Alcohol promotes renal fibrosis by activating Nox-mediated DNA methylation of Smad7 / 中国药理学与毒理学杂志

OBJECTIVE Alcohol is mainly metabolized through liver and excreted by kidney in the body. Kidney damage has been considered as the secondary to liver injury and kidney dysfunction is common in hospitalized patients with severe alcoholic hepatitis. Both acute and chronic alcoholism accumulation can compromise kidney function, although alcoholic kidney disease has drawn much more attention recently,the methodology for establishing the in vivo and in vitro alcoholic renal fibrosis models are still lacking,and the underlying mechanisms are to be determined. METHODS and RESULTS Mice were feed with a liquid diet containing alcohol for 4 weeks, 8 weeks and 12 weeks respectively, results of Masson′s Trichrome staining showed that kidney fibrosis peaked in 8-week model group, which consistent with the results of albumin assay,Western blot,immunostaining and real-time PCR of collagen I and α-SMA.In vitro study also confirmed that ethanol upregulated the level of fibrotic index-es,including collagen I and α-SMA,in tubular epithelial cells(HK2 cells).Additionally,both in vivo and in vitro studies showed that Smad7 was decreased and Smad3 was highly activated. Then we further detected the underlying mechanisms by which alcohol induced the imbalance of Smad7 and Smad3. Results of Genome-wide methylation sequencing found DNA methylation of Smad7 in the alcoholic fibrosis kidney,which may be mainly mediated by DNA methyltransferase 1(DNMT1),because knock-down of DNMT1,but not DNMT2 and 3,largely restored Smad7 level in ethanol-treated HK2 cells.Con-sequently, we found that NADPH Oxidases (nox)-mediated oxidative stress is the major force upregu-lating DNMT1,since knockdown of Nox2 and 4 could both decrease DNMT1 while rebalancing Smad7/Smad3 axis, and thereby relieved ethanol-induced fibrotic response in HK2 cells. More importantly, intraperitoneal injection of apocynin,an inhibitor of NADPH oxidoreductase,attenuated renal fibrosis in alcoholic kidney fibrosis mouse model. CONCLUSION By establishing the novel in vivo and in vitro models,we found that through activating oxidative stress-induced DNA methylation of Smad7,alcohol induces renal fibrosis by breaking the balance between Smad7 and Smad3.Elimination of Nox-mediated oxidative stress may be a potential therapy for treatment of long-term alcohol abuse-induced kidney fibrosis.

Supervision effect analysis on clinical use of antibacterials in medical institutions of Jinshan District of Shanghai / 上海预防医学

Objective ] To investigate the application and management of antibacterials in hospitals under our administration. [ Methods] All medical institutions under our administration were investigated and supervised for their organizational system in clinical use of antibacterials and for their use of antibacterials in outpatients and inpatients. [ Results ] All hospitals under our administration had improved their medical management organization and related systems, and the proportion of antibacterial usage in outpatients and inpatients had been reduced. [ Conclusion] The clinical usage of antibacterials has been gradually standardized, but there is much to be desired.And supervision and training need to be enhanced in this regard.

