OBJECTIVE: To investigate the effect of miR-133b on cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion (I/R) and explore the mechanism. METHODS: Thirty-six adult SD rats were randomized into sham-operated group, I/R group, AdmiR-NC group and AdmiR-133b group, and rat models of myocardial I/R were established in the latter 3 groups with myocardial injections of saline or recombinant adenoviruses in the left ventricle. The expression of MiR-133b was detected using RT-qPCR, and cardiac function of the rats was determined using FDP 1 HRV and BRS analysis system. Serum CK-MB and cTnI levels were determined by ELISA, myocardial injury was evaluated with HE staining, cardiomocyte apoptosis was detected by flow cytometry, and ROS content was determined using a DCFH-DA probe. In the in vitro experiment, H9C2 myocardial cells with hypoxia/reoxygenation (H/R) treatment were transfected with Mir-NC or MiR-133b mimic, and the cellular expression of MiR-133b, cell apoptosis, and ROS content were determined. Dual luciferase reporter assay was performed to verify the targeting relationship between miR-133b and YES1. The effects of pc-YES1 or miR-133b mimic transfection on YES1 expression, apoptosis, and ROS content in H9C2 cells were evaluated. RESULTS: Compared with those in I/R group, miR-133b expression was obviously up-regulated, LVEDP, cTnI and CK-MB levels were significantly decreased, and LVSP, +dp/dt, -dp/dt, HR and CF levels were increased in admiR-133b group ( CONCLUSIONS miR-133b can inhibit I/R-induced myocardial cell apoptosis and ROS accumulation by targeting YES1 to reduce myocardial I/R injury in rats.
Animals ; Apoptosis ; MicroRNAs/genetics* ; Myocardial Reperfusion Injury ; Myocytes, Cardiac ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species

Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%（44/57） vs. 41.4%（12/29），χ2=10.853， P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.

Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%（44/57） vs. 41.4%（12/29），χ2=10.853， P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.

Objective:To explore clinical significance of sinus heart rate turbulence (HRT) phenomenon in aged pa‐tients with stable angina pectoris (SAP) .Methods :A total of 120 aged SAP patients ,who received 24h DCG in our hospital from Jan 2013 to Oct 2015 ,were selected as SAP group .Meanwhile ,another 144 aged patients ,who re‐ceived 24h DCG examination simultaneously and coronary angiography results were normal ,were regarded as nor‐mal control group .According to coronary lesion severity ,SAP group was further divided into single vessel coronary disease group (single vessel group ,n=35) ,double‐vessel coronary disease group (double‐vessel group ,n=48) and multi‐vessel coronary disease group (multi‐vessel group ,n=37) .The 24h DCG ,HRT indexes ,including turbulence onset (TO) and turbulence slope (TS) ,were measured and compared among all groups .Results:Compared with normal control group ,there was significant rise in TO [(0.77 ± 0.37)% vs .(1.26 ± 0.92)% ] and significant reduc‐tion in TS [(5.45 ± 4.02) ms/RR interval vs .(1.53 ± 0.70) ms/RR interval] ,P<0.01 both ;significant rise in ab‐normal rates of TO (19.44% vs .42.50% ) ,TS (15.97% vs .31.67% ) and TO + TS (11.11% vs .30.83% ) in SAP group ,P<0.01 all .Compared with single vessel group ,there was significant rise in TO [(0.66 ± 0.22)% vs .(1.28 ± 1.11)% vs .(1.46 ± 1.20)% ] and significant reduction in TS [ (2.04 ± 0.82) ms/RR interval vs .(1.66 ± 0.38) ms/RR interval vs .(1.29 ± 0.58) ms/RR interval] in double‐vessel group and multi‐vessel group ,and TO of multi‐vessel group was significantly higher than that of double‐vessel group ,TS of multi‐vessel group was significantly low‐er than that of double‐vessel group , P<0.01 all .Conclusion:Sinus heart rate turbulence can be used as risk predic‐tor for aged patients with stable angina pectoris ,which can provide basis for clinical effective treatment and progno‐sis assessment .

