Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

BACKGROUNDThe plasma cystatin C concentration (PcyC) has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions.

METHODSOne hundred and thirty consecutive patients with borderline coronary lesions (40% to 60% isolated single stenosis assessed by quantitative coronary angiography) were enrolled into the borderline coronary lesion (BCL) group, and one hundred and thirty-six subjects without coronary lesions comprised the controls (CTR). The subjects in the BCL group were randomized into routine treatment (RTT, n = 60), and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n = 70), both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography.

RESULTSPcyC levels were significantly higher in the BCL group than in the CTR group; (2003.26 ± 825.73) ng/ml vs. (1897.83 ± 664.46) ng/ml (P < 0.01). Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group (P < 0.05). Moreover, there was a trend towards a slight decrease in the RTT patients, (54.38 ± 10.67)% vs. (50.29 ± 9.89)% (P > 0.05), and a significant decrease in the CBT patients, (53.65 ± 9.48%) vs. (40.38 ± 12.93)% (P < 0.05), in the mean percent stenosis of borderline coronary lesions before and after six months of treatment.

CONCLUSIONSCystatin C played an important role in the development of coronary artery disease, and was associated with the severity of coronary lesions. The combination of atorvastatin and probucol decreased PcyC levels, and could be the treatment of choice.

Aged ; Anticholesteremic Agents ; therapeutic use ; Atorvastatin Calcium ; Coronary Disease ; blood ; drug therapy ; pathology ; Cystatin C ; blood ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Male ; Middle Aged ; Probucol ; therapeutic use ; Prospective Studies ; Pyrroles ; therapeutic use

BACKGROUNDThe optimal revascularization strategy in patients with heart failure with preserved ejection fraction (HFPEF) remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with HFPEF.

METHODSFrom July 2003 through September 2005, a total of 920 patients with coronary artery disease (CAD) and HFPEF (ejection fraction ≥ 50%) underwent PCI (n = 350) or CABG (n = 570). We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events (MACCE), including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days.

RESULTSIn-hospital mortality was significantly lower in the PCI group than in the CABG group (0.3% vs. 2.5%, adjusted P = 0.016). During follow-up, there was no significant difference in the two groups with regard to mortality rates (2.3% vs. 3.5%, adjusted P = 0.423). Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG (13.4% vs. 4.0%, adjusted P < 0.001), mainly due to higher rate of repeat revascularization (adjusted P < 0.001). Independent predictors of mortality were age, New York Heart Association (NYHA) class and chronic total occlusion.

CONCLUSIONAmong patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.

Aged ; Angioplasty, Balloon, Coronary ; mortality ; Coronary Artery Bypass ; mortality ; Female ; Heart Failure ; physiopathology ; therapy ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Stents

BACKGROUNDIt has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial. This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes.

METHODSThe β-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed.

RESULTSThe ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95 ± 2.41) U/g or (29.28 ± 3.65) U/g vs. (0.84 ± 0.21) U/g, P < 0.01), and ultrasonic destruction PESDA resulted in more significant gene expression than ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced β-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35 ± 11.21) U/g protein vs. (14.13 ± 2.58) U/g protein, P < 0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63 ± 7.65) U/g vs. (14.13 ± 2.58) U/g, P < 0.05).

CONCLUSIONSUltrasonic destruction of microbubbles might be a promising method for the delivery of non-viral DNA into cardiac myocytes, and the gene tranfection is related to the characteristics of microbubbles.

Albumins ; Animals ; Cell Survival ; genetics ; physiology ; Cells, Cultured ; Microbubbles ; Myocytes, Cardiac ; cytology ; metabolism ; Rats ; Rats, Wistar ; Transfection ; methods ; Ultrasonics ; methods ; beta-Galactosidase ; genetics ; metabolism

BACKGROUNDIn patients with chronic total occlusion (CTO) and multivessel coronary artery disease, the comparison of surgical and the percutaneous revascularization strategies has rarely been conducted. The aim of this study was to compare long term clinical outcomes of drug eluting stent (DES) implantation with coronary artery bypass surgery (CABG) in the patients with CTO and multivessel disease.

METHODSFrom a prospective registry of 6000 patients in our institution, we included patients with CTO and multivessel coronary artery disease who underwent either CABG (n = 679) or DES (n = 267) treatment. Their propensity risk score was used for adjusting baseline differences.