A systematic review and meta-analysis on efficacy and safety of cardiac resynchronization therapy alone or in combination with implantable cardioversion defibrillation in patients with mild to severe heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of cardiac resynchronization therapy (CRT) alone or in combination with implantable cardioversion defibrillation (ICD) in patients with mild to severe heart failure.</p><p><b>METHOD</b>Electronic searches of MEDLINE, EMBASE, CENTREN and affiliated clinical trial registration data center, US Food and Drug Administration reports, CBMdisc, VIP, and CNKI databases from establishment to Dec 2010, using the search terms "CRT, heart failure", "biventricular pacer, heart failure", "biventricular pacing, heart failure", and "biventricular pacemaker, heart failure", were performed to identify randomized controlled trials (RCTs). Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included RCTs.</p><p><b>RESULTS</b>A total of 23 trials including 8521 patients were included. In patients with New York Heart Association (NYHA) class I/II, CRT improved left ventricular ejection fraction (LVEF) [weighted mean difference (WMD) = 0.05, 95% CI 0.01 - 0.08], reduced heart failure hospitalizations [risk ratio (RR) = 0.70, 95%CI 0.61 - 0.81] and all-cause mortality (RR = 0.78, 95%CI 0.65 - 0.93) with increasing complications (RR = 1.74, 95%CI 1.42 - 2.13). In patients with NYHA class III/IV, CRT improved LVEF (WMD = 0.03, 95%CI 0.01 - 0.05), reduced both heart failure hospitalizations (RR = 0.64, 95%CI 0.55 - 0.73) and all-cause mortality (RR = 0.80, 95%CI 0.70 - 0.91) without increasing complications (RR = 1.01, 95%CI 0.91 - 1.12). Compared with ICD alone, CRT in combination with ICD significantly improved LVEF (WMD = 0.03, 95%CI 0.00 - 0.06), reduced heart failure hospitalizations (RR = 0.73, 95%CI 0.64 - 0.82) and all-cause mortality (RR = 0.82, 95%CI 0.72 - 0.95) without increasing complications (RR = 1.36, 95%CI 0.91 - 2.03) in patients with NYHA class I-IV symptoms.</p><p><b>CONCLUSIONS</b>CRT offered additional benefits on top of standard medication for heart failure patients with ventricular dyssynchrony in terms of improving LV function, and reducing heart failure hospitalization and all-cause mortality, regardless of NYHA class. CRT offers also additional benefit in heart failure patients implanted with ICD. However, CRT is associated with more adverse events in patients with NYHA class I/II.</p>

Alteration of interleukin-17/interferon-γ double positive cells in mice with Coxsackie virus induced myocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the alteration of interleukin-17 and interferon-γ double positive cells (IL-17(+)/IFN-γ(+) cells) in mice with coxsackie virus B3 (CVB3) induced acute viral myocarditis (VMC).</p><p><b>METHODS</b>VMC was induced in male Balb/c mice by peritoneal injection of CVB3. Control mice received PBS injection. At 0, 1, 2, 3, 4 and 6 weeks after injection, pathological scores were determined on hematoxylin-eosin stained heart sections and flow cytometric analysis was performed to evaluate the percent of IL-17(+)/IFN-γ(+) cells among CD4(+) T cells.</p><p><b>RESULTS</b>Compared to control mice, the pathological scores of VMC mice were higher on CVB3 infection week 1 (1.8 ± 0.5), peaked on week 2 (2.8 ± 0.5) and declined thereafter. However, the proportion of IL-17(+)/IFN-γ(+) cells remained steadily at a low level throughout the observation period and was similar between VMC and control mice.</p><p><b>CONCLUSIONS</b>Our data shows that IL-17(+)/IFN-γ(+) cells might not be involved in the inflammation process of CVB3 induced VMC mice model.</p>

Diagnostic Value of 64-Slice Dual-Source CT Coronary Angiography in Patients with Atrial Fibrillation: Comparison with Invasive Coronary Angiography

OBJECTIVE: We wanted to evaluate the image quality and diagnostic value of 64-slice dual-source computed tomography (DSCT) coronary angiography in patients with atrial fibrillation (Afib). MATERIALS AND METHODS: The coronary arteries of 22 Afib patients seen on DSCT were classified into 15 segments and the imaging quality (excellent, good, moderate and poor) and significant stenoses (> or = 50%) were evaluated by two radiologists who were blinded to the conventional coronary angiography (CAG) results. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting important coronary artery stenosis were calculated. McNemar test was used to determine any significant difference between DSCT and CAG, and Cohen's Kappa statistics were calculated for the intermodality and interobserver agreement. RESULTS: The mean heart rate was 89 +/- 8.3 bpm (range: 80-118 bpm). A range from 250 msec to 300 msec within the RR interval was the optimal reconstruction interval for the patients with Afib. The respective overall sensitivity, specificity, PPV and NPV values were 74%, 97%, 81% and 96% for reader 1 and 72%, 98%, 85% and 96% for reader 2. No significant difference between DSCT and CAG was found for detecting a significant stenosis (reader 1, p = 1.0; reader 2, p = 0.727). Cohen's Kappa statistics demonstrated good intermodality and interobserver agreement. CONCLUSION: 64-slice DSCT coronary angiography provides good image quality in patients with atrial fibrillation without the need for controlling the heart rate. DSCT can be used for ruling out significant stenosis in patients with atrial fibrillation with its high NPV for detecting in important stenosis.

