Objective To explore the changes in expression levels of nuclear factor(NF)-κB,tumor necrosis factor(TNF)-e in the lungs of juvenile mice with acute lung injury(ALI) induced by lipopolysaccharide(LPS).And observe the repair of lung damage after intervening with exogenous mesenchymal stem cells(MSCs).Methods Thirty male juvenile C57 mice were randomly divided into the control group,the ALI group,and the ALI + MSCs group by the random number table method.Mice from each group were euthanized at 12 h and 48 h.The ALI model of juvenile mice was established by intraperitoneal injection of LPS 10 mg/kg.MSCs from mice bone marrow were isolated,cultured and amplified in vitro,and the MSCs (1 × 106/ml) 0.1 ml were given to mice via caudal vein.MSCs marker were identificated by flow cytometry.Pathomorphological changes of mice lung were observed under light microscope after Hematoxylin-Eosin staining.The protein expression changes of NF-κB,TNF-α were observed using immunohistochemistry.Resu]ts Compared with the control group,the protein expression levels of NF-κB,TNF-α were significantly higher at 12 h and 48 h in the lungs of the ALI group(P ＜ 0.05).While those in ALI + MSCs group were markedly lower at these time points than the ALI group [NF-κB:12 h:(0.181 ± 0.008) OD vs (0.203 ±0.008) OD,48 h:(0.197 ± 0.002) OD vs (0.210 ± 0.005) OD; TNF-α:12 h:(0.185 ± 0.004) OD vs (0.201 ± 0.011) OD,48 h:(0.185 ± 0.002) OD vs (0.215 ± 0.009) OD] (P ＜ 0.05).Histopathological evalution showed that typical pathological inflammation lesions in the lung were observed in ALI group,including alveolar congestion,hemorrhage,edema,infiltration of neutrophils in the airspace or vessel wall,thickness of the alveolar wall;pathological changes were relieved obviously in ALI + MSCs group.Conclusion The expression of NF-κB and TNF-α are increased in lung tissues in the juvenile mice model of ALI induced by LPS.MSCs can alleviate injury degree of ALI induced by LPS in mice,the mechanism of action may correlate with decreasing NF-κB and TNF-α content in lung tissue.

Objective To evaluate the effect of percutaneous coronary intervention (PCI) on left ventricular function in patients with different types of myocardial infarction and to explore the correlation factors for the left ventricular function.Methods A total of 43 patients diagnosed as acute myocardial iffarction were enrolled in this study.The perfusion and delayed enhancement magnetic resonance imaging (DE-MRI) was applied to observe the following parameters before the PCI and at month 6 after the procedure:infarct mass,left ventricular ejection fraction (LVEF) and abnormal wall motion score.The subjects were divided into the following three groups by the transmural extent of myocardial infarction manifested in the DE-MRI:the transmural enhancement group,the nontransmural group and the mixed group.Laboratory test was done to detect the level of endothelin (ET),matrix metal enzyme 9 (MMP-9) and high sensitive C reactive protein (hsCRP) before PCI and at month 6 after the procedure.The t test was used to compare the differences among the groups and the multiple regression analysis was taken to explore the correlation factors for the left ventricular function.Results Compared with the parameters before PCI,the infarct mass after PCI significantly decreased in the nontransmural group and the mixed group [(4.0 ± 2.9) g/cm3 vs (9.8 ±5.6) g/cm3 and (6.0 ±3.5) g/cm3 vs (11.8 ±6.2) g/cm3,all P ＜0.05],while LVEF was significantly improved after PCI in both groups [(52.6 ± 15.4) ％ vs (41.9 ± 16.3) ％,(45.6 ± 15.4)％ vs (38.9 ± 16.3)％,all P ＜0.05].The infarct mass was an independent correlation factor for LVEF before PCI (RR =0.318,P ＜0.05) and LVEF after PCI(RR =0.293,P ＜0.05).LVEF before PCI was independently correlated with the level of hsCRP (RR =0.318,P ＜ 0.05).Conclusion The effect of PCI on the improvement of left ventricular function differs in patients with different extent of myocardial infarction,which is correlated with the amount of survival myocardium and the inflammatory factors.

