Safety factor diagnostic for tokamak core plasma from three-dimensional reconstruction of pellet ablation trail.

Using a stereo camera system, a new diagnostic for the safety factor of the core plasma based on the pellet ablation trail is applied on the Experimental Advanced Superconducting Tokamak (EAST). In EAST discharge No. 128 874, a shattered pellet injection system is applied to inject a shattered neon pellet into the EAST. Since the strong magnetic field in tokamaks binds the ablated pellet material, the orientation of the pellet ablation trail is the same as the local magnetic field direction. Thus, from the three-dimensional reconstruction result of the pellet ablation trail, the local safety factor q can be obtained. The motional Stark effect (MSE) diagnostic is applied to determine the safety factor q profile in this shot. The determined safety factor q results for this new diagnostic are in quantitative agreement with those from the MSE diagnostic with the mean relative difference of only 6.8%, confirming the effectiveness of this new diagnostic of the safety factor.

[The short-term and long-term prognostic analysis in patients with chronic total occlusion acute non-ST segment elevation myocardial infarction].

Objectives: To investigate the clinical impacts of chronic total occlusion (CTO) in acute non-ST segment elevation myocardial infarction (NSTEMI) patients underwent primary percutaneous coronary intervention (PCI). Methods: A total of 2 271 acute NSTEMI patients underwent primary PCI from China Acute Myocardial Infarction Registry were enrolled in this study and divided into the CTO group and the non-CTO group according to the angiography. The primary endpoint was in-hospital mortality and mortality during a 2-year follow-up. The secondary endpoint was major adverse cardiovascular events (MACE) including revascularization, death, re-myocardial infarction, heart failure readmission, stroke and major bleeding. Results: Thirteen-point four percent of the total acute NSTEMI patients had concurrent CTO. In-hospital mortality (3.6% vs. 1.4%, P<0.01) and 2-year mortality (9.0% vs. 5.1%, P<0.01) were significantly higher in the CTO group than those in the non-CTO group, respectively. Multiple regression analyses showed that chronic obstructive pulmonary disease (HR 7.28, 95%CI 1.50-35.35, P=0.01) was an independent risk factor of in-hospital mortality, and advanced age (HR 1.04, 95%CI 1.01-1.07, P<0.01), and low levels of ejection fraction (HR 0.95, 95%CI 0.93-0.98, P<0.01) were independent risk factors of 2-year mortality. CTO (HR1.67, 95%CI 1.10-2.54, P=0.02) was an independent risk factor of revascularization, but not a risk factor of mortality. Conclusions: Although acute NSTEMI patients concurrent with CTO had higher mortality, CTO was only an independent risk factor of revascularization, but not of mortality. Advanced age and low levels of ejection fraction were independent risk factors of long-term death among acute NSTEMI patients.

[Five-year clinical outcomes of patients with in-stent chronic total occlusion undergoing percutaneous coronary intervention].

Objective: To evaluate the safety and long-term clinical efficacy of percutaneous coronary intervention (PCI) in patients with in-stent chronic total occlusion (IS-CTO) lesions. Metheds: This is a retrospective analysis. Patients with IS-CTO who underwent PCI in Fuwai hospital from January 2010 to December 2013 were enrolled. A total of 212 patients who met the inclusion criteria were included in the IS-CTO group, 212 matched patients with primary CTO lesions were included in the de novo CTO group. The incidence of complications and the success rate of PCI were compared between the two groups. Successful PCI was defined as successfully implantation of stent(s) at target CTO lesions. The primary endpoint was defined as a composite event of cardiac death and myocardial infarction (MI). Secondary endpoints including PCI success, all-cause death, cardiac death, MI, target vessel related MI, revascularization, target vessel revascularization, heart failure for rehospitalization. The patients were followed up for 5 years after PCI. Results: A total of 424 cases were included. The mean age was (57.8±10.5) years, there were 364 males in this cohort. The left ventricular ejection fraction was significantly lower ((58.7±9.2)% vs. (61.0±7.7)%, P=0.01) and the SYNTAX scores was significantly higher (19.4±8.3 vs. 15.3±10.0, P<0.01) in IS-CTO group than that in de novo CTO group. The proportion of patients with target CTO lesions in left anterior descending artery was significantly higher (42.9% (50/212) vs. 23.6% (91/212), P<0.01) in IS-CTO group than that in de novo CTO group. The rate of successful PCI (71.7% (152/212) vs. 69.8% (148/212), P=0.70) and complication (40.6% (86/212) vs. 36.3% (77/212), P=0.37) was similar between the two groups. The incidence of primary endpoint at 5 years was significantly higher in IS-CTO group (10.8% (23/212) vs. 4.7% (10/212), P=0.02), which was driven by higher incidence of MI (9.0% (19/212) vs. 4.2% (9/212), P=0.05). There were a trend of higher secondary endpoints in IS-CTO group (all P>0.05). Conclusion: The safety and effectiveness of PCI are acceptable in patients with IS-CTO, but the risk of long-term cardiac death and MI is higher among patients with IS-CTO as compared to patients with primary CTO lesions.

