Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine whether in patients presenting with ST-segment-elevation myocardial infarction a single bolus recombinant staphylokinase (r-SAK) before timely PCI leads to improved patency of the infarct-related artery and reduces the infarct size. METHODS: This is an open-label, prospective, multicenter, randomized study. We enrolled patients aged 18 to 75 years who were within 12 hours of symptom onset of ST-segment-elevation myocardial infarction and expected to undergo PCI within 120 minutes. Patients were administered loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive 5 mg bolus of r-SAK or normal saline intravenously before PCI. The primary end point was Thrombolysis in Myocardial Infarction flow grade 2 to 3 or grade 3 in the infarct-related artery 60 minutes after thrombolysis. The infarct size was detected by cardiac magnetic resonance 5 days after randomization. The safety end point was major bleeding (Bleeding Academic Research Consortium ≥3) during 30-day follow-up. RESULTS: A total of 283 patients were screened from 8 centers and 200 were randomized (median age, 58.5 years; 14% female). The median symptom to thrombolysis time was 252.5 (interquartile range, 142.8-423.8) minutes and thrombolysis to coronary arteriography was 50.0 (interquartile range, 37.0-66.0) minutes. Patients randomized to r-SAK compared with normal saline more often had Thrombolysis in Myocardial Infarction flow grade 2 to 3 (69.0% versus 29.0%; P<0.001) and Thrombolysis in Myocardial Infarction flow grade 3 (51.0% versus 18.0%; P<0.001) and had smaller infarct size (21.91±10.84% versus 26.85±12.37%; P=0.016). There was no increase in major bleeding (r-SAK, 1.0% versus control, 3.0%; P=0.616). CONCLUSIONS: A single bolus r-SAK before primary PCI for ST-segment-elevation myocardial infarction improves infarct-related artery patency and reduces infarct size without increasing major bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05023681.

Comprehensively Analyze the Prognosis Significance and Immune Implication of PTPRO in Lung Adenocarcinoma.

Immunotherapy for lung adenocarcinoma (LUAD) is considered to be a promising treatment option, but only a minority of patients benefit from it. Therefore, it is essential to clarify the regulation mechanism of the tumor immune microenvironment (TIM) of the LUAD. Receptor-type protein tyrosine phosphatase (PTPRO) has been shown to be a tumor suppressor in a variety of tumor; however, its role in LUAD has never been reported. In this study, we first found that PTPRO was lowly expressed in LUAD and positively correlated with patient prognosis. Next, we investigated the relationship between PTPRO and clinical characteristics, and the results showed that gender, age, T, and stage were closely related to the expression level of PTPRO. Moreover, we performed univariate and multivariate analyses, and the results revealed that PTPRO was a protective factor for LUAD. By constructing a nomogram based on the expression level of PTPRO and various clinical characteristics, it was proved that the nomogram has a good predictive capacity. Furthermore, we analyzed the coexpression network of PTPRO through multiple databases and performed GO and KEGG enrichment analyses. The results demonstrated that PTPRO was involved in the regulation of multiple immune pathways. In addition, we analyzed whether PTPRO expression of LUAD regulate immune cell infiltration and the results demonstrated that PTPRO was closely related to the infiltration of various immune cells. Finally, we predicted LUAD sensitivity to chemotherapeutics and response to immunotherapy by PTPRO expression levels. The results showed that PTPRO expression level affect the sensitivity of various chemotherapeutic drugs and may be involved in the efficacy of immunotherapy. These results we obtained suggested that PTPRO is closely related to the prognosis and TIM of LUAD, which may be a potential immunotherapeutic target for LUAD.

Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention.

Background Insulin receptor substrate-1 (IRS-1) rs956115 is associated with vascular risk in patients with coronary artery disease and concomitant diabetes. CYP2C19*2 (rs4244285) modulates clopidogrel response and predicts the outcome of coronary artery disease. This study was designed to explore the association between IRS-1, CYP2C19*2 genotypes, platelet reactivity, and 1-year outcome in patients with coronary artery disease undergoing percutaneous coronary intervention. Methods and Results Genotyping was performed using an improved multiplex ligation detection reaction technique. Platelet aggregation was assessed by light transmission aggregometry. Major adverse cardiovascular events were defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke. A total of 2213 consecutive patients were screened and 1614 were recruited. At 1 month, patients with IRS-1 CG genotype had significantly lower levels of ADP-induced platelet aggregation compared with patients with CC homozygotes. Patients with IRS-1 CG or GG genotype had a 2.09-fold higher risk of major adverse cardiovascular events compared with those with CC homozygotes (95% CI, 1.04-4.19; P=0.0376). By comparison, patients with CYP2C19*2 GA or AA genotype had higher ADP-induced platelet aggregation compared with patients with GG homozygotes. Although there was no significant difference in risk of major adverse cardiovascular events between patients with GA/AA and GG genotypes, patients with GA genotype had a 2.19-fold higher risk than those with GG homozygotes (95% CI, 1.13-4.24; P=0.0200). No interaction between IRS-1 and CYP2C19*2 genotypes was observed. Conclusions In patients following percutaneous coronary intervention, IRS-1 GG/CG and CYP2C19*2 GA genotypes were associated with 2.09- and 2.19-fold increased cardiovascular risk, respectively, at 1-year follow-up. The association between IRS-1 genotypes and major adverse cardiovascular events appeared to be independent of known clinical predictors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01968499.

