Objective To investigate the role and underlying mechanism of cathepsin B in myocar-dial injury in mice with diabetic cardiomyopathy(DCM).Methods Twenty 8-week-old male SPF C57BL/6 mice were randomly divided into wild-type(WT)group and WT DCM group,with 10 mice in each group.Another 20 8-week-old male SPF-grade mice with cathepsin B knockout(KO)were randomly and equally assigned to KO group and KO DCM group.HE staining was used to observe morphological changes,Prussian blue staining was employed to detect iron deposition,while immunohistochemical staining with 4-hydroxynonenal(4-HNE)was used to assess lipid peroxidation level in the myocardial tissues.Western blotting was performed to detect the expression of heme oxygenase-1(HO-1),superoxide dismutase 2(SOD2),and nuclear factor E2-related factor 2(Nrf2),while RT-PCR was applied to evaluate the expressions of Nrf-2,HO-1,and phospholipid hydroperoxide glutathione peroxidase 4(GPX4).Results Compared to the WT DCM group,the KO DCM group presented improved cell arrangement in cardiac tissues and sig-nificant reduction in inflammatory cell infiltration.Furthermore,the KO DCM group displayed a significant decrease in iron deposition compared to the WT DCM group.Additionally,the KO DCM group exhibited a significant reduction in 4-HNE expression compared to the WT DCM group.The protein levels of Nrf2,SOD2,and HO-1 were significant increased in the KO DCM group than the WT DCM group(0.68±0.21 vs 0.39±0.13,0.59±0.10 vs 0.28±0.09,1.03±0.10 vs 0.48±0.04,P＜0.05).Moreover,elevated mRNA levels of GPX4,Nrf2 and HO-1 were also observed in the KO DCM group than the WT DCM group(0.65±0.09 vs 0.40±0.10,0.61±0.11 vs 0.34±0.11,0.62±0.12 vs 0.39±0.09,P＜0.05).Conclusion Cathepsin B exacerbates myocardial injury in DCM mice through ferroptosis.

Oxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as control. H9C2 cells were used to verify the effect of matrine . DOX injection triggered increased generation of reactive oxygen species (ROS) and excessive cardiomyocyte apoptosis, which were significantly mitigated by matrine. Mechanistically, we found that matrine ameliorated DOX-induced uncoupling protein 2 (UCP2) downregulation, and UCP2 inhibition by genipin could blunt the protective effect of matrine on DOX-induced oxidative stress and cardiomyocyte apoptosis. Besides, 5'-AMP-activated protein kinase 2 () deficiency inhibited matrine-mediated UCP2 preservation and abolished the beneficial effect of matrine in mice. Besides, we observed that matrine incubation alleviated DOX-induced H9C2 cells apoptosis and oxidative stress level activating AMPK/UCP2, which were blunted by either AMPK or UCP2 inhibition with genetic or pharmacological methods. Matrine attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity maintaining AMPK/UCP2 pathway, and it might be a promising therapeutic agent for the treatment of DOX-induced cardiotoxicity.

Objective To study the mechanism of cucurbitacin B (CuB) underlying pressure over load-induced myocardial fibrosis.Methods Sixty C57 mice were divided into sham operation group,CuB treatment group,aorta ligation group,CuB+aorta ligation group (15 in each group).The animals received intragastric gavage (0.2 mg/kg · 2 d) one week after operation and a myocardial fibrosis model of mice was induced by aorta ligation 4 weeks after operation.Microvascular density (MVD) was detected with immunohistochemical staining.Expressions of α-SMA,CD31,CD34,vimentin and endothelial-mesenchymal transition (EndMT) were detected by Western blot with immunofluorescence staining.Results No significant difference was found in cardiac MVD,and expression level of α-SMA,vimentin,CD31 and CD34 between sham operation group and CuB group 4 weeks after operation (P＞0.05).The cardiac MVD and expression level of CD31 and CD34 were significantly lower while the expression level of α-SMA and vimentin was significantly higher in aorta ligation group than in sham operation group 4 weeks after operation (P＜0.05).The cardiac MVD and expression level of CD31 and CD34 were significantly higher while the expression level of α-SMA and vimentin was significantly lower in CuB+aorta ligation group than in aorta ligation group 4 weeks after operation (P＜0.05).Conclusion CuB can attenuate cardiac fibrosis by regulating EndMT.