[The acute and long-term outcome of patients with ST segment elevation myocardial infarction concurrent with chronic total occlusion].

Objective: To evaluate the acute and long-term outcome of patients with ST segment elevation myocardial infarction (STEMI) concurrent with chronic total occlusion (CTO) undergoing primary percutaneous coronary intervention (PCI). Methods: 11 905 STEMI patients from the China Acute Myocardial Infarction Registry were enrolled in this study and divided into CTO group and non-CTO group according to the angiography results of primary PCI. 1∶3 propensity score matching was used to match the patients between the two groups. The primary endpoint was in-hospital mortality and mortality at 1-year post PCI. The secondary endpoint was major adverse cardiovascular events (MACE) including death, re-myocardial infarction, revascularization, heart failure associated readmission, stroke and major bleeding at 1-year post PCI. Results: There were 931 CTO patients (7.8%) in this cohort (male=755 (81.1%), mean age (62.2±11.4 years)). The rest 10 974 patients were STEMI without CTO (male=8 829 (80.5%),mean age (60.0±11.8) years). After propensity score matching, 896 patients were enrolled in CTO group and 2 688 in non-CTO group. In-hospital mortality was significantly higher in the CTO group than in non-CTO group (4.2% vs. 2.4%, P=0.006). The ratio of all cause death, cardiac death, and MACE at 1-year follow up was also significantly higher in the CTO group than in non-CTO group (8.5% vs. 4.4%, P<0.001, 5.3% vs. 2.6%, P=0.001, 35.1% vs. 23.3%, P<0.001, respectively). Multiple regression analysis showed that CTO (HR=1.54, 95%CI 1.06-2.22, P=0.022), advanced age (HR=1.06, 95%CI 1.04-1.08, P<0.001), and previous heart failure history (HR=4.10, 95%CI 1.90-8.83, P<0.001) were independent risk factors of 1-year mortality. Conclusions: The in-hospital and 1-year mortality increased significantly in STEMI patients concurrent with CTO. CTO, advanced age and history of heart failure are independent risk factors of 1-year death among STEMI patients.

[Role and related mechanism of Mst-1 on regulating hypoxic reoxygenation induced autophagy and apoptosis in cardiomyocytes of mouse].

