AIM: The study was undertaken to explore the dynamic changes of the concentration of nitric oxide(NO) in ischemic myocardium and its mechanism.METHODS: In vivo myocardial ischemia of mice and in vitro perfused isolated heart of rat were used in the experiment. The effects of severity and time of ischemia on NO production, NOS activity and mRNA were examined, respectively. RESULTS: There was a considerable difference (P

Objective To develop miniature pig model of coronary microembolization (CME) by easy and cost-effi-cient technique. Methods A total of 11 miniature pigs were divided into control group (n=5) and CME group (n=6). Femo-ral artery was punctured using 21 gauge needle that is normally used for transradial procedures. Microspheres were injected into the left anterior descending artery of the CME group by 5 F coronary radiography catheter and 1.8 F coronary micro-guide catheter. Serum concentrations of brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) were evaluated just be-fore CME and 6 hours after CME. Apical myocardial pathological lesions were evaluated by optical microscope 6 hours after CME. Results All miniature pigs in control group survived, but one died in the CME group. 5 F coronary radiography cathe-ter and 1.8 F coronary micro-guide catheter reached designated location successfully. Before CME, serum BNP (ng/L:143.00 ± 13.51 vs 134.00 ± 15.57) and cTnI (μg/L:0.39 ± 0.09 vs 0.38 ± 0.10) showed no significant differences between these two groups (t values are 0.976 and 0.294 respectively,both P>0.05). By contrast, serum BNP (561.00 ± 80.65) and cTnI (2.75±0.58) were much higher in CME group than those (BNP 139.00±13.87;cTnI 0.54±0.14 ) in control group after CME (t values are 11.530 and 8.337 respectively,both P＜0.001). In CME group, microspheres, micro-infarction and inflammatory cell infiltration were seen under an optical microscope which are absent in control group. Conclusion Using new surgical consumables can successfully develop miniature pig model with CME. And the technique is simple, cost-efficient, practical so it is worth promoting.

0.05). Conclusion Tianma Gouteng Decoction can reverse left ventricular hypertrophy and myocardial fibrosis,and its mechanism may be related to the inhibition of TGF-? 1 expression in cardiac muscle tissue.

Aim To investigate the roles of mitogen-ac-tivated protein kinases ( MAPK ) pathways in the pro-tective effects of remifentanil preconditioning against is-chemia/reperfusion injury of isolated heart in rats with heart failure. Methods Adult male SD rats were injected with adriamycin via tail vein for 6 weeks to induce heart failure. The rats were confirmed chronic heart failure through echocardiography and randomly divided into 9 groups(n=6)as follows: sham group, ischemia/reperfusion group ( IR) , remifentanil precon-ditioning group( RPC) , ERK inhibitor PD98059+RPC group ( RPD ) , p38 inhibitor SB203580 +RPC group ( RSB ) , JNK inhibitor SP600125 + RPC group ( RSP ) , and the inhibitor control groups ( PD , SB and SP) . All hearts were linked to the Langendorff ap-paratus. The coronary effluent was collected to detect the activity of lactate dehydrogenase ( LDH ) at base-line, 5 min and 10 min after reperfusion, respectively. Infarct size ( IS) and area at risk ( AAR) were deter-mined by 2, 3, 5-triphenyl-tetrazolium (TTC) staining at the end of reperfusion. Left ventricular developed pressure ( LVDP), ± dp/dtmax and heart rate ( HR) were recorded to evaluate cardiac function in each group. Results When compared with IR group, RPC significantly reduced IS / AAR and decreased the ac-tivity of LDH at 5 min and 10 min after reperfusion. However, SP600125 almost thoroughly abolished the protective effects of RPC, as evidenced by the in-creased value of IS / AAR and the high activity of LDH. In addition, PD98059 also partly blocked the effects of RPC, while SB203580 showed no influence on RPC. Meanwhile, the hemodynamic parameters such as LVDP, HR and ± dp/dtmax were not signifi-cantly different in any group except sham group. Con-clusion JNK and ERK pathways may play an impor-tant role in cardioprotective effects of remifentanil pre-conditioning against ischemia/reperfusion injury in rats with heart failure.

Objective To explore the bioactive constituents of Gentiana rhodantha for its serum pharmacochemistry research.Methods The blood migrating constituents of Gentiana rhodantha were determined by comparing the HPLC fingerprints of the aqueous extracts,drug contained serum and blank serum.Results Twenty compounds were detected in drug contained serum,four among which were original constituents of Gentiana rhodantha,the rest might be metabolites of the original ingredients.Conclusion These twenty constituents absorbed in blood could be the bioactive components of Gentiana rhodantha.Further studies will be useful to clarify the bioactive constituents and action mechanisms of Gentiana rhodantha.

