Activation of Toll-like receptor 7 provides cardioprotection in septic cardiomyopathy-induced systolic dysfunction.

BACKGROUND: As a pattern recognition receptor, Toll-like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of TLR7 in septic cardiomyopathy remain unknown. This study aims to determine the role of TLR7 in cardiac dysfunction during sepsis and explore the mechanism of TLR7 in septic cardiomyopathy. METHODS: We generated a mouse model of septic cardiomyopathy by challenging with lipopolysaccharide (LPS). TLR7-knockout (TLR7-/- ), wild-type (WT) mice, cardiac-specific TLR7-transgenic (cTG-TLR7) overexpression, and littermates WT (LWT) mice were subjected to septic model. Additionally, to verify the role and mechanism of TLR7 in vitro, we transfected neonatal rat ventricular myocytes (NRVMs) with Ad-TLR7 and TLR7 siRNA before LPS administration. The effects of TLR7 were assessed by Ca2+ imaging, western blotting, immunostaining, and quantitative real-time polymerase chain reaction (qPCR). RESULTS: We found that TLR7 knockout markedly exacerbated sepsis-induced systolic dysfunction. Moreover, cardiomyocytes isolated from TLR7-/- mice displayed weaker Ca2+ handling than that in WT mice in response to LPS. Conversely, TLR7 overexpression alleviated LPS-induced systolic dysfunction, and loxoribine (TLR7-specific agonist) improved LPS-induced cardiac dysfunction. Mechanistically, these optimized effects were associated with enhanced the adenosine (cAMP)-protein kinase A (PKA) pathway, which upregulated phosphorylate-phospholamban (p-PLN) (Ser16) and promoted sarco/endoplasmic reticulum Ca2+ ATPase (Serca) and Ryanodine Receptor 2 (RyR2) expression in the sarcoplasmic reticulum (SR), and ultimately restored Ca2+ handling in response to sepsis. While improved Ca2+ handling was abrogated after H89 (a specific PKA inhibitor) pretreatment in cardiomyocytes isolated from cTG-TLR7 mice. Consistently, TLR7 overexpression improved LPS-induced Ca2+ -handling decrement in NRVMs. Nevertheless, TLR7 knockdown showed a deteriorative phenotype. CONCLUSIONS: Our data demonstrated that activation of TLR7 protected against sepsis-induced cardiac dysfunction through promoting cAMP-PKA-PLN pathway, and we revealed that TLR7 might be a novel therapeutic target to block the septic cardiomyopathy and support systolic function during sepsis.

Sirtuin 6: A potential therapeutic target for cardiovascular diseases.

Cardiovascular diseases (CVDs) are serious diseases endangering human health due to high morbidity and mortality worldwide, and numerous signal molecules are involved in this pathological process. As a member of the Sirtuin family NAD +-dependent deacetylases, indeed, Sirtuin 6 (SIRT6) plays an important role in regulating biological homeostasis, longevity, and various diseases. More importantly, SIRT6 performs as an indispensable role in glucose and lipid metabolism, inflammation and genomic stability for the occurrence and development of various CVDs. Recent advances: among sirtuins, SIRT6 was frequently unveiled thanks for its protective roles against heart failure, cardiovascular remodeling and atherosclerosis, and identified as an essential intervention target of CVDs, bringing SIRT6 into the focus of clinical interest. Herein, we provide an overview of the current molecular mechanism through which SIRT6 regulates CVDs, and we highlight a potential therapeutic target for CVDs.

