMP9, TIMP1 and galectin3 in myocardial tissue.

Objective To study the effect of cardiac contractility modulation (CCM) on TGFβ1/Smad/CTGF signaling pathway.Methods A rabbit heart failure (HF) model was established by ligating the ascending aortic root.Thirty rabbits were divided into sham operation group (n=10),HF group (n=10) and CCM group (n=10).Myocardial tissue collagen Ⅰ and collagen Ⅲ were analyzed with Sirius red staining,myocardial tissue hydroxyproline level was measured by chromometry,and expressions of TGFβ1,Smad3,Smad7,CTGF were detected by Western blot in 3 groups.Results Collagen Ⅰ,collagen Ⅲ and hydroxyproline content were highcr in HF group than in sham operation group,while collagen Ⅰ,collagen Ⅲ and hydroxyproline conten were lower in CCM group than in sham operation group (0.69±0.05 μg/mg vs 0.98±0.04 μg/mg,P＜0.05).The expression levels of TGFβ1,Smad3,CTGF were higher while those of Smad7 were lower in HF group than in sham operation group (P＜0.05).The expression levels of TGFβ1,Smad3,CTGF were lower while those of Smad7 were higher in CCM group than in HF group (0.49±0.03 vs 0.67±0.04,0.43±0.06 vs 0.59±0.06,0.45±0.08 vs 0.75±0.09,P＜0.05;0.43±0.08vs 0.26±0.04,P＜0.05).Conclusion CCM can improve the myocardial fibrosis in HF rabbits by downregulating the expression of TGFβ1,Smad3,CTGF and upregulating the expression of Smad7.

Objective To explore dynamic changes of renal cortex blood perfusion in Goto-Kakizaki rats(GK rats) by contrast-enhanced ultrasonography.The clues for early diagnosis and intervention of diabetic renal impairment may be obtained from the study.Methods Male GK rats were taken as experimental groups,and Wistar male rats were used as controls.Contrast-enhanced agent SonoVue was administered via the femoral vein cannulation in a bolus fashion.Image changes of renal cortex were observed in real time, and dynamic image changes within 0 - 5 minute after injection were observed and stored.The renal cortex blood perfusion changes were analyzed using the time-intensity curve (TIC).Results (1) The kidney was quickly enhanced after the injection of contrast agent.The renal artery, cortex, renal vein were displayed in sequence.(2)The shape of renal perfusion TIC in all the objects was a single peak,steep ascending, flat descending curve.The overall shape of TIC in GK rats was wider than controls and they were wider and wider with age increasing of the GK rats.(3) Compare to controls,the time to peak (TTP)and the half time of peak descending (HDT) in GK rats was longer (P ＜0.01), the slope rates of the ascending curve (S1) and the slope rates of the descending curve (S2) decreased and the area under the curve increased in 12-week-old and 20-week-old GK rats (P ＜ 0.05 or P ＜ 0.01).Conclusions The abnormal blood perfusion of renal cortex microcirculation was present in the early stage of diabetic in GK rats.Real-time contrast-enhanced ultrasonography and TIC could display this change effectively.

OBJECTIVETo explore the effect of apigenin on semen parameters in male mice.

METHODSTotally 100 healthy male mice of Kunming strain were randomly divided into 5 groups according to the body weight: negative control, solvent control, low-dose apigenin, median-dose apigenin and high-dose apigenin, the latter three groups given intragastric apigenin at a fixed time every day for 7 and 14 days. At 35 days after the first medication, all the mice were killed and detected for the sperm motion parameters by computer aided sperm analysis (CASA).

RESULTSThere were no statistically significant differences in sperm motion parameters, density and motility between the negative control and the three apigenin groups after 7-day medication. At 14 days, the high-dose apigenin group showed remarkable decreases in average path velocity (VAP), straight line velocity (VSL), straightness (STR), wobbliness (WOB), the percentage of grade b sperm and sperm motility, and a significant increase in beat cross frequency (BCF) as compared with the negative control group (P < 0.05).

CONCLUSIONApigenin affects sperm motility in male mice to a certain extent.

Animals ; Apigenin ; pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Semen ; drug effects ; Sperm Motility ; drug effects

OBJECTIVETo explore the underlying mechanism of mesenchymal stem cells (MSCs) transfer induced cardiac function improvement in failing hearts.

METHODSCongestive heart failure (CHF) was induced in rats by cauterization of the heart wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 days after cauterization.