Objective To evaluate the roles of 1-phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) signaling pathways in reduction of ischemia-reperfusion (I/R) injury to the isolated hearts by morphine preconditioning in the rats with chronic heart failure.Methods Adult male Sprague-Dawley rats,weighing 200-230 g,in which doxorubicin 2.0 mg/kg was injected via the tail vein once a week for 6 weeks to induce chronic heart failure,were studied.At the end of 8th week,42 rats with chronic heart failure were randomly divided into 7 groups (n =6 each) using a random number table:sham operation group (group S),I/R group,morphine preconditioning group (group MP),PD98059 (ERK inhibitor) + morphine preconditioning group (group PD + MP),wortmannin (PI3K inhibitor) + morphine preconditioning group (group WT + MP),PD98059 group (group PD) and wortmannin group (group WT).The hearts were quickly excised and passively perfused in a Langendorff apparatus and subjected to 30 min of occlusion of the left coronary artery followed by 2 h of reperfusion to establish the model of I/R injury.In group S,the hearts were only sutured,but not ligated and were continuously perfused with K-H solution for 195 min.In group I/R,the hearts were perfused with K-H solution for 45 min before ischemia.In group MP,the hearts were perfused with K-H solution for 15 min,with K-H solution containing morphine 1 μmol/L for 5 min and then with K-H solution for 5 min (3 cycles in total) before ischemia.In PD + MP and WT + MP groups,the hearts were perfused with K-H solution containing PD98059 (10 μmol/L) and wortmannin (100 nmol/L),respectively,starting from 10 min before morphine preconditioning until 5 min of ischemia.In PD and WT groups,the hearts were perfused with K-H solution containing PD98059 (10 μmol/L) and wortmannin (100 nmol/L),respectively,starting from 40 min before ischemia until 5 rin of ischemia.At 15 min of equilibration (baseline) and 5 and 10 min of reperfusion,the coronary flow was collected to detect the activity of lactate dehydrogenase (LDH).Infarct size (IS) and area at risk (AAR) were measured at the end of reperfusion and IS/AAR ratio was calculated.Results Compared with group S,LDH activity was significantly increased at 5 and 10 min of reperfusion,IS and IS/AAR ratio were also increased (P ＜ 0.05),and no significant change was found in AAR in group I/R (P ＞ 0.05).Compared with group I/R,LDH activity was significantly decreased at 5 min of reperfusion,IS and IS/AAR ratio were also decreased (P ＜ 0.05),and no significant change was found in AAR in group MP,and no significant change was found in LDH activity,IS,AAR and IS/AAR ratio in WT and PD groups (P ＞ 0.05).Compared with group MP,LDH activity was significantly increased at 5 and 10 min of reperfusion (P ＜ 0.05),and IS and IS/AAR ratio were decreased in group PD + MP,and no significant change was found in LDH activity,IS,AAR and IS/AAR ratio in group WT + MP (P ＞ 0.05).Conclusion Activation of ERK signaling pathway is involved in reduction of I/R injury to isolated hearts by morphine preconditioning in rats with chronic heart failure,however,PI3K signaling pathway has no such effect.

Objective To evaluate the role of opioid receptors and phosphatidylinositol 3-kinase/proteinserine-threonine kinases (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathways in reduction of hypoxia/reoxygenation (H/R)-induced injury to cardiomyocytes by remifentanil preconditioning in rats.Methods Primary cardiomyocytes were obtained from adult male Sprague-Dawley rats and cultured in DMEM culture medium.The cells were seeded in 48-well plates (density 2 × 104 cells/ml,500 μl/well) and randomly divided into 12 groups (n =9 each):control group (group C),group H/R,hypoxia preconditioning group (group HPC),remifentanil preconditioning (RPC) group,naltrindole (δ receptor antagonist) + RPC group,nor-binaltorphimine (κ receptor antagonist) + RPC group (BNI + RPC group),wortmannin (PI3K inhibitor) + RPC group (W+ RPC group),PD98059 (ERK inhibitor) + RPC group (PD + RPC group),NTD group,BNI group,W group and PD group.In group H/R,the cardiomyocytes were exposed to 90 min of hypoxia,followed by 120 min of reoxygenation.In group HPC,the cardiomyocytes were exposed to 10 min of hypoxia,followed by 30 min of reoxygenation before H/R.In group RPC,the cardiomyocytes were preconditioned with remifentanil with the final concentration of 1 μmol/L for 10 min,followed by 30 min routine culture before H/R.In NTD + RPC,BNI + RPC,W + RPC and PD + RPC groups,naltrindole 5μmol/L (final concentration),nor-binaltorphimine 5 μmol/L (final concentration),wortmannin 0.1 μmol/L (final concentration) and PD98059 30μmol/L (final concentration)were added,respectively,and then the cells were coincubated with remifentanil for 10 min,followed by 30 min routine culture before H/R.The viability of cardiomyocytes,cell apoptosis and activity of lactate dehydrogenase (LDH) in the culture medium were detected.The apoptosis rate (AR) was calculated.Results Compared with group C,the viability of cardiomyocytes,AR and activity of LDH in the culture medium were significantly increased in group H/R (P ＜ 0.05).Compared with group H/R,the viability of cardiomyocytes,AR and activity of LDH in the culture medium were significantly decreased in HPC,RPC and BNI + RPC groups (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in NTD + RPC,W + RPC,PD + RPC,NTD,BNI,W,and PD groups (P ＞ 0.05).The viability of cardiomyocytes was significantly lower,and the AR and activity of LDH in the culture medium were higher in NTD + RPC,BNI + RPC,W + RPC,and PD + RPC groups than in RPC group (P ＜ 0.05).Conclusion Remifentanil preconditioning activates PI3K/Akt and ERK signaling pathways possibly through activating δ opioid receptors thus attenuating H/R-induced injury to cardiomyocytes in rats.

