An effective strategy for assembling the sex-limited chromosome.

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.

The role of NMDA receptors in rat propofol self-administration.

BACKGROUND: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. METHODS: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session. RESULTS: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01). CONCLUSION: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

Correlates and outcomes related to periprocedural myocardial injury during percutaneous coronary intervention for chronic total occlusion: Results from a prospective, single center PCI registry.

BACKGROUND: There is increasing interest in percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). Periprocedural myocardial injury (PMI) post CTO PCI is not uncommon, but true incidence and implications of PMI are not well understood. OBJECTIVES: This study aimed to investigate risk factors for PMI post CTO PCI and its implications for the 1-year clinical outcome of a Chinese population. METHODS: Baseline characteristics, procedure features, and major adverse cardiac events (MACE) at 1 year were assessed in 629 consecutive patients who underwent CTO PCI. PMI was diagnosed as an elevation of creatine kinase MB ≥3 times ULN 12-24 hr post procedure. Multivariate analysis was performed to determine the correlates of PMI and MACE at 1-year follow-up. RESULTS: In total, PMI was detected in 115 patients (18.3%). Compared with patients without PMI, those with PMI had a higher percentage of previous coronary artery bypass grafting (CABG), right coronary occlusion and side branch occlusion, and technical success was lower in the PMI group (90.4% vs. 96.7%, P = 0.003). One-year MACE-free survival was reduced in the PMI group (87.8% vs. 95.9%, P = 0.001). The final TIMI flow 0-1 (OR 2.23, 95%CI 1.06-4.87, P = 0.02), side branch occlusion (OR 2.67, 95%CI 1.19-7.11, P = 0.009), retrograde PCI (OR 1.35, 95%CI 1.10-2.74, P = 0.04), and history of prior CABG (OR 2.41, 95%CI 1.38-5.91, P = 0.01) were independent risk factors for the occurrence of PMI. CONCLUSIONS: In this unique Chinese cohort, PMI post CTO PCI was associated with several clinical and angiographic factors and exerts an adverse effect on 1-year clinical outcomes.

Periprocedural use of tirofiban in elective percutaneous coronary intervention for long coronary lesions in stable patients with overlapping drug-eluting stents--the PETITION study: a prospective, randomized, multicenter study.

BACKGROUND AND PURPOSE: Patients are at risk of developing periprocedural myonecrosis after percutaneous coronary intervention (PCI). We investigated whether the use of the platelet glycoprotein (GP) IIb/IIIa receptor inhibitor tirofiban could reduce periprocedural myocardial infarction (PMI) in patients with stable coronary artery disease undergoing elective PCI with overlapping stent implantation for long lesions. METHODS: A total of 748 stable angina patients with long lesions (≥ 40 mm in length) treated with overlapping stent implantation were randomly assigned to receive tirofiban (tirofiban group; n = 373) or conventional therapy (control group; n = 375). Intravenous tirofiban was initiated before PCI and maintained for 12 hr after the procedure. The primary endpoint was PMI, defined as an elevation in CK-MB > 3 times the upper limit of normal 12 hr after the index procedure. The secondary endpoint was major adverse cardiac events (MACE), including cardiac death, target vessel revascularization, and recurrent MI (re-MI), at one-year of clinical follow-up. The safety end-points included Thrombolysis in Myocardial Infarction (TIMI) major bleeding and stent thrombosis. RESULTS: Despite comparable angiographic and procedural characteristics, in the intention-to-treatment analysis, the primary endpoint was significantly reduced in the tirofiban group (4.0% vs. 11.5%, P < 0.001). Multivariate analysis revealed that the adjunctive use of tirofiban was the only negative predictor of PMI (OR 0.41, 95% CI 0.28-0.81, P < 0.01). At one-year of clinical follow-up, the overall occurrence of MACE was significantly lower in the tirofiban group (13.4% vs. 22.7%, P = 0.001). The rate of TIMI major bleeding and stent thrombosis did not differ significantly between the two groups. CONCLUSION: Our results show that the adjunctive use of tirofiban reduces the occurrence of PMI and MACE at one year in stable coronary artery disease patients undergoing elective PCI for long lesions with overlapping stent implantation.

Comparison of biodegradable polymer versus durable polymer sirolimus-eluting stenting in patients with acute st-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of the RESOLVE study.