A meta-analysis on efficacy of anti-platelet agents and anticoagulants for preventing stroke in patients with nonvalvular atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and security of anti-platelet and anticoagulant therapy on prevention of ischemic stroke in patients with nonvalvular atrial fibrillation (NAF).</p><p><b>METHODS</b>We searched PubMed, EMbase, CENTREN and its affiliated clinical trial registration data center, CBMdisc, VIP, and CNKI databases from establishment to Dec 2009 to identify randomized controlled trials (RCTs) covering the use of anti-platelet agents and anticoagulants for patients with NAF. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included RCTs.</p><p><b>RESULTS</b>Fourteen RCTs involving 15 880 patients were include. Compared with placebo or no use of anti-platelet drugs, antiplatelet therapy didn't reduce ischemic stroke (RR = 0.83, 95%CI 0.68 to 1.00, P = 0.05), systemic emboli (RR = 0.71, 95%CI 0.34 to 1.51, P = 0.38) and all-cause mortality (RR = 0.88, 95%CI 0.73 to 1.07, P = 0.21) while significantly increased the major bleeding (RR = 2.88, 95%CI 1.21 to 6.86, P = 0.02) in patients with NAF, intracranial hemorrhage was not affected by antiplatelet therapy in patients with atrial fibrillation (RR = 3.25, 95%CI 0.84 to 12.62, P = 0.09). Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the incidence of ischemic stroke (RR = 1.84, 95%CI 1.48 to 2.28, P < 0.01) and systemic emboli (RR = 1.94, 95%CI 1.24 to 3.03, P = 0.004) but significantly increased the incidence of intracranial hemorrhage (RR = 0.49, 95%CI 0.31 to 0.78, P = 0.003), did not affect all-cause mortality (RR = 1.06, 95%CI 0.90 to 1.23, P = 0.50) and the incidence of major bleeding (RR = 0.95, 95%CI 0.76 to 1.19, P = 0.66) in NAF patients.</p><p><b>CONCLUSIONS</b>Compared with the placebo and no use of anti-platelet drugs, anti-platelet therapy didn't reduce ischemic stroke and systemic emboli but increased the risk of major bleeding in NAF patients. Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the ischemic stroke and systemic emboli without increasing the risk of major bleeding, but significantly increased the incidence of intracranial hemorrhage in NAF patients. Since the study included RCTs with limited and less uniform outcome endpoints, the conclusions should be verified with RCTs with more uniform endpoints and longer follow-up time.</p>

Association between myocardial calpain activation and apoptosis in lipopolysaccharide-induced septic mouse model / 中华心血管病杂志

<p><b>OBJECTIVE</b>in septic mice, myocardial calpain was activated and induced caspase-3 activation, the association between calpain activation and apoptosis was explored in this experiment.</p><p><b>METHODS</b>in in vivo model, adult C57 mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Myocardial calpain and caspase-3 activities, protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were detected by Western blot analysis and myocardial apoptosis was detected by TUNEL, myocardiac function was evaluated by Langendorff system. In in vitro model, adult rat cardiomyocytes were incubated with LPS (1 microg/ml) or co-incubated with calpain inhibitor-III (10 micromol/L), calpain activity, caspase-3 activity, protein levels of Bcl-2 and Bid, and cardiomyocyte apoptosis were detected.</p><p><b>RESULTS</b>in septic mice, myocardial calpain and caspase-3 activity were increased up to 2.7- and 1.8-folds, respectively. Both calpain inhibitor-III and PD150606 significantly attenuated the increase of caspase-3 activity. Myocardial protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were similar between control and septic mice, and no cleavage of both Bcl-2 and Bid was found in septic mice. Calpain inhibitor-III significantly improved myocardial function in septic mice. In in vitro model, calpain and caspase-3 activities were increased after 4 h LPS treatment, co-treatment with calpain inhibitor-III prevented caspase-3 activity increase, protein Bcl-2 and Bid were similar between normal cardiomyocytes and LPS-treated cardiomyocytes. Cardiomyocyte apoptosis was similar in in vivo and in vitro septic models.</p><p><b>CONCLUSION</b>myocardial calpain activity is increased in LPS induced septic mice, subsequent caspase-3 activation may contribute to myocardial dysfunction in septic mice without aggravating myocardial apoptosis and Bcl-2 and Bid are not involved on calpain induced caspase-3 activation in our model.</p>