Analysis of risk factors for death in patients with corona virus disease 2019 / 中华传染病杂志

Objective:To investigate the risk factors for death in patients with corona virus disease 2019 (COVID-19).Methods:The clinical data of 141 cases of patients diagnosed with COVID-19 at Renmin Hospital of Wuhan University from February 1 to February 26, 2020 were included in this retrospective analysis. The gender, age, time of hospitalization after the onset, clinical manifestations, underlying diseases, laboratory examination indicators (inculding white blood cell counts, neutrophil counts, lymphocyte counts, lymphocyte subsets, immunoglobulin, complement 3, complement 4, D-dimer, fibrinogen), and short term prognosis were compared between the death group and the survival group. Logistic regression was used to analyze the factors influencing the death of COVID-19 patients. The t test, Mann Whitney U test or chi-square test were used for comparison between groups. Results:Of the 141 COVID-19 patients, 52 died and 89 survived. The age, hypertension, chronic respiratory diseases, cardiovascular and cerebrovascular diseases, fever and wheeze of patients in the death group were all higher than those in the survival group, which were (70.7±13.3) years old vs (50.4±15.3) years old, 51.9%(27/52) vs 14.6%(13/89), 15.4%(8/52) vs 4.5%(4/89), 30.8%(16/52) vs 7.9%(7/89), 80.8%(42/52) vs 61.8%(55/89) and 50.0%(26/52) vs 25.8%(23/89), respectively. The differences were all statistically significant ( t=7.972, χ2=22.104, 3.615, 12.392, 5.503 and 8.447, respectively, all P<0.05). The white blood cell count, neutrophil count, CD4 + /CD8 + T lymphocyte, immunoglobulin E, D-dimer, fibrinogen, CD19 + T lymphocyte proportion and CD19 + T lymphocyte count of patients in the death group were all higher than those in the survival group, which were 8.20(5.26, 13.01)×10 9/L vs 5.29(3.96, 7.04)×10 9/L, 7.40(4.54, 11.46)×10 9/L vs 3.16(2.20, 5.01)×10 9/L, 2.32(1.77, 3.11) vs 1.63(1.25, 2.08), 125.0(42.6, 275.0) IU/mL vs 66.8(38.3, 143.0) IU/mL, 7.27(2.11, 16.21) mg/L vs 0.95(0.38, 2.54) mg/L, 4.37(2.72, 6.78) g/L vs 4.10(2.78, 4.97) g/L, (23.19±13.43)% vs (15.38±6.38)%, and (181.5±115.4)/μL vs (98.89±77.64)/μL, respectively. The differences were all statistically significant ( Z=3.944, 4.210, 2.834, 1.190, 5.497, 1.180, t=3.987, 3.411, respectively, all P<0.05). The lymphocyte count, CD3 + T lymphocyte proportion, CD3 + T lymphocyte count, CD8 + T lymphocyte proportion, CD8 + T lymphocyte count, CD16 + CD56 + T lymphocyte count and CD4 + T lymphocyte count were all lower than those in survival group, which were 0.47(0.37, 0.96)×10 9/L vs 1.33(0.90, 1.55)×10 9/L, 48.72%(42.31%, 76.92%) vs 69.91%(65.05%, 75.36%), 223.0(100.0, 403.0)/μL vs 761.0(499.0, 1 092.0)/μL, 13.82%(10.32%, 19.82%) vs 24.90%(20.87%, 29.57%), 55.5(30.5, 106.0)/μL vs 318.0(162.5, 443.5)/μL, 63.0(29.0, 99.5)/μL vs 140.0(69.5, 195.5)/μL and (209.74±140.13)/μL vs (487.61±232.02)/μL, respectively. The differences were all statistically significant ( Z=6.937, 3.944, 5.883, 3.924, 5.703, 3.517 and t=7.558, respectively, all P<0.01). Age, history of hypertension, white blood cell count, D-dimer, and fibrinogen were the risk factors for death of COVID-19 (odds ratio ( OR)=1.170, 10.405, 3.055, 1.128 and 1.343, respectively, all P<0.05). Conclusion:Age, underlying hypertension, white blood cell count, D-dimer and fibrinogen are independent prognostic factors for COVID-19.