BACKGROUND: Sirolimus-eluting stents (SES) with a biodegradable polymer coating have demonstrated promising results but have not been compared to SES with a durable polymer in high-risk patients. We compared the efficacy of these 2 stent types in patients with acute myocardial infarction (STEMI). METHODS: One thousand one hundred ninety-two STEMI patients were randomized to receive SES coated with biodegradable (n = 596) or durable polymer (n = 596). The study end-point was the composite of major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction (MI), or target lesion revascularization (TLR) at 1-year follow-up. Secondary end-points included individual components of primary end-point and stent thrombosis. RESULTS: Compared with durable polymer SES, the noninferiority of SES with biodegradable polymer coating was established by an absolute risk difference of 0.9% in the primary end-point (12.4% vs. 13.3%, P = 0.67) and an upper limit of one-sided 95% confidence interval (CI) of 2.96% (P for noninferiority = 0.001). Rate of death, recurrent MI, and TLR were 7.9% and 8.6% (HR: 0.92; 95% CI: 0.61-1.38, P = 0.67), 2.9% and 3.5% (HR: 0.80; 95% CI: 0.42-1.54, P = 0.51), and 2.0% and 3.2% (HR: 0.62; 95% CI: 0.30-1.30, P = 0.20) in the biodegradable polymer SES and durable polymer SES group at 1-year clinical follow-up, respectively. Despite similar rates of 30-day ARC definite/probable stent thrombosis, late stent thrombosis (stent thrombosis occurring beyond 30 days) was lower with biodegradable polymer SES (0.7% vs. 2.2%, P = 0.028). CONCLUSIONS: In patients undergoing primary PCI for STEMI, the use of biodegradable polymer SES was associated with noninferior 1-year rates of MACE compared with durable polymer SES.

Randomized comparison of intracoronary tirofiban versus urokinase as an adjunct to primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: results of the ICTUS-AMI trial.

BACKGROUND: No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI. METHODS: A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%. RESULTS: In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P < 0.05). CONCLUSIONS: An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.

Improved outcomes from transradial over transfemoral access in primary percutaneous coronary intervention for patients with acute ST-segment elevation myocardial infarction and upstream use of tirofiban.

BACKGROUND: Transradial access has been increasingly used during primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI) in last decade. Clinical benefits of upstream use of tirfiban therapy in STEMI patients treated by primary PCI have been reported. We investigated the merits of transradial vs. transfemoral access in primary PCI for STEMI patients with upstream use of tirofiban. METHODS: Patients with STEMI treated with tirofiban between December 2006 and October 2012 then by primary PCI were compared between transradial (n = 298) and transfemoral (n = 314) access. Baseline demographics, angiographic and PCI features and primary endpoint of major adverse cardiac events (MACE) at 30-day clinical follow-up were recorded. RESULTS: Baseline and procedural characteristics were comparable between the two groups, apart from more patients in transradial group had hypertension and were treated by thrombus aspiration during primary PCI. Significantly fewer MACE occurred in the transradial group (5.4%) compared with the transfemoral group (9.9%) at 30-day clinical follow-up. Major bleeding events at 30-day clinical follow-up were 0 in transradial group and in 2.9% of transfemoral group. Multivariate analysis confirmed transradial approach as an independent negative predictor of 30-day MACE (HR 0.68; 95%CI 0.35 - 0.91; P = 0.03). CONCLUSIONS: Using transradial approach in primary PCI for acute STEMI infarction patients treated with tirofiban was clearly beneficial in reducing bleeding complications and improving 30-day clinical outcomes.

Impact of elevated serum glycated albumin levels on contrast-induced acute kidney injury in diabetic patients with moderate to severe renal insufficiency undergoing coronary angiography.