RESULTSAt a median follow-up of three years, propensity score adjusted Cox regression analysis showed that the rate of major adverse cardiac cerebrovascular events (MACCE) was lower in CABG group (12.7% vs. 24.3%, hazard ratio (HR) 1.969, 95%CI 1.219 - 3.179, P = 0.006) mainly due to lower rate of target vessel revascularization in CABG group than in DES group (3.1% vs. 17.2%, HR 16.14, 95%CI 5.739 - 45.391, P < 0.001). The incidence of cardiac death or myocardial infarction (composite end point) was not significantly different between these two groups. On multivariate analysis, the significant predictors of MACCE were only the type of revascularization. Age, left ventricular ejection fraction (LVEF), and complete revascularization were identified as significant predictors of composite end points.

CONCLUSIONSOur study shows that in patients with CTO and multivessel coronary disease, DES can offer comparable long term outcomes in cardiac death and myocardial infraction free survival in comparison with CABG. However, there is an increased rate of MACCE which results from more repeat revascularizations. Obtaining a complete revascularization is crucial for decreasing adverse cardiac events.

Angioplasty, Balloon, Coronary ; methods ; Chronic Disease ; Coronary Angiography ; Coronary Artery Bypass ; methods ; Coronary Artery Disease ; surgery ; therapy ; Coronary Occlusion ; surgery ; therapy ; Drug-Eluting Stents ; Humans ; Prospective Studies

BACKGROUNDAvailable drug-eluting stents (DES) have achieved great success in reducing restenosis rates. Recently, investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid (PLGA) polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.

METHODSA prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients (TIVOLI group: 168 patients; ENDEAVOR group: 156 patients) at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions (lesion length ≤ 40 mm, reference vessel diameter 2.25-4.00 mm). The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years, including major adverse cardiac events (cardiac death, myocardial infarction, or target-lesion revascularization) and stent thrombosis.

RESULTSAngiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group (in-stent (0.25 ± 0.33) mm vs. (0.57 ± 0.55) mm, diff (95%CI) -0.23 (-0.32, -0.14), P < 0.0001; in-segment (0.25 ± 0.33) mm vs. (0.42 ± 0.55) mm, diff (95%CI) -0.13 (-0.23, -0.02), P = 0.0083). The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group (P = 0.0229). Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization (4.2% vs. 9.6%, P = 0.0495) at 2 years. The two-year major adverse cardiac events (MACE) rate was lower for the TIVOLI group, but not significantly different (6.6% vs. 10.9%, P = 0.1630).

CONCLUSIONSTIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization (TLR) at 2 years. The MACE rate at 2 years was comparable in both groups.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Artery Disease ; drug therapy ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Polymers ; chemistry ; Sirolimus ; analogs & derivatives ; therapeutic use ; Treatment Outcome

BACKGROUNDThe Syntax score was recently developed as a comprehensive, angiographic tool grading the complexity of coronary artery disease (CAD). It aims to assist in patient selection and risk stratification of patients with extensive CAD undergoing revascularization. However, the prognostic value of the Syntax score in patients undergoing percutaneous coronary intervention (PCI) has not been validated. The aim of this study was to evaluate its role in predicting long-term incidences of major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing PCI for 3-vessel disease.

METHODSTwo hundred and three consecutive patients with de novo 3-vessel CAD undergoing PCI with sirolimus-eluting stents were studied. Their angiograms were scored according to the Syntax score. The patients were divided into tertiles according to the Syntax score: lowest Syntax score tertile (Syntax score ≤ 22), intermediate Syntax score tertile (Syntax score of 23 to 32), and the highest Syntax score tertile (Syntax score ≥ 33). During the 1-year follow-up, the MACCE-free survival curves were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relation between the Syntax score and the incidence of MACCE. Performance of the Syntax score was studied with respect to predicting the rate of MACCE by receiver operator characteristic (ROC) curves with an area under the curve.