Objective: To explore the role and related mechanism of mammalian sterile 20-like kinase 1(Mst-1)in regulating hypoxia reoxygenation (HR) induced myocardial cell autophagy and apoptosis. Methods: Enzyme digestion method combined with differential adherent method was used to culture neonatal mouse myocardial cells. HR model was established by hypoxia for 24 hours and reoxygenation for 6 hours. The experimental groups including control group (normal cultured cardiomyocytes), Mst-1 empty virus group (cardiomyocytes transfected with recombinant lentiviral empty vector for 48 hours), Mst-1 knockdown group (recombinant lentivirus carrying Mst-1small interfering RNA (siRNA) was transfected into cardiomyocytes for 48 hours), Mst-1 overexpression group (cardiomyocytes were transfected with recombinant lentivirus carrying Mst-1 gene for 48 hours), HR group (cardiomyocytes exposed to HR), Mst-1 knockdown+HR group (HR model of cardiomyocyte was established 48 hours after transfection with recombinant lentivirus carrying Mst-1siRNA) and Mst-1 overexpression+HR group (HR model of cardiomyocyte was established 48 hours after transfection with recombinant lentivirus carrying Mst-1 gene). Real-time fluorescence quantitative RCR (qPCR) and Western blot were used to detect the relative expression of Mst-1 mRNA and protein in the cells, immunofluorescence staining was used to detect cardiomyocyte troponin T (cTnT), and autophagosomes and autophagy enzyme changes. TUNEL method was used to detect myocardial cell apoptosis, Western blot was adopted to detect autophagy-related protein microtubule-related protein 1 light chain 3 (LC3) Ⅱ/LC3 Ⅰ, P62 and apoptosis-related protein cleaved-caspase 9, pro-caspase 9, cleaved-caspase-3, pro-caspase-3, and myeloid leukemia 1 (MCL-1) expression. MCL-1 inhibitor A1210477 was used to validate the signaling pathway of Mst-1 on regulating cardiomyocyte apoptosis and autophagy. Results: Immunofluorescence detection revealed that the cultured cells expressed cardiomyocyte-specific marker cTnT. The expression of Mst-1 in cardiomyocytes increased in HR model. Lentiviral transfection could effectively inhibit or overexpress Mst-1 in treated cells. The levels of autophagosomes and autophagolysosomes in cardiomyocytes undergoing HR and in Mst-1 overexpression+HR group were lower than those of control group, while autophagosomes and autophagolysosomes in cardiomyocytes of Mst-1 knockdown+HR group was significantly higher than in the HR group (all P<0.05). The TUNEL results showed that the proportion of TUNEL positive cells was significantly increased in the HR group and Mst-1 overexpression+HR group than in the control group, while the proportion of TUNEL positive cells was significantly decreased in the Mst-1 knockdown group+HR group as compared to the HR group (all P<0.05). Western blot results showed that the LC3 Ⅱ/LC3 Ⅰ levels were significantly lower, while the expression levels of P62, cleaved-caspase-9 and cleaved-caspase-3 were significantly higher in the HR group and Mst-1 overexpression+HR group than in control group (all P<0.05). The LC3 Ⅱ/LC3 Ⅰ value was significantly higher, and the expression levels of P62, cleaved-caspase-9 and cleaved-caspase-3 were significantly lower in the Mst-1 knockdown+HR group than in the HR group (P both<0.05). The expression level of P-MCL-1 protein was significantly lower in cardiomyocytes of HR and Mst-1 overexpression+HR group than in control group, and the expression level of P-MCL-1 protein was higher in Mst-1 knockdown+HR group than in HR group (P both<0.05). The recovery experiment showed that inhibiting MCL-1 in cells can block the regulatory effect of Mst-1 siRNA on cell autophagy and apoptosis. Conclusion: Inhibiting Mst-1 expression in cardiomyocytes can promote the autophagy of cardiomyocytes induced by hypoxic reoxygenation and reduce the apoptosis of cardiomyocytes via activating McL-1.

[Clinical features of patients with hypertrophic obstructive cardiomyopathy combining obstructive sleep apnea].

Objective: To investigate the clinical features of patients with hypertrophic obstructive cardiomyopathy (HOCM) combined with obstructive sleep apnea (OSA). Methods: From 2010 to 2018, a total of 299 patients who were diagnosed with hypertrophic cardiomyopathy and underwent sleep monitoring at Fuwai Hospital were retrospectively analyzed. General clinical features, data of echocardiography, and sleep breathing parameters were recorded. OSA was diagnosed by apnea-hypopnea index ≥ 5 events/hour. Clinical characteristics were compared between patients with and without OSA. Results: A total of 156 (52.2%) HOCM patients were diagnosed with OSA. Compared with patients without OSA, patients with OSA were older((54±10) years vs (45±14) years, P<0.001), had a higher body mass index ((27±3) kg/m(2) vs (25±3) kg/m(2), P<0.001), a higher prevalence of hypertension (54.4% (85/156) vs 21.0% (30/143), P<0.001), hyperlipidemia (37.2% (58/156) vs 13.3% (19/143), P<0.001) and smoking history (48.1% (75/156) vs 35.0% (50/143), P=0.022). Patients with OSA also had a higher incidence of New York Heart Association functional class Ⅱ or Ⅲ (P=0.017), atrial fibrillation (P=0.005), and higher levels of systolic and diastolic blood pressure, fast glucose and high-sensitive c-reactive protein (all P<0.001). Left ventricular end-diastolic diameter as well as ascending aorta diameter in patients with OSA were also greater than those without OSA (both P<0.001). Apnea-hypopnea index (AHI) value positively correlated with left ventricular end-diastolic diameter (r=0.346), ascending aorta diameter (r=0.357) and high-sensitive c-reactive protein (r=0.230) (all P<0.001). Conclusions: A high prevalence of OSA occurs in patients with HOCM. Severity of OSA correlates with cardiac remodeling and serum inflammatory factor level. As for HOCM patients, clinicians should actively monitor the sleep breathing parameters in order to recognize and treat potential OSA, thereby improving the prognosis of patients with HOCM.