Objective To study the changes of reactive astrocytosis after heat shock protein 70 (HSPT0) was blocked by anti-HSP70 antibody. Methods We established cell model of scratch inju-ries by in situ culture and prurification of rat astrocytcs. Anti-HSP70 antibody was added into the nutrient medium at once after injury for intervention (intervention group). Then, immunocytochemical staining of glial fibrillary acidic protein (GFAP) was done at different time points in control group and intervention group to observe astrocytosis and morphologic changes, mRNA expression of GFAP was observed by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Results Compared with the con-trol group, average cell area, average dentritic length and number of dentrities of astrocytes were signifi-cantly reduced in the intervention group(P < 0.05 or P < 0.01), with down-regulated mRNA expression of GFAP (P < 0.05). Conclusion HSP70 plays a facilitative role in reactive astrocytosis after injury of astrocytes. Reactive astrocytosis can be controlled to some extent by blocking HSP70 with anti-HSP70 antibody.

Objective To evaluate the serum 25-hydroxyvitamin D [25 (OH)D3] levels in non-diabetic people in Taiyuan community,and its relationship with obesity and abdominal obesity.Methods This crosssectional study enrolled 417 non-diabetic people in Tainyuan community from July to September in 2011 [225 males and 192 females,mean age (47.6 ±7.8) years].For all the enrolled subjects,we collected data about anthropometric indexes,medical history,blood glucose,lipid profile,25 (OH) D3,fasting insulin (Fins) level,homeostasis model assessement for insulin resistance (HOMA-IR),body fat content (％) measured with dualenergy X-ray absorptiometry (DEXA),and intra-abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (SCAT) calculated based on magnetic resonance imaging at the 4th to 5th lumbar disc level (IAAT≥80 cm2 was considered abdominal obesity).Correlation analysis was performed to assess the relationships of serum 25 (OH) D3 levels with biochemical and body fat indexes.Results The average serum level of 25 (OH) D3 was 44.5 nmol/L in the 417 people,with vitamin D deficiency in 261 cases (62.6％) and vitamin D insufficiency in 109 cases (26.1％).Of the vitamin D deficient and insufficient people,77.6％ had abdominal obesity according to IAAT (IAAT ≥ 80 cm2).According to Pearson analysis result,lg 25 (OH)D3 was negatively correlated with lg Fins,lg HOMA-IR,waist circumference,systolic blood pressure,diastolic blood pressure,total abdominal adipose tissue (TAAT),IAAT (all P ＜0.05).It was also negatively correlated with waist-to-hip-ratio,body mass index (BMI),and body fat content (％),but without statistical significance (all P ＞0.05).In stepwise multiple linear regression model,lg HOMA-IR (t =-4.278,P =0.001) and TAAT (t =-5.146,P =0.002) were independently correlated with lg 25 (OH) D3.Conclusions About 90％ of all non-diabetic population in Taiyuan community have vitamin D deficiency or insufficiency,of whom 4/5 have abdominal obesity.Serum 25 (OH)D3 level is negatively correlated with abdominal adipose tissue,but not significantly associated with BMI.HOMA-IR and TAAT are independent risk factors for vitamin D deficiency.

Objective To analyze the overall developmental stages of traditional Chinese materia medica patent technology in China and abroad and the causes of the differences. Methods In this study, the Shanghai Intellectual Property Information Platform, Thomson Innovation, Derwent Innovations Index were utilized and graphic illustration method for patent technology life cycles was used to determine the overall developmental stages of traditional Chinese materia medica patent technology in China and abroad. Results The numbers of applications for patent traditional Chinese materia medica and their applicants were obtained. With information of the two parameters, the text made a preliminary prediction of overall trend for the number of applications. Conclusion The patent technology of traditional Chinese materia medica progressed into developing stages in China and appeared the feature of mature or recession stage abroad.