RESULTSTen weeks later, cardiomyocyte nucleus mitotic index, capillary density and expression of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) were significantly increased in the border zone and significantly reduced in the remote myocardium in CHF rats (all P<0.05 vs. sham). Besides cardiac function improvement and left ventricular remodeling attenuation evidenced by hemodynamic and echocardiographic examinations, expressions of IGF-1, HGF and VEGF in the remote myocardium and in the border zone were also significantly upregulated (P<0.05 or P<0.01 vs. CHF), and cardiomyocyte nucleus mitotic index as well as capillary density were significantly increased in CHF rats with MSCs (P<0.05 or P<0.01 vs. CHF). Moreover, collagen area was significantly reduced and myocardial area was significantly increased in the border zone in these rats too.

CONCLUSIONAutologous MSC implantation upregulated expressions of growth factors enhanced cardioangiogenesis which might be the underlying mechanisms for improved cardiac function and attenuated left ventricular remodeling induced by MSCs transplantation in failing rat myocardium.

Animals ; Disease Models, Animal ; Heart Failure ; metabolism ; therapy ; Hepatocyte Growth Factor ; metabolism ; Insulin-Like Growth Factor I ; metabolism ; Male ; Mesenchymal Stem Cell Transplantation ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transplantation, Autologous ; Vascular Endothelial Growth Factor A ; metabolism ; Ventricular Remodeling

OBJECTIVETo analyze the frequency of beta-fibrinogen (beta-Fg) gene -455G/A, -148C/T and 448G/A polymorphism, fibrinogen molecular reactivity and their association with plasma fibrinogen levels in health adults, myocardial infarction and cerebral infarction disease.

METHODSThe beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms were analyzed by restriction fragment length polymorphism (RFLP). Fibrinogen molecular reactivity was analyzed for the conversion kinetics of fibrinogen into fibrin by a computer assistant procedure. Plasma fibrinogen levels were determined by Clauss method.

RESULTSThe frequencies of -455A, -148T, 448A allele in health adults were 0.185, 0.194 and 0.192, in myocardial infarction disease 0.295, 0.318 and 0.307, in cerebral infarction disease 0.177, 0.193 and 0.182, respectively. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. There were close linkage between -455G, -148C and 448G or -455A, -148T and 448A, the correspondence was over 98%. There are no differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level.

CONCLUSIONThe three polymorphisms loci are strong linkage disequilibrium. There are no significant differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. It suggest that there was no association between beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms and plasma fibrinogen levels, but did in myocardial infarction disease. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level.

Adult ; Aged ; Aged, 80 and over ; Caenorhabditis elegans Proteins ; Cerebral Infarction ; genetics ; Female ; Fibrinogen ; analysis ; Gene Frequency ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Muscle Proteins ; genetics ; Myocardial Infarction ; genetics ; Polymorphism, Genetic

OBJECTIVETo investigate the recent emerged endemic region of tick-borne encephalitis (TBE) regarding its natural reserves, in Charles Hilary, northern Xinjiang and to isolate and characterize the viral geographic strain.

METHODSUsing indirect fluorescent assay to detect tick-borne encephalitis virus (TBEV) specific IgG antibodies from serum of local residents including 2 unconfirmed viral encephalitis patients in 2011 spring-summer. Viruses were isolated from tick samples by inoculating BALB/c mice and BHK-21 cells. For phylogenetic analysis. TBEV NS1 gene fragments were detected by RT-PCR and then subjected to sequence alignment.

RESULTS1760 ticks were captured from the fields to have found that Ixodes persulcatus were dominated among the tick population. Two viral encephalitis patients were diagnosed as TBEV infection. In addition, 35.4% (23/65) local residents were detected positive for presence of TBEV specific-IgG antibodies in serum. After inoculation, morbidity and mortality of BALB/c mice were 72.9% (70/96) and 55.7% (44/79), respectively. TBEV specific-fragments were amplified from brain tissue of dead mice and cells culture supernatant. NS1 sequence alignment showed that the viral isolates were clustered into TBEV far-eastern sub-type, phylogenetically, and were mostly close to the isolates from northeastern China (99%) and Russian strain (98%).

CONCLUSIONIn this study, a new endemic loci of TBE was firstly described in Charles Hilary natural reserve, northern Xinjiang. TBEV geographic isolates belonged to TBEV far-eastern subtype while Ixodes persulcatus and Dermacentor silvarum played crucial roles for disease transition.