[Gender difference in efficacy of intra-aortic balloon pump in acute myocardial infarction patients complicating with cardiogenic shock].

Objective: To investigate the effect of gender on the efficacy of intra-aortic balloon pump(IABP) applied in patients with cardiogenic shock complicated by acute myocardial infarction(AMI). Methods: A total of 209 patients diagnosed as cardiogenic shock complicated by AMI admitted in Fuwai Hospital from June 2012 to May 2018 were enrolled in our study. We collected the data from medical records and investigated their clinical manifestation and laboratory examination and IABP support, as well as 28-day (from diagnosis of cardiogenic shock) mortality retrospectively. Kaplan-Meier survival analysis was used to compare the 28-day survival rates of patients of different genders/with or without IABP treatment. Adjustment for age, systolic blood pressure, ST segment elevation myocardial infarction, dual antiplatelet, coma, APACHEⅡ score and SAPSⅡ score, Cox regression analysis was used to detect the affect of IABP treatment on the risk of all-cause mortality in different crowd, and using Z test to evaluate the modification effect of gender on IABP treatment efficacy. Results: A total of 209 patients were included in this study, with 148 males (80 (54.05%) cases received IABP support) and 61 females (22 (36.06%) cases received IABP support). A total of 102 patients received IABP treatment. The 28-day survival rate of male patients was higher than that of females (39.2% (58/148) vs. 26.2% (16/61), Log-rank P=0.034). The 28-day survival rate of patients receiving IABP was significantly higher than that of non-IABP groups (46.1% (47/102) vs. 25.2% (27/107), Log-rank P=0.001 7). Among female patients, there was no statistically significant difference in 28-day survival rate between those who received IABP and those who did not receive IABP (P=0.889). While in male patients, the 28-day survival rate of those who received IABP was higher than that of those who did not receive IABP (51.2% (41/80) vs. 25.0% (17/68), P=0.001). The survival rate of male patients treated with IABP was higher than that of male patients who did not receive IABP, female patients who did not receive IABP and female patients who received IABP (all P<0.05). After multiple regression analysis and adjustment of confounding factors, it was found that IABP implantation can significantly reduce the 28-day mortality risk in male patients (HR=0.44, 95%CI 0.25-0.77 P=0.004). While it had no inpact on the death risk in female patients(P= 0.401). The impact of IABP implantation in patients of different genders was significantly different (Z=-2.32, P=0.020). Conclusion: In AMI patients complicating cardiogenic shock, there is a gender difference in the impact of IABP implantation on the 28-day mortality risk, and protective effects are seen only in men.

[Impact of type 2 diabetes mellitus on the progression and revascularization of coronary non-target lesions in patients with coronary heart disease].