Objective To evaluate the effects of morphine preconditioning on the expression of microRNAs (miRNAs) during hypoxia-reoxygenation (H/R) in isolated cardiomyocytes in rats with heart failure.Methods Healthy adult male Sprague Dawley rats,w eighing 200-220 g,were used in this study.Adriamycin 2.0 mg/kg was injected once a week for 6 weeks via the tail vein to induce heart failure.The cardiomyocytes were isolated from the failing hearts of rats and seeded in 24-well plates or in 60 mm diameter dishes.The cells were then randomly divided into 3 groups (n =16 each) using a random number table:control group (group C); group H/R;morphine preconditioning group (group MP).The cells were cultured in normal culture atmosphere in group C.After being exposed to hypoxic air (5％ CO2-95％ N2) for 90 min,the cells were returned to the high-glucose DMEM supplemented with 10％ newborn bovine serum and were then cultured for 120 min in H/R and MP groups.In group M,the cells were cultured in morphine culture medium (final concentration of morphine 0.3 μmol/L) for 10 min and then were returned to the culture medium without morphine and cultured for 30 min immediately before hypoxia.At 120 min of reoxygenation,the cells of 8 wells in each group were chosen to detect the cell viability and lactate dehydrogenase (LDH) activity (by Typan blue staining).All the RNAs were extracted from the cardiomyocytes of the left 8 wells in each group and subjected to miRNA microarray to screen differentially expressed miRNAs.Results The cell viability was significantly lower,the activity of LDH was higher,the expression of miR-6216 and let7e-5p was higher,and the expression of miR-133b-5p was lower in H/R and MP groups than in group C (P ＜ 0.05).Compared with H/R group,the cell viability was significantly increased,the activity of LDH was decreased,the expression of miR-133b-5p was up-regulated,and the expression of miR-6216 and let-7e-5p was down-regulated in MP group (P ＜ 0.05).Conclusion Morphine preconditioning reduces H/R injury to isolated cardiomyocytes in rats with heart failure through regulating the expression of miRNAs such as miR133b-5p,miR-6216 and let-7e-5p.

Objective To investigate the risk factors of electrocoagulation syndrome after endoscopic submucosal dissection (ESD) in patients with colorectal lesions.Methods Clinical data of 145 patients with colorectal mucosal lesions undergoing ESD in People's Hospital of Wuhan University between September 2010 and September 2015 were retrospectively studied.Results Among 45 patients,post endoscopic submucosal dissection electrocoagulation syndrome (PEECS) was developed in 32 cases (22％).The median age in PEECS group was higher (t =-5.783,P =0.000),the median lesion size was larger(t =-5.590,P =0.000),the median length of hospital stay was longer (t =-6.841,P =0.000) than those in non-PEECS group.Univariate regression analysis showed PEECS was associated with the age,lesion size,lesion location,length of hospital stay,malignant tumor,polyps type,resection modality.Multivariable logistic regression analysis showed that the independent risk factors for the development of electrocoagulation syndrome were age ＞65 year (OR =1.123,95％ CI:1.013-1.244,P =0.027),lesion size ＞ 3.5 cm (OR =1.173,95％ CI:1.015-1.357,P =0.031),malignant tumor (OR =3.498,95 ％ CI:1.460-8.379,P =0.005),hospital stay ＞ 10 d (OR =2.480,95％ CI:1.346-4.569,P =0.004),non-rectal lesions (OR =12.612,95％ CI:3.446-46.157,P =0.000).Conclusion Attention should be paid for colorectal lesion patients with high risk of PEECS,when endoscopic submucosal dissection is performed.

An analysis of the opportunities and challenges brought forth to research hospitals in the face of emerging new technologies,described the development direction of such hospitals in terms of strategic planning of precision medicine, breakthrough of mechanism barriers for technology development,andInternet+ service mode innovation.These efforts aim at exploring to build a new type of medical technology service system.