TBX20 - an important target gene for the prevention and treatment of cardiovascular diseases / 中华医学遗传学杂志

The T-Box transcription factor family plays a crucial role during heart development. A large amount of clinical evidence showed TBX 1, 2, 5, 18, 20 proteins to be strongly associated with human congenital heart diseases including atrial septal defect, mitral valve disease, and tetralogy of Fallot. Among these, TBX20 has attracted much attention. This article gives a brief review for the progress made in the research on TBX20 and cardiovascular disease.

Matrine attenuates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity maintaining AMPK/UCP2 pathway

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.

Analysis and experience of 578 cases of intraoperative telepathology consultation / 中华内分泌外科杂志

Objective To explore the application value of telepathological consultation in helping grassroots hospitals.Methods 578 cases of intraoperative telepathology consultation were reviewed,and the accuracy and the timely rate of diagnosis were calculated.The systematic distribution,benign and malignant distribution,and the distribution difference in different primary hospitals were analyzed,so as to evaluate the popularization value of the intraoperative telepathology consultation.Results The accuracy rate of 578 cases of intraoperative telepathology consultation was 99.83％.The timely rate of consultation in 30min was 96.02％,and most reports could be diagnosed in 2 to 5 mins.The source of tissues involved in consultation were thyroid,breast,ovary/fallopian tube and lung.In all cases,24.39％ of the malignant tumors were found.Among the diseases of different systems,the proportion of malignant tumors is the highest in breast diseases,followed by lung,thyroid and ovary.Among the four hospitals with most of the consultations,the rate of malignant tumor in Renmin Hospital of Jianli County was the highest,followed by Renmin Hospital of Yingshan County,Renmin Hospital of Xiaochang County,and Fifth Division Hospital of Xinjiang.Conclusion Intraoperative telepathology consultation can provide accurate and timely expert consultation for grassmots hospitals,avoid the "second operations" of the patients,improve the access of medical treatment for people living in relatively remote areas,solve the shortage of pathologists at the grassroots hospitals,and improve the level of doctors' diagnosis and treatment at the grassroots hospitals,which is worth popularizing and applying in Pathology Department of the grassroots hospitals.

Effect of Evodiamine on Hypoxia Induced Cardiomyocytes Injury / 中国药师

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.

Expression Alteration of PLP2 in the Process of Cardiac Remodeling / 医学研究杂志

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.

Research advances in the role of polyamine metabolism in aging and heart failure / 中华老年医学杂志

The incidence of aging-induced heart failure has increased.Spermidine,spermine,and putrescine,the intermediate metabolites of polyamine metabolism,not only participate in an array of crucial molecular interactions with DNA,RNA,and proteins involved in gene transcription and cell division,but also change with aging and age-associated cardiac dysfunction.Detection of serum polyamine metabolites and B type natriuretic peptide(BNP)may open up new ways for the assessment of aging and aging-induced cardiac dysfunction.

Mechanism of cucurbitacin B underlying pressure overload-induced myocardial fibrosis / 中华老年心脑血管病杂志

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.

Value of QT Dispersion in Myocardial Remodeling and Prognosis in Heart Failure Patient with Preserved Ejection Fraction / 医学研究杂志

Objective To evaluate the value of QT dispersion in myocardial remodeling and prognosis in patients with chronic heart failure with preserved ejection fraction (HFpEF).Methods Totally 76 patients admitted to hospital due to HFpEF in the period between years 2013-2015 were recruited.A 12-lead ECG,chest radiograph,echocardiogram,and serum for biochemical analysis were obtained at baseline.Patients were followed for 10.3 ± 2.6 months,the basic information of patients,medication details,laboratory examination,echocardiography and other clinical data,and the mortality rate and the incidence of the disease were collected and analyzed.Results During the follow-up,11 patients died (14.5％) with QT dispersion for 81.6 ± 25.7ms.65 patients survived,including 27 cases of readmission for cardiovascular events (35.5％) with QT dispersion for 73.8 ± 24.7ms.The remaining 38 patients without cardiovascular events (50％) with QT dispersion 64.8 ± 28.7ms.Univariate analysis showed that QTcmax and QTcd were the risk factors for death and cardiovascular events in HFpEF patients (P ＜ 0.05).Cox's proportional hazards regression model analysis found that QTcd was the independent risk factors for death and cardiovascular events in HFpEF patients (P ＜ 0.05).Pearson's correlation analysis showed that QTcd was significantly related with left ventricular end systolic diameter (P ＜ 0.05),left ventricular end diastolic diameter (P ＜ 0.05).Conclusion QT dispersion has clinical value in the diagnosis of myocardial remodeling and prognosis in patients with HFpEF.