Objective: To investigate the impact of type 2 diabetes mellitus on progression and revascularization of coronary non-target lesions in patients with coronary heart disease. Methods: From January 2010 to September 2014, we retrospectively analyzed the clinical data of patients with coronary heart disease who underwent two consecutive coronary angiographies at Fuwai Hospital. At least one coronary non-target lesion was recorded at the first procedure in these patients. Patients were grouped according to the diagnose of type 2 diabetes mellitus. Demographic features, risk factors of coronary heart disease, laboratory results as well as characteristics of coronary non-target lesions were collected at baseline (first coronary angiography) and follow-up (second coronary angiography). Lesion progression was defined by quantitative coronary angiography analysis. Lesions revascularization was recorded. Multivariable Cox regression analysis was used to define the impacts of diabetes mellitus on progression and revascularization of non-target lesions. Subgroup analysis in diabetic and non-diabetic groups were further performed. Receiver operating characteristics curve was used to identify the predictive value of HbA1c. Results: A total of 1 255 patients were included, and 1 003(79.9%) were male, age was(58.0±9.7) years old. And 486 patients were diagnosed with type 2 diabetes mellitus. Follow-up time was (14.8±4.5) months. Compared with non-diabetic group, diabetic group were older with less male and had higher BMI index as well as higher prevalence of hypertension, dyslipidemia, prior myocardial infarction and prior percutaneous coronary intervention(all P<0.05). Diabetic patients also had higher level of white blood cells, erythrocyte sedimentation rate, C-reactive protein, endothelin and HbA1c at both baseline and follow-up compared with non-diabetic patients (all P<0.01). There was no significant difference on progression of non-target lesions (20.0%(97/486) vs. 18.5%(142/769), P=0.512), revascularization of non-target lesions (13.2%(64/486) vs. 15.9%(122/769), P=0.190) and non-target lesion related myocardial infarction(1.9%(9/486) vs. 1.3%(10/769), P=0.436) between diabetic and non-diabetic patients. Multivariable Cox regression analysis revealed that diabetes mellitus was not an independent predictor for progression and revascularization of non-target lesions (Both P>0.05). Subgroup analysis in diabetic patients showed that baseline HbA1c level(HR=1.160, 95%CI 1.009-1.333, P=0.037) was an independent predictor for non-target lesion progression. Cut-off value of HbA1c was 6.5% (Area Under Curve(AUC) 0.57, specificity 88.7%; sensitivity 24.2%, P=0.046) by receiver operating characteristics curve. Patients with HbA1c level above 6.5% had 2.8 times higher risk of lesion progression compared with patients with HbA1c level below 6.5% (HR=2.838, 95%CI 1.505-5.349, P=0.001). Compared with non-diabetic patients, diabetic patients with HbA1c below 6.5% also had lower risk of lesion progression (HR=0.469, 95%CI 0.252-0.872, P=0.012). ST-segment elevated myocardial infarction was an independent predictor for revascularization of non-target lesions in diabetic patients. Conclusion: Type 2 diabetes mellitus is not an independent predictor for progression and revascularization of coronary non-target lesions in patients with coronary heart disease. However, elevated HbA1c level is a risk factor for progression of non-target lesion in patients with type 2 diabetes mellitus.

[Prognostic value of SYNTAX score on 1 year outcome in patients underwent percutaneous coronary intervention].

Objective: To investigate the prognostic value of SYNTAX score on 1 year outcome in coronary heart disease patients underwent percutaneous coronary intervention(PCI). Methods: The present study (PANDA Ⅲ trial) was a perspective, multi-center, randomized controlled trial. Between December 2013 and August 2014, 2 348 patients who underwent PCI from 46 centers were enrolled. SYNTAX score was calculated from all patients. Patients were divided into 3 groups based on SYNTAX score: lower risk group (SYNTAX score≤22, 1 777 patients), intermediate risk group (SYNTAX score 23-32, 412 patients), and higher risk group (SYNTAX score≥33, 159 patients). The patients were followed up after the procedure for one year.Primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction,and ischemia driven target lesion revascularization. Secondary endpoints included stent thrombosis and major adverse cardiac events were defined as a composite of all-cause death, myocardial infarction and any revascularization. Results: (1) A total of 1 766 (99.2%), 411 (99.8%),and 159 (100%) patients in the lower risk group, intermediate risk and higher risk group completed the 1 year follow up. (2) Incidence of TLF were 5.6%(99/1 763) in lower risk group, 8.8%(36/411) in intermediate risk group,and 8.8%(14/159) in higher risk group(P=0.03). The incidence of target vessel myocardial infarction in lower risk group was 3.9%(68/1 763), 6.6%(27/411) in intermediate risk group,and 7.5% (12/159) in higher risk group(P=0.01).Prevalence of cardiac death and ischemia driven target lesion revascularization was similar among the 3 groups(P>0.05).(3) The probable stent thrombosis events rate was 0.1% (1/1 763), 0.7% (3/411), and 0.6% (1/159) in the lower, intermediate,and higher risk groups respectively (P=0.02). The incidence of major adverse cardiac events was 8.1% (142/1 763) in lower-risk group, 11.7% (48/411) in intermediate risk group, and 14.5% (23/159) in higher risk group (P<0.01). The incidence of all-cause death was 1.7%(30/1 763) in lower-risk group, 1.7%(7/411) in intermediate risk group, and 6.3%(10/159)in higher risk group (P<0.01). The incidence of myocardial infarction was 4.2% (74/1 763) in lower-risk group, 6.6% (27/411) in intermediate risk group, and 8.2% (13/159) in higher risk group(P=0.02).Incidence of any revascularization was similar among groups(P=0.59). (4) The multivariable Cox analysis showed that age (HR=1.04, 95%CI 1.02-1.06, P<0.01), total implanted stent length (HR=1.01, 95%CI 1.00-1.02, P=0.03), and baseline SYNTAX score (HR=1.02, 95%CI 1.02-1.04, P=0.02) were independent risk factors of TLF after PCI in this patient cohort. Conclusion: The SYNTAX score is a valuable tool for predicting prognosis on 1 year in coronary heart disease patients underwent PCI. Trial Registration www.clinicaltrials.gov, NCT02017275.