Use of handheld electrocardiograph (SnapECG) for the remote monitoring of arrhythmias.

Objective: To investigate the value of a SnapECG monitoring in diagnosing arrhythmias compared with the conventional management. Methods: In the first phase, the SnapECG and 12-lead electrocardiogram (ECG) were simultaneously adopted to detect arrhythmias in 439 hospitalized patients. The accuracies of the SnapECG in detecting different arrhythmias were assessed. In the second phase, 62 patients with palpitations were randomized to receive the SnapECG monitoring or conventional management for 3 months. The diagnosis rate, time of diagnosis, episodes before diagnosis, associated expenses, and scores of the modified European Heart Rhythm Association (EHRA), Self-rating Anxiety Scale (SAS), and the 36-item short-form health survey questionnaire (SF-36) were compared between groups. Results: In the first phase, the SnapECG monitoring showed a sensitivity of 83.55% and specificity of 96.79% in identifying tachyarrhythmias, and a sensitivity of 95.29% and specificity of 97.54% in identifying bradyarrhythmias. In the second phase, 1642 ECGs were recorded by the SnapECG, among which 290 abnormal ECGs were identified. Compared with the conventional management, the SnapECG monitoring increased the diagnosis rate of symptomatic arrhythmias (70.97% vs. 19.35%, P < 0.05), shortened the time of diagnosis (48.26 ± 36.78 days vs. 71.45 ± 30.01 days, P < 0.05) and consequently reduced the episodes of symptomatic arrhythmias prior to establishing diagnosis. The scores of modified EHRA, SAS, SF-36 significantly improved at 3-month compared with their baseline levels in the SnapECG group. Conclusions: Remote monitoring with the SnapECG can achieve early diagnosis of symptomatic arrhythmias. However, its sensitivity in identifying P-wave-related arrhythmias warrants further improvement.

ABCA1 variants rs2230806 (R219K), rs4149313 (M8831I), and rs9282541 (R230C) are associated with susceptibility to coronary heart disease.

BACKGROUND: To investigate the association between three single nucleotide polymorphisms (SNPs) of ABCA1 gene and susceptibility to coronary heart disease (CHD) in Chinese Han population. METHODS: A total of 484 CHD patients and 488 controls were included in the study. Three SNPs rs2230806 (R219K), rs4149313 (M8831I), and rs9282541 (R230C) in ABCA1 gene were genotyped by SNaPshot. RESULTS: Single nucleotide polymorphism rs1800977 was associated with susceptibility to CHD (AA vs GG, P = 0.013; A vs G, P = 0.029; recessive model, P = 0.020). Rs4149313 (AA vs GG, P = 0.010; recessive model, P = 0.011) and rs9282541 (T vs C, P = 0.029; dominant model, P = 0.039) were also risk factor for CHD. CONCLUSION: This study suggests that three SNPs rs2230806, rs4149313, and rs9282541 in ABCA1 gene are significantly associated with susceptibility to CHD; further mechanism should be performed to be applied to drug research and development.

Behavioural recovery correlated with MRI in a rat experimental stroke model.

PRIMARY OBJECTIVE: To characterize a necrotic lesion using MRI and motor recovery using behavioural methods. RESEARCH DESIGN: Stroke model based on two steps: (1) development of a lesion using MR-imaging parameters and (2) behavioural recovery. METHODS AND PROCEDURES: Seventy male Sprague-Dawley rats were used. A focal lesion of the right sensorimotor cortex was induced photochemically. MAIN OUTCOMES AND RESULTS: The maximum volume of oedema and the lesion damage was reached by approximately 6 hours. In the lesion area, the apparent diffusion coefficient (ADC) increased from 6 hours, then decreased from 24 hours. All animals spontaneously recovered motor function by day 10, despite the continued presence of the cortical lesion. CONCLUSIONS: The results show that this model mimics a core lesion, as well as the late phase in a human stroke episode. This model might be used for longitudinal study of the basic mechanisms of motor recovery.