AIM:To detect the changes of active status of bypass signaling pathways in EML4-ALK positive lung cancer cell line H3122 treated with alectinib, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), and to explore the potential mechanisms.METHODS:EML4-ALK positive cell line H3122 was treated with increasing concentrations of alectinib or/and induced by HGF, EGF and TGF-α.The cell viability was measured by CCK-8 assay.The cell apoptosis was analyzed by flow cytometry.The protein levels and phosphorylation status of ALK, c-Met and EGFR, and the downstream molecules AKT, ERK, p-AKT and p-ERK were examined by Western blot.RESULTS:The viability of the H3122 cells was inhibited by alectinib in a dose-dependent manner after administrated for 72 h, and the IC50 value was 0.042 μmol/L.The concentration-growth curves of the H3122 cells shifted to the right after induced by HGF, EGF and TGF-α.After treatment with alectinib at 0.05 μmol/L for 48 h, the apoptotic rate of H3122 cells was (20.12±1.36)%, while the apoptotic rates of the cells in the groups of alectinib combined with HGF, EGF or TGF-α were (7.85±1.03)%, (5.60±0.79)% and (4.58±1.00)%, respectively.Those values were remarkably lower than those in alectinib single treatment group (P<0.05).Alectinib inhibited the protein levels of p-ALK and its downstream signaling pathway molecules, while HGF significantly up-regulated the protein levels of p-Met and its downstream p-AKT and p-ERK.Besides, EGF and TGF-α remarkablely up-regulated the protein levels of p-EGFR and its downstream p-AKT and p-ERK.Combined treatment with crizotinib and 17-DMAG successfully inhibited the viability of the H3122 cells even in the presence of the HGF and EGFR ligands, respectively.CONCLUSION:Bypass signaling pathways are activated by HGF, EGF and TGF-α in EML4-ALK positive lung cancer cell line H3122, which may be linked to alectinib resistance.

Objective To investigate the effect of oxytocin combined with misoprostol in the prevention of postpartum hemorrhage of uterine contraction,and to provide reference for clinical treatment.Methods 150 women who underwent cesarean section were randomly divided into observation group and control group,75 cases in each group.The two groups were all in the expulsion of the fetus after injection of oxytocin in the uterine wall.The control group after delivery of the placenta received oxytocin intravenous infusion in the prevention and treatment of postpar-tum hemorrhage,the observation group used misoprostol under the tongue to prevent postpartum hemorrhage.The inci-dence of bleeding and postpartum hemorrhage was compared between the two groups.The effective rate and incidence rate of adverse reactions of the two groups were compared.Results The bleeding volume of the observation group was (348.06 ±218.36) mL,and the incidence rate of postpartum hemorrhage was 2.67%,which were significantly lower than the control group (t=5.25,χ2 =12.37,all P<0.05).The effective rate of the observation group was 64%,the total effective rate was 93.33%,the total effective rate was significantly higher than that in the control group (χ2 =10.671,9.22,all P<0.05).1 case of nausea and vomiting occurred in the control group,2 cases had fever,the incidence rate of adverse reactions was 4.00%.5 cases in the observation group had nausea and vomiting,3 cases had fever,the incidence rate of adverse reactions was 10.67%.The incidence of adverse reactions had no significant difference between the two groups.Conclusion Oxytocin combined with misoprostol can significantly reduce the amount of postpartum hemorrhage,reduce the incidence of postpartum hemorrhage,and less adverse reactions,it is the effective treatment for prevention and treatment of uterine contraction fatigue postpartum hemorrhage.