[Efficacy of bare metal stent for treating focal coronary artery aneurysm complicating with severe stenosis in single coronary artery].

Objective: To investigate the efficacy of bare metal stent for treating focal coronary artery aneurysm complicating with severe stenosisin single coronary artery. Methods: This retrospective analysis was performed in 7 patients who were diagnosed as local coronary artery aneurysm complicating with severe stenosis(≥70%) in single coronary artery and treated with bare metal stent during the period from December 2012 to June 2015 in Fuwai Hospital. All 7 patients were male with age of (62±11) years old. During the interventional operation, the narrow parts were pre-expanded,and all patients received bare metal stents implantation to cover aneurysms.The clinical and imaging data of patients immediately post procedure and at postoperative follow-up were collected to evaluate the clinical efficacy. Results: There were 5 cases of left anterior descending aneurysms and 2 cases of right coronary artery aneurysms. The diameter of aneurysm was (5.21±1.28)mm, and the length was (13.71±3.88)mm. There was intracranial vortex in coronary arteriography immediately after intervention.Proximalstenosis of coronary artery aneurysm was disappeared,and the distal blood flow was TIMI class 3.There were no signs of aortic dissection and thrombus formation.During 6(6 16) months follow-up, the aneurysms were disappeared,and there were no major adverse cardiovascular events which including myocardial ischemia, acute myocardial infarction, revascularization,bleeding,and death for all patients. Conclusion: Initial experience shows that double-layer bare metal stents implantation for patients with localized coronary artery aneurysm complicating with severe stenosis in single vessel is safe and effective.

[Long-term outcome and related predictors of alcohol septal ablation for patients with hypertrophic obstructive cardiomyopathy].

Objective: To observe the long-term prognosis and related outcome predictors for hypertrophic obstructive cadiomyopathy (HOCM) patients underwent alcohol septal ablation (ASA). Methods: A total of 227 consecutive patients(age: (47.8±11.7) years) treated by ASA from September 2005 to December 2013 in our hospital were included and followed-up for 4.42 years(range: ( 1.17-9.93) years). Follow up rate is 97.4%(221/227). General information, medical history, data of ASA and complications during hospitalization were obtained through access to medical records of patients. The patients were followed up by telephone or outpatient visit. Results: During hospitalization period, one patient died due to retroperitoneal hemorrhage, two ventricular fibrillation events and two sustained ventricular tachycardia events occurred and all patients were successfully recovered after electrical cardioversion (defibrillation). Four cardiac tamponade events occurred, 35.7% (81/227) patients experienced temporary three degree atrioventricular block. Five delayed three degree atrioventricular block evens occurred. During follow up, the percent of NYHA Ⅲ/Ⅳclass was significantly reduced (10.1%(23/227)vs. 74.9%(170/227), P=0.000). The incidence of syncope and amaurosis fugax was also reduced(2.6% (6/227) vs. 39.2% (89/227), P=0.035). A total of six patients died (4 cardiac death), one patient complicating atrial fibrillation died of cerebral embolism, one patient died of rectal cancer. One cerebral hemorrhage occurred. Six patients developed-new onset atrial fibrillation. One patient received permanent pacemaker implantation. Eight patients received surgical myocardial resection. Three patients underwent repeated ASA. Survival free of all-cause mortality at 1, 5, 9 year was 100%, 96%, 96%, respectively. Survival free of cardiac death and NYHA Ⅲ/Ⅳclass at 1, 5, 9 year was 100%, 86%, 70%, respectively. Cox-regression analysis showed that residual left ventricular outflow tract gradient after ablation(HR=1.027, 95%CI 1.006-1.048, P=0.010), less volume of injected ethanol(HR=0.596, 95%CI 0.398-0.892, P=0.012), presence of temporary complete atrioventricular block (HR=0.332, 95%CI 0.124-0.886, P=0.028)were independent predictors of cardiac death and NYHA Ⅲ/Ⅳ. Conclusion: Our study results suggest that ASA could significantly improve symptoms and outcome in patients with HOCM. Residual left ventricular outflow tract gradient after ablation, less volume of injected ethanol, presence of temporary complete atrioventricular block during ASA are independent predictors of cardiac death and NYHA Ⅲ/Ⅳ.