OBJECTIVE:To systematically review the effect of organic cation transporter 2 [(OCT2)808G>T] gene polymor-phism on the metformin hydrochloride pharmacokinetics in vivo,and to provide evidence-based reference for clinical medication. METHODS:Retrieved from PubMed,EMBase,Foreign Medical Journey Service,CJFD,VIP database and Wanfang database,re-lated studies about the effect of (OCT2)808G>T gene polymorphism on the metformin hydrochloride pharmacokinetics in vivo were collected,and Meta-analysis was performed by using Rev Man 5.1 statistics software. RESULTS:A total of 5 retrospective studies were included,involving 172 patients. The result of gene type was type GT,type TT and type GG. Results of Meta-analysis showed,compared with type GT volunteers,type TT could prolong the half-time period of metformin hydrochloride;compared with type TT,type GG could increase the peak concentration. However,(OCT2)808G>T gene polymorphism had no effects on the renal clearance rate,creatinine clearance rate and area under the drug-time curve. CONCLUSIONS:(OCT2)808G>T gene poly-morphism has certain effect on the half-time period and peak concentration of metformin hydrochloride in vivo of health volunteer, and has no effect on the renal clearance rate,creatinine clearance rate and area under the drug-time curve. Due to the limit of re-search methodological quality,large-scale and high quality studies are required for further validation of the conclusions.

Pim kinases contribute to tumor formation and development of lymphoma, which shows enhanced DNA replication, DNA recombination and repair. Endothelial cells^(ECs) express all the three members of Pim kinase gene family. We hypothesized that DNA repair gene would regulate Pim expression in ECs. Human umbilical vein endothelial cells (HUVECs) were isolated and maintained in M199 culture medium. The cellular distribution of Pim-3 in ECs was determined by immunofluorescent staining. The siRNA fragments were synthesized and transfected by using Lipofectamine LTX. The total cellular RNA was extracted from the cells by using Trizol reagent. cDNAs were quantified by semi-quantity PCR. The effects of LY294002 and wortmannin on RNA stability in ECs were also examined. Our data showed that LY294002 and wortmannin, phosphatidylinositol 3-kinase (PI3K) and PI3K-like kinase inhibitors, increased Pim mRNA expression in ECs without altering the mRNA stability. RNA interference (RNAi) targeting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) increased mRNA expression of Pim-3 and Pim-1, respectively. Silencing of Akt decreased Pim-1 instead of Pm-2 and Pim-3 gene expression in ECs. But etoposide, a nucleoside analogue, which could activate DNA-PKcs and ATM, increased Pim expression in ECs. Our study indicates that the expression of Pim kinases is physiologically related to DNA-PKcs and ATM in ECs.

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
Animals ; Anti-Arrhythmia Agents ; administration & dosage ; Antibiotics, Antineoplastic ; Carbazoles ; administration & dosage ; Cardiomyopathies ; chemically induced ; physiopathology ; prevention & control ; Doxorubicin ; Heart Rate ; drug effects ; Male ; Metoprolol ; administration & dosage ; Oxidative Stress ; drug effects ; Propanolamines ; administration & dosage ; Rabbits ; Treatment Outcome ; Ventricular Fibrillation ; chemically induced ; physiopathology ; prevention & control

Intracellular Ca2+ and Ca2+-dependent signaling molecule play an essential role in the genesis of long-QT (LQT) syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential (MAP) recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode's solution. Bradycardia was induced by com-plete ablation of atrioventrtcular node. A catheter was introduced into the right ventricle to pace at the cycle lengths (CLs) of 1500, 1000, and 500 ms, successively. Quinidine (2 μol/L) prolonged QT in-terval and ventricular MAP duration (MAPD), and increased transmural dispersion of repolarization (TDR) in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil (0.01-0.05 μmol/L) used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syn- drome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.