Objective:To investigate the protective effect of evodiamine on cardiomyocytes hypoxia injury. Methods:H9c2 myo-cardial cells were exposed to hypoxia for 24 h to induce myocardial cell injury model. The cells were pretreated with different concentra-tions of evodiamine for 12 h. The cardiomyoctes viability was detected by CCK-8 assay. The transcription of inflammatory cytokines was detected by RT-PCR. The cardiomyocyte apoptosis was detected with Tunel staining. The alteration of signal pathway was detected by immunoblotting. Results:Four concentrations of evodiamine did not affect the activity of cardiomyocytes in the basal condition (P>0.05). After 24-hour hypoxia,the viability of cardiomyocytes decreased significantly when compared with that in the control group with significant difference (P<0.05) among 1,5 and 10 μmol·L-1evodia in a dose-dependent manner. The transcription of pro-inflam-matory cytokines(TNF-α,IL-1 and IL-6) significantly increased and the cells apoptosis increased. Evodiamine pretreatment increased the cell viability after hypoxia injury, reduced the transcription of inflammatory cytokines and reduced the number of apoptotic cells when compared with that in the control group with significant differences(P<0.05) between 1 μmol·L-1and 10 μmol·L-1evodia. The results of western blot showed that evodiamine activated AMPKα and AKT, inhibited the activity of NF- kappa B, and compared with the control group,there were significant differences(P<0.05) between 1 μmol·L-1and 10 μmol·L-1of evodia. Conclusion:Evodiamine can protect cardiomyocytes from hypoxia injury and may become a new anti-myocardial ischemia drug.

Objective To investigate the expression of PLP2 protein in the process of cardiac remodeling.Methods Mice were subjected to left anterior descending coronary artery ligation to induce cardiac remodeling model.Mice were subjected to isoproterenol (ISO) subcutaneous injection for 2 weeks to establish acute cardiac injury model.Mice were subjected to aortic banding (AB) surgery to establish a myocardial hypertrophy model.Cardiac myocytes hypertrophy model was induced by phenylephrine (PE) stimulation.Transforming growth factor (TGF) beta was used to stimulate cardiac fibroblasts.The PLP2 transcription level was detected by RT-PCR.Results PLP2 expression was significantly increased in 2 weeks after myocardial infarction (P ＜ 0.05),as well as in acute cardiac injury induced by ISO injection (P ＜ 0.05).After 1 week of AB surgery,the PLP2 expression began to increase (P ＜ 0.05),peaked at 2 weeks post AB (P ＜ 0.05),preserved to 8 weeks after AB (P ＜ 0.05).The expression of PLP2 in PE stimulated cardiomyocytes was increased as well as TGFβ stimulated fibroblast.Conclusion The expression of PLP2 were dynamically changed significantly in different cardiac remodeling model,suggesting that it may be involved in the occurrence and development of cardiac remodeling.

Objective To investigate the expression changes of SSR in the process of cardiac remodeling.Methods Myocardial infarction (MI) was induced by left anterior descending coronary artery ligation in mice to establish cardiac remodeling model.Mice subjected to isoproterenol (ISO) subcutaneous injection for 2 weeks to establish acute cardiac injury model.Mice subjected to aortic banding (AB) to establish a mouse model of cardiac hypertrophy.RT-PCR was used to detect the expression change of SSR in various cardiac remodeling models.Results The expression levels of SSR subunit 1 (SSR1) and 3 (SSR3) were significantly decreased in mice after 2 weeks of MI (P ＜ 0.05),and were also decreased in acute cardiac injury induced by 2 weeks of ISO injection (P ＜ 0.05),and reduced afterl week of AB operation (P ＜ 0.05).However,the expression of SSR1 and SSR3 increased at 2 weeks after AB (P ＜ 0.05),and sustained to 8 wccks after AB (P ＜ 0.05).Conclusion The expression of SSR3 and SSR1 in different models of cardiac remodeling were significantly changed,and showed dynamic changes,suggesting that it may participate in the occurrence and development of cardiac remodeling.

Objective To explore the impact of preoperative neoadjuvant chemotherapy on the expressions of multi-drug resistance genes in patients with cervical cancer and its relationship with the effect of chemotherapy. Methods Ninety-eight cervical cancer patients with TP regimen selected to perform preoperative chemotherapy were enrolled in the Affiliated Hospital of Guiyang Medical College between January 2010 and June 2014. Immunohistochemisty (En vision method) was used to determine the expressions of P-gP, GST-π and TopoII of the same patients before and after neoadjuvant chemotherapy and explore the relationship with the effect of chemotherapy. Results The positive expression rates of P-gp and GST-π were 71.43% and 64.29% before chemotherapy and 80.61%and 74.49%after chemotherapy, respectively. The former two had significant differences (P<0.01). The positive expression rates of TopoII was 48.98%before chemotherapy and 28.57%after chemotherapy , respectively, showing significant differences (P < 0.01). The expressions of P-gp, GST-π and TopoⅡ gene were not affected by the clinical and pathological features of cervical cancer (P > 0.05). Before neoadjuvant chemotherapy, the positive expression of GST-π in the ineffective group was statistically higher than that in the effective group (P<0.05). The positive expressions of P-gp and Topo II showed no statistical significance between the effective group and the ineffective group (P > 0.05). There was significant correlation in the expressions of P-gp, GST-π and TopoⅡ(P < 0.05) before and after neoadjuvant chemotherapy. Conclusions The expression of P-gp, GST-πand TopoⅡgene may not be affected by the clinical and pathological features of cervical cancer, but may change expressions of multi-drug resistance genes in cervical cancer by neoadjuvant chemotherapy. Monitoring their expression has a guiding significance for drug selection, prognostic judgment, and the following treatment regimen decision. The GST-π, expression level can be used as a biological parameter to predict the effect of TP regimen neoadjuvant chemotherapy.