Dominant-negative Ikaros cooperates with BCR-ABL1 to induce human acute myeloid leukemia in xenografts.

Historically, our understanding of mechanisms underlying human leukemogenesis are inferred from genetically engineered mouse models. Relatively, few models that use primary human cells recapitulate the full leukemic transformation as assayed in xenografts and myeloid transformation is infrequent. We report a humanized experimental leukemia model where xenografts develop aggressive acute myeloid leukemia (AML) with disseminated myeloid sarcomas within 4 weeks following transplantation of cord blood transduced with vectors expressing BCR-ABL1 and a dominant-negative isoform of IKAROS, Ik6. Ik6 induced transcriptional programs in BCR-ABL1-transduced progenitors that contained repressed B-cell progenitor programs, along with strong stemness, proliferation and granulocyte-monocytic progenitor (GMP) signatures-a novel combination not induced in control groups. Thus, wild-type IKAROS restrains stemness properties and has tumor suppressor activity in BCR-ABL1-initiated leukemia. Although IKAROS mutations/deletions are common in lymphoid transformation, they are found also at low frequency in AML that progress from a prior myeloproliferative neoplasm (MPN) state. Our experimental system provides an excellent model to gain insight into these rare cases of AML transformation and the properties conferred by IKAROS loss of function as a secondary mutation. More generally, our data points to the importance of deregulated stemness/lineage commitment programs in human myeloid leukemogenesis.

Visfatin stimulates production of monocyte chemotactic protein-1 and interleukin-6 in human vein umbilical endothelial cells.

Monocyte chemotactic protein-1 and interleukin-6 are important inflammatory cytokines, which have close relationships with atherosclerosis. Visfatin is a novel adipokine involved in regulation of inflammatory cytokines, however, associations of visfatin with cytokines (MCP-1, IL-6) in human umbilical vein endothelial cells are unclear. The aim of this study was to determine whether visfatin has effects on the expression of MCP-1 and IL-6 in human umbilical vein endothelial cells. Enzyme-linked immunosorbent assay were used for measuring MCP-1 and IL-6 production in human umbilical vein endothelial cells. Real-time quantitative reverse-transcription polymerase chain reaction was used for determining MCP-1 and IL-6 mRNA expression. For the pathway determination following inhibitors were used: wortmannin [phosphatiylinositol 3-kinase (PI3K)], SB203580 [p38 mitogen-activated protein kinase (MAPK)], PD98059 [extracellular signal-regulated kinase (ERK) 1/2)], JNK inhibitor II [c-Jun NH 2-terminal kinase (JNK)]. We demonstrated that visfatin could obviously upregulate secretion of MCP-1and IL-6 in a dose- and time-dependent manner in human umbilical vein endothelial cells. Visfatin-induced effects were diminished by SB203580, wortmannin, and PD98059. In summary, these results suggest that visfatin-induced MCP-1 and IL-6 production involve p38 MAPK, PI3K, and ERK 1/2 pathways in human umbilical vein endothelial cells as determined by inhibition with specific inhibitors.

Gene expression analysis in soybean in response to the causal agent of Asian soybean rust (Phakopsora pachyrhizi Sydow) in an early growth stage.

Asian soybean rust (ASR) caused by Phakopsora pachyrhizi Sydow is a potentially devastating disease posing a serious threat to the soybean industry. Understanding plant host response at the molecular level is certainly important for control of the disease. The main objective of this study was to perform a transcriptome profiling of P. pachyrhizi-exposed young soybean plants (V2 growth stage) using whole genome Affymetrix microarrays of soybean. Three-week-old soybean cv. 5601 T plants at the V2 growth stage were inoculated with P. pachyrhizi, and leaf samples were collected 72 h post inoculation with subsequent microarray analysis performed. A total of 112 genes were found to be differentially expressed from P. pachyrhizi exposure, of which 46 were upregulated, and 66 were downregulated. Most of the differentially expressed genes were general defense and stress-related genes, and 34 of these were unknown. Confirmational real-time reverse transcription-polymerase chain reaction was performed on a subset of 5 out of 112 differentially expressed genes. These results were congruent with the microarray analysis. Our results indicated that low and nonspecific innate response to the pathogen may account for the failure to develop rust resistance in the soybean variety studied. To our knowledge, this is the first microarray analysis of soybean in response to ASR.