AIM: To investigate the role of HGF/c-Met signaling pathway in crizotinib-induced apoptosis of different lung carcinoma cell lines and to analyze its potential regulatory mechanisms .METHODS: EML4-ALK positive cell line H2228, c-Met proliferation cell line H1993 and control cell line A549 were treated with crizotinib at different doses for different time periods .The viability of the cell lines was measured by MTT assay .The apoptosis was analyzed by flow cytometry with PI staining.The protein levels of MET and phosphorylated MET (p-MET) of HGF/c-Met signaling pathway as well as its down-stream key proteins AKT , ERK, p-AKT and p-ERK in the cell lines before and after crizotinib treatment were examined by Western blot .RESULTS:The growth of H1993, H2228 and A549 cell lines was inhibited after crizoti-nib treatment for 72 h in a dose-dependent manner .Apoptotic rates of H1993 cells and H2228 cells were increased with the crizotinib concentration and exposure time .Down-regulation of p-MET, p-AKT and p-ERK at protein levels in H1993 cells and H2228 cells after exposure to crizotinib for 72 h was confirmed by Western blot .No obvious change of the related-pro-teins of HGF/c-Met signaling pathway was found in A 549 cell line.CONCLUSION: HGF/c-Met signaling pathway may contribute to crizotinib-induced apoptosis of H1993 cells and H2228 cells, which provides the experimental basis for MET-targeting treatment of lung cancer .

Objective Using CT three-dimensional image technique to observe the pulmonary vein stenosis of circumferential pulmonary vein ablation (CPVA) for atrial ifbrillation (AF) on the structure of pulmonary vein before and after radiofrequency ablation. Methods 28 patients with AF who underwent CPVA were followed-up for a mean (6.5±3.9) months.The results of Pulmonary vein morphology study was compared with analysis of preablation, after following up radiofrequency catheter alation (6.5±3.9) months. Pulmonary vein diameters, cross-sectional area and left atrial volume were measured before and after CPVA using 64-slice multidector computed tomography (CT). Results Mild stenosis of pulmonary vein maximum diameter and pulmonary minimum diameter were 61.6%and 56.3%after CPVA. Moderate stenosis of pulmonary vein maximum diameter and pulmonary minimum diameter were 3.6%and 5.4%. All patients does not present symptoms of pulmonary vein stenosis at rest on during excercise during follow up. Conclusions Mild and moderate asymptomatic pulmonary vein stenosis may present in some patients after CPVA.

AIM:To investigate the mammalian target of rapamycin ( mTOR) signaling pathway as the center playing a role in the crizotinib-induced apoptosis of non-small cell lung cancer (NSCLC) cell line H2228, which represents positive echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene. METHODS:H2228 cells were processed according to different purposes .Fluorescence quantitative PCR is used to ob-serve the gene states .MTT assay is used to detect the cell inhibition rates .The cell apoptosis and cell cycle were analyzed by flow cytometry .The expression and activation levels of the key proteins in the mTOR signaling pathway were determined by Western blotting .RESULTS:Crizotinib promoted the apoptosis of H 2228 cells in a time-and dose-dependent manner . Crizotinib blocked the H2228 cells staying at the G1 phase.In apoptotic H2228 cells processed with crizotinib, the activa-tion level of mTOR was decreased , and the activation levels of the key proteins in upstream and downstream of mTOR path -way were both declined .The expression level of the fusion protein EML 4-ALK variant 3 was not affected , but its active form of p-ALK was significantly suppressed .CONCLUSION:mTOR signaling pathway has a certain relationship with the crizotinib-induced apoptosis of lung cancer cell H 2228, which represents positive EML4-ALK fusion gene.

Objective To improve the quality standard for Xielixiao Pills. Methods Rhizoma coptidis, Radix paeoniae alba, Fructus evodia, Poria were identified by TLC. The content of Berberine Hydrochloride was determined by HTLC. Results The identification and content determination methods were simple, accurate, exclusive, and with good reproducibility. Conclusion The improving quality standard can control the quality of this product effectively.