Adult ; Animals ; China ; epidemiology ; Encephalitis Viruses, Tick-Borne ; genetics ; immunology ; isolation & purification ; Encephalitis, Tick-Borne ; epidemiology ; transmission ; virology ; Female ; Humans ; Male ; Mice ; RNA, Viral ; genetics

OBJECTIVETo explore the effects of hepatitis B virus X protein (HBx) on hepatoma cell growth through p14(ARF)-dependent and p14(ARF)-independent pathways.

METHODSHBx and p14(ARF) were transfected either separately or in combination into HepG2 cells containing wt-p53 but not expressing p14(ARF). The cells were divided into 4 groups, namely pcDNA3 (control), pcDNA3HBx, pcDNA3p14(ARF), and pcDNA3HBx + pcDNA3p14(ARF) groups. Flow cytometry was used to examine the apoptosis rates and cell cycle progression of HepG2 cells in different groups. The expression of p14(ARF), MDM2, p53, and p21(WAF1) proteins were investigated by detecting the activity of p21(WAF1) promoter-luciferase and using Western blotting.

RESULTSThe apoptosis rates of HepG2 cells in pcDNA3HBx and pcDNA3p14(ARF) groups were significantly higher than that in the control group (14.11%, 13.72% vs 10.66%). Compared with the control group, pcDNA3HBx and pcDNA3p14(ARF) groups also showed significantly higher cell percentages arrested at G(0)/G(1) phase (63.62%, 61.75% vs 57.42%), luciferase activity of p21 promoter (1.25-/+0.05, 1.09-/+0.06 vs 0.77-/+0.03) and expressions of p53 and p21(WAF1). The cell apoptosis rate, percentage of cells in G(0)/G(1) phase and expression level of p14(ARF) were even higher in pcDNA3HBx+pcDNA3p14(ARF) group (18.61%, 66.74%, and 3.53-/+0.43, respectively) than in either p14(ARF) or HBx group.

CONCLUSIONHBx induces p53 expression through p14(ARF)-dependent and independent pathways to activate p21(WAF1) promoter, leading to G(0)/G(1) arrest and apoptosis of HepG2 cells.

Carcinoma, Hepatocellular ; genetics ; pathology ; virology ; Cell Line, Tumor ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; Humans ; Liver Neoplasms ; genetics ; pathology ; virology ; Promoter Regions, Genetic ; Trans-Activators ; genetics ; Transfection ; Tumor Suppressor Protein p14ARF ; genetics ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo establish a method of the quantitative determination of acetylharpagide in Ajuga decumbens.

METHODThe chromatographic conditions were as follows: a Phenomenex Luna C18 column was used, the mobile phase was composed of acetontrile-water (15:85), the flow rate was 1.0 mL x min(-1) and the UV absorbance detection was set at 197 nm.

RESULTLinearity of acetylharpagide was in the range of 0.6-3.6 microg (r = 0.9993), and the average recovery and RSD were 99.13% and 2.48%, respectively.

CONCLUSIONThe contents of acetylharpagide ranged 0.40%-6.39% in A. decumbens. The method was simple, accurate and sensitive.

Ajuga ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Plants, Medicinal ; chemistry ; Pyrans ; analysis ; Reproducibility of Results ; Sensitivity and Specificity

Objective To evaluate the clinical efficacy of endoscopic transnasal palatal nerve block for persistent allergic rhinitis.Methods 123 patients with heavy persistent allergic rhinitis who aged over 17 years old in Longhua central hospital affiliated to Guangdong medical university from October 2013 to February 2015 were divided into observation group and control group.The patients in the observation group(72 cases) were blocked with endoscopic sphenopalatine,the control group (51 cases) treated with medicine.The rhinoconjunctivitis quality of life questionnaire (RQLQ) and VAS were assessed before and after treatment for 6 months,1 year and 2 year survival.Results 106 patients were followed up for 2 years.In observation group,the average score of RQLQ and VAS before treatment were (2.39 ± 0.43),(7.45 ±1.24) respectively;6 months after treatment,the average scores of RQLQ and VAS were (0.82 ± 0.38),(2.47 ± 1.42) respectively;1 years (0.93 ± 0.41) and (2.53 ± 1.54);2 years (1.05 ± 0.47) and (2.67 ± 1.69);the differences were statistically significant (P ＜ 0.05).The control group showed no obvious difference in RQLQ and VAS before and after treatment.Conclusion Endoscopic sphenopalatine nerve block can effectively improve the quality of life of patients with persistent rhinitis allergic,which is safe and effective in the treatment of severe persistent allergic rhinitis.