Notch signaling in development and disease.

Notch receptors and ligands were first identified in flies and worms, where they were shown to regulate cell proliferation, cell differentiation, and, in particular, binary cell fate decisions in a variety of developmental contexts. The first mammalian Notch homolog was discovered to be a partner in a chromosomal translocation in a subset of human T-cell leukemias. Subsequent studies in mice and humans have shown that Notch signaling plays essential roles at multiple stages of hematopoiesis, and also regulates the development or homeostasis of cells in many tissues and organs. Thus, it is not surprising that mutations which disrupt Notch signaling cause a wide range of cancers and developmental disorders. Perhaps because it is so widely used, Notch signaling is subject to many unusual forms of regulation. In this review, we will first outline key aspects of Notch signaling and its regulation by endocytosis, glycosylation, and ubiquitination. We will then overview recent literature elucidating how Notch regulates cell-lineage decisions in a variety of developmental contexts. Finally, we will describe the roles of dysregulated Notch signaling in causing several types of cancer and other pathologies.

[Study on mechanism of eye-signs in blood stasis syndrome].

Through a study of 504 cases of observation group with eye-signs in blood stasis syndrome (BSS) and 112 cases of control group without eye-signs in BSS, it has been found that in the observation group, the scores of the blood concentration, viscosity, aggregability and coagulability, level of plasma thromboxane B2 (TXB2), and the ratio of TXB2/6-keto-PGF1 alpha were obviously higher than those in the control group, but level of 6-keto-PGF1 alpha was obviously lower than that in the control group; the above-mentioned parameters of blood hyperviscosity syndrome, was obviously higher than that in the control group (90.08%:2.68%); comparisons between the two groups were significantly different (P < 0.001). Certain findings of the pathological base of eye-signs in BSS were found in the investigations.

Soluble CD44 isoforms in serum as potential markers of metastatic gastric carcinoma.

A splice variant of CD44 (exon V4-V7) confers metastatic behavior in a rat carcinoma model; aberrant expression of splice variants has been detected on a variety of human tumor cell lines as well as primary and metastatic human tumors, including lymphomas, carcinomas (colon, thyroid, mamma, bladder), and glioma. We used enzyme-linked immunosorbent assay to determine the concentration of soluble CD44 in the serum samples of 10 normal individuals and 41 patients with various stages of gastric cancer. Soluble CD44S and its isoforms, V5 and V6, were present in the serum of normal individuals (288.53 +/- 18.33, 25.49 +/- 1.70, and 148.32 +/- 3.15 ng/ml, respectively). The concentrations of soluble CD44 V5 and V6 were elevated in patients with advanced gastric carcinoma (69.39 +/- 6.06 and 216.62 +/- 32.98 ng/ml, respectively). Serum CD44 V5 concentrations correlated with the extent of tumor invasion (T), the status of lymph node involvement (N), and distant metastasis (M) (TNM staging) (p < 0.05), whereas CD44S did not. These results suggest that detection of abnormal regulation of CD44 splicing could be helpful in gastric cancer diagnosis and disease evaluation.

[Comparative study of diagnostic standards of eye-signs in blood stasis syndrome and of blood stasis syndrome].

By virtue of a diagnostic study of 781 cases on the basis of six standards, it was shown that for the effectiveness in diagnostic positive rate, sensitivity, specificity, false positive rate, false negative rate and comprehensive scoring, the International Diagnostic Standards for Blood Stasis Syndrome (BSS) and Chinese Diagnostic Standards for BSS were the best ones, BSS Eye-Signs and Japanese BSS Diagnostic Standards were the second, trial program of International Stasis Diagnostic Standards and Zhongshan's BSS tenderness points came the third. Each standard has its unique advantage and therefore, we should take the other's advantage to offset one's weakness. The causes of their weakness have been discussed and the rational recommendation for their application has been proposed.