Expression Alteration of SSR in the Process of Cardiac Remodeling / 医学研究杂志

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.

Effect of lycopene on H9c2 cell apoptosis induced by angiotensin Ⅱ / 中华老年医学杂志

Objective To investigate the effect of lycopene (Lyc) on H9c2 cell apoptosis induced by angiotensin Ⅱ (Ang Ⅱ).Methods Using Ang Ⅱ (10 μmol/L) to stimulate H9c2 cells,we observed the protective effect of Lyc on H9c2 cells apoptosis.The H9c2 cells viability induced by different consideration of Lyc or Ang Ⅱ or both was detected by CCK8 assay.The expression levels of Bax and Bcl-2 in H9c2 cells were determined by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR).Western blot was conducted to detect the protein expressions of Bax,Caspase 3,Caspase 9 and Bcl-2 in H9c2 cells.The apoptotic ratio of H9c2 cells was observed by TUNEL assay.Results Compared with control group,Ang Ⅱ could decrease the viability of H9c2 cells to (92.87±4.37)％.The result of RT-PCR showed that Ang Ⅱ decreased the expression level of Bcl-2,and Bax level was increased under the stimulation of Ang Ⅱ (P＜0.05),while the expression level of Bcl-2 was increased and Bax level was decreased under the co-stimulation of Ang Ⅱ and Lyc in a concentration dependent manner,which indicated that Lyc ameliorated the apoptosis of H9c2 cells.The result of western blot showed that the protein expressions of Bax,Caspase 3 and Caspase 9 were increased,but Bcl-2 was decreased after the stimulation of Ang Ⅱ (P＜0.05).While these phenomenon reversed apparently under the co stimulation of Ang Ⅱ and Lyc.A large number of apoptotic cells were observed under the stimulation of Ang Ⅱ through TUNEL assay.But the number of apoptotic cells reduced significantly under the co-stimulation of Lyc and Ang Ⅱ (P ＜0.05).Conclusions Lyc ameliorates the H9c2 cell apoptosis induced by Ang Ⅱ,which indicates that Lyc may have an important role in the treatment of various cardiovascular diseases.

Lycopene attenuates angiotensin II induced oxidative stress in H9c2 cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of Lycopene (Lyc) on Ang II induced oxidative stress in H9c2 cell line derived from rat cardiac tissue,and to explore related mechanisms.</p><p><b>METHODS</b>H9c2 cells were divided into 6 groups: control group, Ang II group (1 µmol/L), Ang II (1 µmol/L) + low dose Lyc (3.125 nmol/L) group, Ang II (1 µmol/L) + moderate dose Lyc (6.25 nmol/L) group and Ang II (1 µmol/L) + high dose Lyc (12.5 nmol/L) group and Lyc group (12.5 nnmol/L). Cell growth was determined by CCK8 assay, ROS generation was detected using a Microplate reader and Fluorescence microscopy, the expression of NOX2 was determined by Western blot, mRNA expression of p47(phox), SOD1 and SOD2 were determined by Real Time-PCR, MDA was detected by ELISA kit.</p><p><b>RESULTS</b>Compared to control group,cell survival was significantly reduced and ROS generation was significantly increased post Ang II stimulation,cotreatment with Lyc significantly improved cell survival and reduced ROS generation in a dose-dependent manner (all P < 0.01). mRNA expression of SOD1 and SOD2 was significantly downregulated while MDA concentration was significantly increased in Ang II treated cells, which could be significantly reversed by cotreatment with Lyc in a dose dependent manner (all P < 0.01). Protein expression of NOX2 and mRNA expression of p47(phox) were significantly upregulated post Ang II and which could be significantly downregulated by cotreatment with Lyc in a dose-dependent manner (all P < 0.01).</p><p><b>CONCLUSION</b>Lyc could attenuate Ang II induced oxidative stress and this effect is linked with its capacity of reducing ROS generation and enhancing cellular ROS scavenging ability in H9c2 cells.</p>