BACKGROUND: Glycated albumin (GA) has been shown to be a better indicator than glycosylated hemoglobin A1c (HbA1c) in terms of severity of renal impairment in patients with type 2 diabetes mellitus (T2DM). This study aimed to determine whether elevated serum GA levels are associated with an increased risk for contrast-induced acute kidney injury (CI-AKI) and worse clinical outcome in patients with T2DM and at least moderate renal insufficiency (RI) undergoing coronary angiography. METHODS: Serum levels of fasting blood glucose (FBG), HbA1c and GA were measured in 1030 patients with T2DM and moderate to severe RI (eGFR 15-59 mL/min/1.73 m(2)). CI-AKI was defined as ≥ 25% increase in serum creatinine within 72 h after the procedure. Receiver-operating characteristic curve was constructed to assess the predictive value of GA, HbA1c and FBG for CI-AKI. Multivariable logistic regression model was developed to identify risk factors for CI-AKI, and Kaplan-Meier curve analysis was used to compare the rates of dialysis and major adverse cardiac events (MACE) during one-year follow-up. RESULTS: The overall rate of CI-AKI was 11.1%. GA was significantly higher in patients with CI-AKI than in those without, and correlated positively with changes of renal function after the procedure. After adjusting for age, sex, left ventricular ejection fraction, multi-vessel disease, type and volume of contrast media, FBG, and HbA1c, GA remained an independent risk factor for CI-AKI. GA ≥ 21% was associated with increased rates of dialysis and MACE during one-year follow-up in patients with or without CI-AKI. CONCLUSIONS: Increased GA level serves as a valuable risk factor for CI-AKI and indicates poor one-year clinical outcome in patients with T2DM and moderate to severe RI.

Beneficial effects of intracoronary tirofiban bolus administration following upstream intravenous treatment in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the ICT-AMI study.

BACKGROUND: We investigated whether an additional intracoronary tirofiban bolus administration following upstream intravenous treatment could further improve myocardial reperfusion and clinical outcome in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 453 eligible STEMI patients were randomly allocated to intracoronary bolus administration of tirofiban (10 µg/kg; n=229) or saline (10 mL; n=224) during primary PCI, followed by intravenous tirofiban infusion (0.15 µg/kg/min) for 24-36 h. Serum levels of P-selectin, vWF, CD40L and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary bolus administration. The primary endpoint was ST-segment resolution (STR) at 90 min after the procedure. Second endpoints included corrected TIMI frame count (cTFC), left ventricular volumes and ejection fraction (EF), and major adverse cardiac events (MACE) at 30-day and 6-month follow-up. RESULTS: Intracoronary tirofiban administration resulted in a higher rate of completed STR (59.0% vs. 44.6%, P=0.002), lower cTFC (21.6±5.4 vs. 23.7±7.8, P=0.048), and significantly reduced coronary sinus levels of P-selectin, vWF, CD40L and SAA. Patients treated with intracoronary tirofiban had a trend toward less MACE at 30 days (3.1% vs. 6.7%, P=0.072). At 6 months, left ventricular end-systolic volume was smaller, EF was higher and MACE-free survival was improved (96.1% vs. 90.6%, P=0.020) in the intracoronary tirofiban group. CONCLUSIONS: An additional intracoronary tirofiban bolus administration following upstream intravenous treatment reduces coronary circulatory platelet activation and inflammatory process, and significantly improves myocardial reperfusion and left ventricular function as well as 6-month MACE-free survival for STEMI patients undergoing primary PCI.

Hemocompatibility of drug-eluting coronary stents coated with sulfonated poly (styrene-block-isobutylene-block-styrene).

The presence of polymer coating on a coronary stent is a major mediator of coronary inflammation reaction thereby affects re-endothelialization. Poly(styrene-block-isobutylene-block-styrene) (SIBS) is one of the most attractive alternatives to serve as stent coating, but has shown less than optimal biocompatibility. Increasing the sulfonic acid content in the polymer can result in increased strength and hydrophilicity. The present study was undertaken to determine the mechanism of action and in vivo efficacy of sulfonated SIBS (S-SIBS) designed specifically as a stent polymer with reduced inflammatory potential and greater endothelialization preservation potential. The blood compatibility of S-SIBS in vitro and its ability to support the attachment of human umbilical vein endothelial cells (HUVECs) were first assessed to get some insight into its potential use in vivo. Baer metal stent (BMS), S-SIBS-coated stent without drug (BMS Plus S-SIBS), standard drug-eluting stent (DES) and S-SIBS-coated drug-eluting stent (DES Plus S-SIBS) were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 28 and 180 days, and re-endothelialization was evaluated at 7 and 28 days post stents implantation. The results showed that DES Plus S-SIBS exhibited similar ability to reduce neointimal hyperplasia but preserved endothelialization compared with standard DES. These results suggest potentially promising performance of S-SIBS-coated stent in human clinical applications of coronary stenting.