Alteration of Th17 cells in mice with coxsackie virus induced myocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>to observe the alteration of T helper cells 17(Th17) in mice with acute viral myocarditis (VMC) induced by coxsackie virus B3 (CVB3), explore the role of Th17 in mice VMC.</p><p><b>METHODS</b>CVB3 or PBS was peritoneally injected to Balb/c male mice. Pathological scores were determined in hematoxylin-eosin stained sections and flow cytometric analysis was used to evaluate the frequencies of Th17 subsets in CD4(+) T cells on 7, 14, 21, 28 and 42 days after virus injection.</p><p><b>RESULTS</b>there were significant difference of the pathological scores between the VMC mice and the control ones (P < 0.05). The pathological scores of 7 d VMC subgroup were higher (1.8 ± 0.5) than those of 0 d VMC subgroup, and the scores of 14 d subgroup were highest (2.8 ± 0.4) among the six subgroup of VMC mice, and then showed a decline tendency from 21 d group. Statistical difference of the proportion of Th17 cells were seen between the VMC and controls on different time points (P < 0.05). When compared with the 0 d VMC subgroup the proportion of spleen Th17 cells increased in 7 d VMC subgroup [(2.23 ± 0.89)%], and peaked on 28 d [(5.00 ± 0.81)%]. The results of Th17 proportion were lower than those of the 28 d subgroup.</p><p><b>CONCLUSIONS</b>our data show that differentiated Th17 cells might be involved in the inflammation process of CVB3 induced VMC in mice.</p>

Treatment of femoral unstable intertrochanteric fractures in the elderly with uncemented long stem bipolar prosthetic prosthesis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of cemented long stem bipolar prosthetic prosthesis in the management of unstable intertrochanteric fractures in the elderly.</p><p><b>METHODS</b>A retrospective analysis of 23 elderly cases of uncemented long-stem prosthetic replacement for unstable intertrochanteric fractures was conducted. Of the 23 elderly patients, 6 had type IIA fracture by Evans-Jenson classification, 11 had type IIB fractures, and 6 had type III fractures.</p><p><b>RESULTS</b>One patient died due to severe respiratory failure during the follow-up period. The patients were followed up for 6 to 10 months (mean 15 months), and no dislocation, infection, loosening or sinking of the prosthesis was found in the followed-up cases with a Harris score reaching 84.8.</p><p><b>CONCLUSION</b>Cemented long-stem bipolar prosthetic prosthesis replacement is effective for management of unstable intertrochanteric fractures in the elderly.</p>