Practice and experience of the hospital in clinical department management / 中华医院管理杂志

An introduction to the management of clinical departments of the hospital since 2009, featuringthree independence and four unification.The pattern is designed to mobilize department staff′s work enthusiasm,and improve their management efficiency,thus upgrading management of the hospital as a whole.Thanks to such reform,the hospital has scored great outcomes in terms of comprehensive strength,medical quality,disciplinary development and talent cultivation.

Clinical observation of ultrasound guided injection different dosage of thrombin for treatment of ;iatrogenic femoral artery pseudoaneurysm / 中国介入心脏病学杂志

Objective To investigate the efifcacy and adverse effect of ultrasound-guided injection of different dosage of thrombin in the treatment of femoral artery pseudoaneurysm formed after vascular intervention. Methods 48 cases of femoral artery pseudoaneurysm after vascular interventional operation in our hospital were randomly divided into two groups according to the dosage thrombin given.Under ultrasound guidance, patients in the observation group (n=24) received injection thrombin 100U/ml while patients in the control group received injection of thrombin 500U/ml.All the operational procedures were identical between the 2 groups. Results No statistical differences were found in clinical characteristics, total number injection needed and operation time between two groups.Recurrence pseudoaneurysm was noted in 1 cases in the observation group. 2 cases of superifcial femoral arteries thrombin and 1 case of fever were recorded in control group. There was no difference in adverse event rates between the 2 group. Conclusions Ultrasound-guided injection with low dose thrombin in the treatment of post interventional femoral artery pseudoaneurysm is equally effective as higher dose.

Effects of lentiviral-mediated p38 mitogen-activated protein kinase short hair-pin RNA on cardiac function after myocardial infarction in aldosterone overload rats / 中华老年医学杂志

Objective To investigate the effects of p38 mitogen-activated protein kinase (MAPK) short hair RNA (shRNA) delivered by lentiviral vectors (pGLV) on cardiac function after myocardial infarction (MI) in aldosterone overload rats and to explore the mechanism.Methods Aldosterone overload rat myocardial infarction model was obtained by ligating the left anterior descending coronary artery.The pGLV-shRNA was constructed,sequenced and injected into rats via tail vein.Rats were divided into 3 groups:pGLV-shRNA group (n=6),pGLV-shRNA-NC group (n=6,contained a nonsense shRNA) and the sham-operation group (n=6).Cardiac function was measured by cardiac ultrasound.Apoptosis was assessed by transferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL).The p38 MAPK mRNA expression was analyzed by RT-PCR.The protein expressions of p38 MAPK and caspase-3 were detected by Western blot.Results Compared with the sham-operation group,cardiac systolic function was reduced and myocardial apoptosis index was significantly increased [(31.26 ± 4.45) ％ vs.(15.20 ± 2.18) ％,P ＜ 0.01] in pGLV-shRNA-NC group.The mRNA and protien expressions of p38MAPK and caspase 3 protein expression were significantly increased in pGLV-shRNA-NC group (all P＜0.01).Compared with pGLV-shRNA-NC group,cardiac function was improved,myocardial cell apoptosis index was reduced [(22.35±3.59)％ vs.(31.26±4.45)％,P＜0.05],and the mRNA and protien expressions of p38MAPK and caspase 3 protein expression were decreased in pGLV-shRNA group (all P＜0.05).Conclusions Cardiac dysfunction is associated with p38MAPK-mediated myocardial apoptosis in aldosterone overload MI rats.pGLV-shRNA may inhibit cardiomyocyte apoptosis and improve postMI cardiac function.