Impact of angina prior to acute ST-elevation myocardial infarction on short-term outcomes after primary percutaneous coronary intervention: results from the Shanghai Registry of Acute Coronary Syndrome (SRACE).

BACKGROUND: The clinical significance of ischemic chest pain before acute ST-elevation myocardial infarction (STEMI) remains an interesting issue of investigation particularly in the era of percutaneous coronary intervention (PCI). This study aimed to assess the impact of angina prior to STEMI on short-term clinical outcomes in patients with acute STEMI undergoing primary PCI. METHODS: Among a total of 875 consecutive patients with STEMI undergoing primary PCI, 292 had episodes of angina within 24 hours of STEMI (PA group) and the remaining 583 were free of anginal symptoms (non-PA group). Clinical characteristics, angiographic and procedural features, and in-hospital and 30-day outcomes were compared between the two groups. RESULTS: Diabetes was less common (17.5% vs. 23.3%, P = 0.04) and symptom-to-door time was shortened ((191.6 ± 96.8) minutes vs. (357.2 ± 341.9) minutes, P < 0.001) in the PA group than in the non-PA group. Patients with angina prior to STEMI had fewer totally or nearly totally occluded infarct-related artery (TIMI flow grade 0 - 1) at initial angiography (75.0% vs. 90.7%, P < 0.001), and achieved more TIMI flow grade 3 after primary PCI (84.2% vs. 78.2%, P = 0.04). These were associated with higher rates of overall procedural success (95.9% vs. 91.8%, P = 0.02) and of complete ST-segment resolution at 90 minutes after the procedure (51.7% vs. 40.3%, P = 0.001). During a 30-day clinical follow-up, the left ventricular ejection fraction was significantly improved ((53.0 ± 8.6)% vs. (51.1 ± 9.7)%, P = 0.002) and the primary endpoint of major adverse cardiac events was reduced in the PA group (7.2% vs. 12.7%, P = 0.01). CONCLUSION: Presence of angina prior to acute STEMI is associated with better outcome at a 30-day clinical follow-up in patients undergoing primary PCI.

Prevalence, clinical characteristics and outcome in patients with chronic heart failure and diabetes.

BACKGROUND: Chronic heart failure (CHF) and diabetes mellitus portend high morbidity and mortality because of an interrelated pathophysiologic process. This large cohort study aimed to analyze the prevalence, clinical characteristics and long-term outcome of patients with CHF and diabetes. METHODS: A total of 1119 patients with NYHA functional class II - IV and left ventricular ejection fraction (LVEF) < 45% between January 1995 and May 2009 were recruited. Clinical variables, biochemical and echocardiographic measurements were retrospectively reviewed, and composite major cardiac events (MCE) including death, heart transplantation, and refractory heart failure requiring multiple hospitalizations were recorded. RESULTS: The prevalence of CHF with diabetes was progressively increased with time (16.9% in 1995 - 1999; 20.4% in 2000 - 2004, and 29.1% in 2005 - 2009) and age (18.5% in < 60 years, 26.6% in 60 - 80 years, and 26.6% in > 80 years). Compared with CHF patients without diabetes, those with diabetes had worse cardiac function, more abnormal biochemical changes, and higher mortality. Treatment with glucose-lowering agents significantly improved LVEF and decreased MCE. An elevated serum HbA1c level was associated with large left ventricular end-systolic diameter (P < 0.05), decreased LVEF (P < 0.01) and reduced survival (P < 0.05). Multivariable Logistic regression analysis revealed that after adjustment for confounding factors, NYHA functional class (OR 2.65, 95%CI 1.14 - 6.16, P = 0.024) and HbA1c level >or= 7% (OR 2.78, 95%CI 1.00 - 7.68, P = 0.049) were independent risk factors for adverse outcomes in CHF patients with diabetes. CONCLUSIONS: Prevalence of CHF with diabetes was increasing during past decades, and patients with CHF and diabetes had worse clinical profiles and prognosis. Aggressive anti-CHF and diabetes therapies are needed to improve overall outcomes for these patients.