Effects of Astragalus injection in reversing left ventricular hypertrophy induced by renal hypertension in rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore whether the Astragalus injection (AI) has effect for reversing left ventricular hypertrophy and myocardial fibrosis induced by renal vascular hypertension in rats.</p><p><b>METHODS</b>Thirty male SD rats were randomized equally into three groups: the AI group, the control group and the sham-operated group. All rats, except those in the sham-operated group, were established into the hypertension models by two kidney one clip (2K1C) operation. Blood pressure was measured before operation and every 4 weeks after operation. AI intervention was given to rats in the AI group starting from the 4th week of experiment at dose of 8 g/kg by peritoneal injecting once a day for 8 weeks, while for rats in the other 2 groups, equal volume of normal saline was given instead. All rats were sacrificed 12 weeks after operation by cervical breaking. And indexes including left ventricular mass index (LVMI), left ventricular wall thickness (LVWT), inter-ventricular septal thickness (IVST), left ventricular diameter (LVD), cardiomyocytes diameter (CCD), collagen volume fraction (CVF), and peri-vascular volume collagen area (PVCA) in rats were measured.</p><p><b>RESULTS</b>Blood pressure was not different in the three groups before operation (P>0.05), whereas it rose in the control group and the AI group 4, 8 and 12 weeks after operation correspondingly, showing no difference between the two groups, but significantly higher than that in the sham-operated group (P<0.05). The related indexes in the sham-operated group, control group and AI group were: LVMI, 2.71 +/- 0.24, 3.42 +/- 0.26, 3.13 +/- 0.23, respectively; LVWT (mm), 2.25 +/- 0.42, 4.26 +/- 0.48, 3.28 +/- 0.36; IVST (mm), 2.13 +/- 0.38, 3.98 +/- 0.32, 3.02 +/- 0.28; and LVD (mm), 3.76 +/- 0.29, 2.18 +/- 0.27, 2.82 +/- 0.20 respectively. Comparisons showed that LVMI, LVWT and IVST were significantly higher, but LVD was significantly lower in the control group than those in the sham-operated group (P<0.05); LVMI, LVWT and IVST were significantly lower but LVD was significantly higher in the AI group than those in the control group (P<0.05). CCD, CVF and PVCA in the three groups (in the fore-mentioned order) were: CCD (microm), 14.54 +/- 2.25, 19.56 +/- 2.53, 16.58 +/- 2.46; CVF(%), 3.83 +/- 1.40, 11.21 +/- 2.96, 7.83 +/- 1.67; PVCA (%), 15.71 +/- 3.85, 30.58 +/- 6.25, 21.76 +/- 4.36, respectively. These indexes showed that CCD, CVF, PVCA in the control group were significantly higher than those in the sham-operated group (P<0.05); and those were significantly lower in the AI group than in the control group (P<0.05).</p><p><b>CONCLUSION</b>AI intervention can reverse the left ventricular hypertrophy and myocardial fibrosis induced by renal vascular hypertension in rats.</p>

Role of interleukin 17 in viral myocarditis and dilated cardiomyopathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of interleukin-17 (IL-17) in the evolution of viral myocarditis (VMC) into dilated cardiomyopathy (DCM).</p><p><b>METHODS</b>A mouse model of VMC was established in 100 male Balb/c mice by intraperitoneal injection of coxsackievirus B3. The expression of IL-17 protein in the cardiac tissue of the mice was detected immunohistochemically, and IL-17 mRNA in the splenocytes was examined by reverse transcription-polymerase chain reaction (RT-PCR). IL-17 levels in the plasma, peripheral blood mononuclear cell (PBMC) culture supernatants, and phytohemagglutinin (PHA)-stimulated PBMC culture supernatants were measured in 30 DCM patients, 26 non-DCM patients and 20 normal adults using enzyme-linked immunosorbent assay (ELISA), and IL-17 mRNA expression in the PBMCs was detected using RT-PCR.</p><p><b>RESULTS</b>The levels of IL-17 mRNA in the splenocytes of the mice with VMC were significantly higher at 4 and 6 weeks than those at 8 weeks (P<0.01), but not detected at 2 weeks. No IL-17 expression was found in the ventricular tissue of the mice at 2 weeks, but peaked at 4 weeks followed by gradual decrease (P<0.01). IL-17 level in PHA-stimulated PBMC culture supernatants but not the plasma, and its mRNA level in PHA-stimulated PBMCs but not the PBMC culture supernatants, were significantly elevated in DCM patients as compared with those in non-DCM patients and normal control subjects.</p><p><b>CONCLUSIONS</b>The mouse model of VMC in the chronic phase and DCM patients express high levels of IL-17, which may contribute to the transition from VMC to DCM.</p>