Time and risk factors for spontaneous closure of patent ductus arteriosus in preterm infants / 中华围产医学杂志

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.

Early administration of trimetazidine may prevent or ameliorate diabetic cardiomyopathy.

Diabetic cardiomyopathy is a type of cardiac dysfunction resulting from diabetes, independent of vascular or valvular pathology. It clinically manifests initially as asymptomatic diastolic dysfunction and then progresses to symptomatic heart failure. Two major contributors to the development of diabetic cardiomyopathy, which are unique to diabetes, are hyperglycemia and diabetes-related alterations in myocardial metabolism. Diabetes mellitus is characterized by reduced glucose and lactate metabolism and enhanced fatty acid metabolism, which are the early consequences of the disease. Studies on the effect of intensive glucose control on heart failure events in patients with diabetes have been conducted with neutral results. However, no study on the effect of metabolic modulators on the prevention of heart failure has been reported. Trimetazidine, a 3-ketoacyl coenzyme A thiolase (3-KAT) inhibitor, shifts cardiac energy metabolism from free fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-KAT, and is used clinically as an effective antianginal agent. Studies have shown that trimetazidine improves heart function in patients with idiopathic cardiomyopathy and in diabetic patients with cardiac ischemia or heart failure. In addition to being effective, trimetazidine has only mild side effects. Therefore, instead of routine administration of trimetazidine for the treatment of diabetic cardiomyopathy, we hypothesize that the early application of trimetazidine may prevent or ameliorate diabetic cardiomyopathy. In addition to life style modifications, ACEI, ARB, and beta-blockers, which have been recommended in the past, trimetazidine should be administered to those patients with impaired glucose tolerance or patients in the early course of diabetes. In this way, we may reduce the prevalence of heart failure and improve the long-term survival of patients with diabetes through early normalization of the myocardial substrate metabolism.

Dynamic change and correlation of ventilative function pulmonary mechanics with cardiac function in the term infants / 中国小儿急救医学

Objective To investigate the dynamic change and correlation of the pulmonary ventilative function, mechanic and cardiac function in the term infants. Methods Twenty hundred term infants were divided into A 、B 、C and D groups by age which was 0 ～ 24 h, ～ 72 h, ～ 1 w and 28 d respectively. The lung ventilative and mechanical function were measured respectively by using techniques of tidal breathing flow-volume loop(TBFVL)and the single occlusion. The Master screen Paed-lung function devices of Germanic JAEGER Co. was be used in this study. The parameter of pulmonary function including minute volume(MV) ,tidal volume (TV), respiratory system compliance(Crs) and respiratory system resistance (Rrs). The cardiac function were measured by using SonoSite 180 PLUS color Doppler ultrasonic diagnostic apparatus. The main parameter of cardiac function including cardiac output(CO) and stroke volume(SV). Results The TV of A, B ,C and D group were 20. 2 ± 3.78,21. 1 ± 3.71,22. 3 ± 4. 48 and 23. 9 ±4.90 (ml)respectively, the TV of C and D group were higher than that of A group, and the TV of D group was higher than that of B group (P ＜ 0. 05).There were no significantly difference of Crs, Rrs among A, B, C and D group(P ＞ 0. 05). The CO of A,B,C and D group were 0.93 ±0. 23,0.93 ±0.23,1.02 ±0.21 and 1.08 ±0.27 (L/min) ,the CO of D group was higher than that of A and B groups (P ＜ 0. 05). The CO was negative correlation with Rrs (r = - 0. 16,P ＜ 0. 05) and positive correlation with MV、 TV、 Crs (r was 0. 50、 0. 54、0. 13 respectively, P ＜ 0. 05).Conclusion The lung ventilative function is mature gradually with increasing age. The cardiac output has been obviously improved for postnatal 1 week in the term infants. The pulmonary ventilative function and mechanic parameter are important effective factors of cardiac function.