RESULTSThe overall Syntax score ranged from 6 to 66 with mean ± standard deviation of 27.9 ± 12.6 and a median of 26. At 1 year, the Syntax score significantly predicted the risk of MACCE (HR 1.07/U increase, 95%CI 1.04 to 1.11, P < 0.001). The rate of MACCE was significantly increased among patients in the highest Syntax score tertile (17.9%) as compared with those with the lowest Syntax score tertile (1.4%, P < 0.001) or intermediate Syntax score tertile (6.2%, P = 0.041). After the adjustment for all potential confounders, the Syntax score remained a significant predictor of the rate of MACCE (adjusted HR 1.12/U increase, 95%CI 1.05 to 1.20, P < 0.001). The Syntax score accurately predicted MACCE with an area under the receiver operator curve of 0.77 (95%CI 0.65 to 0.90, P < 0.001). A Syntax score of 29.5 was identified as the optimal cutoff to predict MACCE with a sensitivity of 82.4% and specificity of 65.6%.

CONCLUSIONThe Syntax score predicts the risk of MACCE in patients with 3-vessel disease undergoing PCI.

Adult ; Angioplasty, Balloon, Coronary ; methods ; Coronary Artery Disease ; pathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome

BACKGROUNDAdenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.

METHODSA total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.

RESULTSCompared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred.

CONCLUSIONAn adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Adenosine Diphosphate ; pharmacology ; Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; administration & dosage ; Prospective Studies ; Ticlopidine ; administration & dosage ; adverse effects ; analogs & derivatives

BACKGROUNDC-reactive protein (CRP) is a lowly expressed marker for inflammatory response. This study aimed to evaluate the prognostic value of baseline CRP levels in patients undergoing coronary revascularization in the context of modern medical treatment.

METHODSThis was a retrospective study in a single center. Four hundred and fourteen patients were enrolled, who underwent coronary revascularization and received adequate medication for secondary prevention of coronary heart disease. The study compared the follow-up clinical outcomes between high level CRP group (CRP > 5 mg/L) and low level one. The median follow-up time was 551 days.

RESULTSCompared with low CRP group, the relative risk (RR) of the major adverse cardiovascular and cerebral events (MACCE) in high CRP group was 5.131 (95%CI: 1.864-14.123, P = 0.002). There were no significant differences in death, myocardial infarction and stroke during the follow-up between two groups, but a higher risk of re-revascularization was found in high CRP group (RR 6.008, 95%CI: 1.667-21.665, P = 0.006). Cox regression analysis showed that only CRP level could contribute to MACCE during the follow-up. MACCE-free rate was much lower in high CRP group (Kaplan-Meier log-rank P < 0.001).

CONCLUSIONIn the context of modern medical treatment, the baseline level of CRP is an independent predictor for long-term prognosis in patients with coronary revascularization.

Aged ; C-Reactive Protein ; metabolism ; Coronary Disease ; metabolism ; surgery ; Female ; Humans ; Male ; Middle Aged ; Myocardial Revascularization ; methods ; Retrospective Studies

BACKGROUNDAlthough thrombolytic therapy with rescue percutaneous coronary intervention (PCI) is a common treatment strategy for ST-segment elevation acute myocardial infarction (STEMI), scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study.

METHODSThis multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients (age < or = 70 years) with STEMI who presented within 12 hours of symptom onset (mean interval > 3 hours). Patients were randomized to three groups: primary PCI group (n = 101); recombinant staphylokinase (r-Sak) group (n = 104); and recombinant tissue-type plasminogen activator (rt-PA) group (n = 106). For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery (IRA) patency; rescue PCI was performed in cases with TIMI flow grade < or = 2. Bare-metal stent implantation was planned for all patients.

RESULTSAfter randomization it required an average of 113.4 minutes to start thrombolytic therapy (door-to-needle time) and 141.2 minutes to perform first balloon inflation in the IRA (door to balloon time). Rates of IRA patency (TIMI flow grade 2 or 3) and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure (70.5% vs. 98.0%, P < 0.0001, and 53.0% vs. 85.9%, P < 0.0001, respectively). Rescue PCI with stenting was performed in 117 patients (55.7%) in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group (88.9% vs. 97.9%, P = 0.0222, and 68.4% vs. 85.0%, P = 0.0190, respectively). At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group (7.1% vs. 0, P = 0.0034). Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group (10.0% vs. 1.0%, P = 0.0380, and 28.10% vs. 8.91%, P = 0.0001, respectively).

CONCLUSIONSThrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Thrombolytic Therapy