Comparison of peripheral blood hematopoietic progenitor cells among patients with paroxysmal, permanent atrial fibrillation or sinus rhythm / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare peripheral blood hematopoietic progenitor cells (HPCs), plasma atrial natriuretic peptide (ANP) and stromal cell-derived factor-1alpha (SDF-1alpha) among patients with paroxysmal, permanent atrial fibrillation (AF) or sinus rhythm.</p><p><b>METHODS</b>Peripheral blood concentration of CD34+HPCs were quantified by flow cytometric analysis (FCM), plasma ANP levels were measured by radioimmunoassay (RIA) method, plasma levels of SDF-1alpha were determined by enzyme linked immunosorbent assay (ELISA) in 30 patients with permanent AF, 28 patients with paroxysmal AF, and 30 patients with sinus rhythm (SR). HPCs were separated, cultured and stained for ANP by the use of alkaline phosphatase-anti-alkaline phosphatase technique (APAAP) in 30 patients (10 from each group).</p><p><b>RESULTS</b>(1) The number of CD34+HPCs in permanent AF group [(5.31 +/- 1.67) x 10(6)/L] were significantly higher comparing to paroxysmal AF group [(2.33 +/- 1.29) x 10(6)/L] (P < 0.05) and SR group [(2.03 +/- 0.64) x 10(6)/L] (P < 0.05) while CD34+HPCs was similar between paroxysmal AF group and SR group (P > 0.05). (2) Plasma levels of ANP (0.312 +/- 0.121) microg/L and SDF-1alpha (3210.2 +/- 1234.7) ng/L were also significantly higher in permanent AF group than paroxysmal AF group and SR group (all P < 0.05) and were similar in paroxysmal AF group and SR group (all P > 0.05). (3) The plasma levels of ANP and SDF-1alpha were both positive correlated with peripheral blood concentration of CD34+HPCs (r = 0.783, P < 0.01; r = 0.427, P < 0.01). (4) After 3 days of culture, ANP was weakly expressed in HPCs from patients with permanent AF but not from patients with paroxysmal AF and SR.</p><p><b>CONCLUSIONS</b>Peripheral blood HPCs together with plasma ANP and SDF-1alpha were significantly increased in patients with permanent AF. CD34+HPCs were positive correlated with the plasma levels of ANP and SDF-1alpha.</p>

Changes of Plasma Angiotensin Ⅱ and Serum Nitrogen Monoxidum Levels in Children with Congenital Heart Diseases Pre-and Post-Interventional Therapy / 实用儿科临床杂志

6.66 kPa),30 cases of light degree pulmonary artery hypertension group (3.99 kPa

Changes of Neurohormonal Level in Children with Congenital Heart Diseases at Pre-and Post-Interventional Therapy / 实用儿科临床杂志

Objective To detect neuroendocrinal factor,and explore whether neurohormonal activation exists in children with conge-nital heart disease(CHD).Methods Concentrations of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),angiotensionⅡ(AngⅡ),aldosterone(ALD),endothelin-1(ET-1),and norepinephrine(NE)were determined in 100 children with CHD and were assayed at 24 hours,1 month,3 months and 6 months after interventional therapy in 70 cases with CHD.Results Children with CHD heart disease had elevated levels of ANP(25.6?7.5) pmol/L,BNP(15.7?7.4) pmol/L,ET-1(1.12?0.31) pmol/L(all P=0.0001),(AngⅡ)(90.3?11.5) ng/L,NE(1.07?0.08) nmol/L and ALD(246.1?42.3) pmol/L(all P=0.001).There was a highly significant stepwise increase in ANP,BNP,ET-1,AngⅡ,ALD and NE according to New York Heart Association class,with even asymptomatic patients having evidence of significant neurohormonal activation.The neurohormonal function gradually returned to normal after interven-(tional) therapy.Conclusions Neurohormonal activation in children CHD bears the hallmarks of chronic heart failure,relating to symptom severity and ventricular dysfunction.