Prolonged Dual Antiplatelet Therapy in Acute Myocardial Infarction Patients Without Revascularization: China Acute Myocardial Infarction Registry Study.

At least 12 months of dual antiplatelet therapy (DAPT) is 1 of the standards of care following percutaneous coronary intervention in patients with acute coronary syndrome. However, study on prolonged DAPT for patients with acute myocardial infarction (AMI) without revascularization is limited. We studied 1,744 patients with AMI without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014. These patients were on DAPT and did not experience AMI, stroke, or bleeding events at the 12-month follow-up. We divided them into 2 groups: 12-month DAPT group (DAPT for at least 12 months but <18 months) and 18-month DAPT group (DAPT for at least 18 months). The primary outcome was 24-month all-cause death. Overall, 1,221 patients (70.0%) took DAPT for ≥12 months but <18 months, whereas 523 patients (30.0%) took DAPT for ≥18 months. The proportion of patients at high ischemic risk and the proportion of patients at high bleeding risk were similar in the 2 groups. At 24 months, the all-cause mortality rate of the 18-month DAPT group was significantly lower than that for the 12-month DAPT group (3.7% vs 5.9%, p = 0.0471). The adjusted hazard ratio for all-cause death also showed statistical significance (0.59, 95% confidence interval 0.35 to 0.99, p = 0.0444). In conclusion, DAPT for at least 18 months appears to be associated with lower 24-month mortality for non-revascularization AMI patients without events within 12 months after onset.

Assessing vaccine hesitancy using the WHO scale for caregivers of children under 3 years old in China.

Introduction: Vaccine hesitancy may increase infectious disease burden and impede disease control efforts, while few studies have measured such a phenomenon with a standardized tool in China. This study aimed to test the validation of the Vaccine Hesitancy Scale (VHS) developed by the WHO SAGE Working Group among caregivers and examine demographic characteristics associated with caregiver hesitancy in six provinces of China. Methods: Using a multistage sampling design, this study was conducted in 36 immunization clinics in six provinces from December 2019 to August 2020. Caregivers of children aged 0-3 years were included. The VHS was used to assess vaccine hesitancy. The construct validity and internal consistency of the scale were assessed. Associations between caregivers' characteristics and vaccine hesitancy were examined by simple and multiple linear regression models. Results: Of the 3,359 participants included, a two-factor structure within the scale was identified, consisting of "lack of confidence" (1.89 ± 0.53) and "risks" (3.20 ± 0.75). Caregivers engaged in medical work expressed more confidence and were less concerned about risks compared to those of non-medical staff (p < 0.05). Participants with higher income levels were more confident (p < 0.05), while those surveyed after the COVID-19 pandemic, who were mothers, who had an older child, or who were raising a second or above birth child, had less concern about risks (p < 0.05). Discussion: We found that the VHS had acceptable reliability and construct validity and caregivers' hesitancy was driven more by concerns about risks than by the lack of confidence. Countering these concerns will be particularly important among non-medical staff, lower income, child's fathers, having a younger child, or raising first-birth child groups.

Cardiomyocyte-derived small extracellular vesicles can signal eNOS activation in cardiac microvascular endothelial cells to protect against Ischemia/Reperfusion injury.

Rationale: The crosstalk between cardiac microvascular endothelial cells (CMECs) and cardiomyocytes (CMs) has emerged as a key component in the development of, and protection against, cardiac diseases. For example, activation of endothelial nitric oxide synthase (eNOS) in CMECs, by therapeutic strategies such as ischemic preconditioning, plays a critical role in the protection against myocardial ischemia/reperfusion (I/R) injury. However, much less is known about the signals produced by CMs that are able to regulate CMEC biology. Here we uncovered one such mechanism using Tongxinluo (TXL), a traditional Chinese medicine, that alleviates myocardial ischemia/reperfusion (I/R) injury by activating CMEC eNOS. The aim of our study is to identify the signals produced by CMs that can regulate CMEC biology during I/R. Methods:Ex vivo, in vivo, and in vitro settings of ischemia-reperfusion were used in our study, with the protective signaling pathways activated in CMECs identified using genetic inhibition (p70s6k1 siRNA, miR-145-5p mimics, etc.), chemical inhibitors (the eNOS inhibitor, L-NNA, and the small extracellular vesicles (sEVs) inhibitor, GW4869) and Western blot analyses. TritonX-100 at a dose of 0.125% was utilized to inactivate the eNOS activity in endothelium to investigate the role of CMEC-derived eNOS in TXL-induced cardioprotection. Results: We found that while CMEC-derived eNOS activity was required for the cardioprotection of TXL, activation of eNOS in CMECs by TXL did not occur directly. Instead, eNOS activation in CMECs required a crosstalk between CMs and CMECs through the uptake of CM-derived sEVs. We further demonstrate that TXL induced CM-sEVs contain increased levels of Long Intergenic Non-Protein Coding RNA, Regulator Of Reprogramming (Linc-ROR). Upon uptake into CMECs, linc-ROR downregulates its target miR-145-5p leading to activation of the eNOS pathway by facilitating the expression of p70s6k1 in these cells. The activation of CMEC-derived eNOS works to increase survival in both the CMECs and the CMs themselves. Conclusions: These data uncover a mechanism by which the crosstalk between CMs and CMECs leads to the increased survival of the heart after I/R injury and point to a new therapeutic target for the blunting of myocardial I/R injury.

Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.