Gamma amino butyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. Alterations in GABAergic function are associated with a variety of neurological and psychiatric disorders. However, noninvasive in vivo measurement of GABA is difficult because of its low concentration and the presence of overlapping resonances. To study GABA concentration in the occipital cortex in major depressive disorder (MDD), a group of medication-naive, first episode depressed patients (n = 18, HAMD > 17), and a group of healthy controls (n = 23) were investigated using a Point Resolved Spectroscopy (MEGA-PRESS) on a 3.0 T MR scanner. The results showed that occipital GABA levels were significantly lower (P < 0.001) in the patient group than those in the healthy controls, yet the correlations between the severity of MDD (HAMD, BDI) and the GABA concentration is insignificant. Therefore, our data suggest that patients with first episode, unmedicated MDD have changes in cortical concentrations of GABA. This biochemical abnormality may be a marker of a trait vulnerability to mood disorder, and may explain the visual problem of severe MDD patients.
Adolescent ; Adult ; Depressive Disorder, Major ; metabolism ; Female ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Occipital Lobe ; metabolism ; Young Adult ; gamma-Aminobutyric Acid ; analysis ; metabolism

Objective To investigate the time and risk factors for spontaneous closure of patent ductus arteriosus (PDA) in preterm infants. Methods One hundred and seventy-seven preterm infants with arterial ductus unclosed were divided into three groups according to their gestational age as 28-31+6 weeks group (n=44),32-34+6 weeks group (n=59) and 35-36+6 weeks group (n=74).PDA was diagnosed by echocardiography in time of ≤12 h,-24 h,-48 h,-72 h,-96 h,-120 h,-144 h and ＞144 but ≤168 h after birth.The parameters of cardiac function included peak flow rate of aorta valve orifice,peak flow rate of pulmonary artery valve orifice,cardiac output,stroke volume,ejection fraction,the ratio of early (E) and late (A) diastolic velocities of mitral and tricuspid valves.The risk factors of arterial ductus spontaneous closure were determined by Logistic regression analysis.Results The cumulative spontaneous closure rates of preterm infants in three groups were 95.5％,100.0％ and 100.0％ within 168 h after birth respectively. There were significant differences of cumulative spontaneous closure rate in different time among three groups (x2 =4.23,7.45,12.46,7.14,4.75,6.47,3.89 and 3.89 respectively,P＜0.05).After spontaneous closure of PDA during 12-24 h, peak flow rate of pulmonary artery valve orifice increased [(0.69±0.12) cm/s vs (0.65±0.12) cm/s,t=2.37,P=0.02],peak flow rate of aorta valve orifice [(0.65±0.11) cm/s vs (0.69±0.12) cm/s,t=2.51,P=0.02] and ejection fraction [(63.00±8.50) ％ vs (66.00±8.50) ％,t=2.34,P=0.02] decreased.Logistic regression analysis showed that,the risk factors of preterm infants with arterial ductus unclosed within 24 hours after birth were gestation age (OR =1,825,95％CI:1.239-2.689),1 min Apgar score 0-3 (OR=1.946,95％CI:1.572-3.527) and early onset sepsis (OR=3.215,95％CI:1.245-5.463) ; gestation age (OR=3.270,95％CI:1.852-5.774),twins (OR=3.634,95％CI:1.489-8.871),1 min Apgar score 0-3 (OR=3.752,95％CI:2.156-5.436),Ⅲ-Ⅳ stage of respiratory distress syndrome (OR=2.897,95％CI:1.764-5.348) and early onset sepsis (OR=3.172,95％CI:2.134-6.437) were the risk factors of preterm infants with arterial ductus unclosed during 24-48 hours after birth; and gestational age (OR=2.471,95％CI:1.087-5.613),1 min Apgar score 0-3 (OR=2.985,95％CI: 1.469-5.736), Ⅲ-Ⅳ stage of respiratory distress syndrome (OR =3.645,95％ CI:1.879-6.282),fluid volume excess (OR =4.135,95％CI:2.146-7.428) and early onset sepsis (OR=3.246,95％CI:2.146-4.526) for those with arterial ductus unclosed during 48-72 hours after birth. Conclusions The spontaneous closure rate of arterial ductus in the newborn infants whose gestational age over 28 weeks was above 90％ in the first week after birth.There was no difference of left ventricular pump function between before and after the spontaneous closure.Reducing the incidence of premature birth,twins,severe asphyxia,severe respiratory distress syndrome, fluid excess and early onset sepsis might improve the spontaneous closure of arterial ductus.