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BackgroundThis study aimed to comprehensively explore the occurrence and risk factors for adverse events (AEs) and adverse drug reactions (ADRs) (especially for thrombocytopenia and bleeding) in Chinese patients with high bleeding risk (older adults, or complicated with diabetes mellitus or renal function impairment) undergoing percutaneous coronary intervention (PCI) with bivalirudin as an anticoagulant.MethodsA total of 1,226 patients with high bleeding risk who received PCI with bivalirudin as an anticoagulant from 27 Chinese medical centers were enrolled in this prospective, multi-center, intensive monitoring study. AEs, ADRs, thrombocytopenia, and bleeding were collected from admission to 72 h post-bivalirudin administration; subsequently, patients were followed up on the 30th day with the safety data collected as well.ResultsAdverse events were observed in 198 (16.2) patients, among which severe AEs occurred in 16 (1.3%) patients. Meanwhile, bivalirudin-related ADRs were reported in 66 (5.4%) patients, among which 5 (0.4%) patients experienced bivalirudin-related severe ADRs. Besides, thrombocytopenia and bleeding occurred in 45 (3.7%) and 19 (1.5%) patients, respectively. The subsequent multivariate logistic analysis revealed that age >75 years [p = 0.017, odds ratio (OR) = 1.856] and spontaneous coronary artery dissection (SCAD) (p = 0.030, OR = 2.022) were independently related to higher ADR risk; SCAD (p = 0.017, OR = 2.426) was independently correlated with higher thrombocytopenia risk, while radial artery access (p = 0.015, OR = 0.352) was independently correlated with lower thrombocytopenia risk; and the administration of bivalirudin preoperatively or intraoperatively (p = 0.013, OR = 5.097) was independently associated with higher bleeding risk.ConclusionBivalirudin presents a favorable safety profile regarding ADRs, thrombocytopenia, and bleeding in Chinese patients with high bleeding risk undergoing PCI.

BackgroundAcute myocardial infarction (AMI) is one of the most common causes of mortality around the world. Early diagnosis of AMI contributes to improving prognosis. In our study, we aimed to construct a novel predictive model for the diagnosis of AMI using an artificial neural network (ANN), and we verified its diagnostic value via constructing the receiver operating characteristic (ROC).MethodsWe downloaded three publicly available datasets (training sets GSE48060, GSE60993, and GSE66360) from Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified between 87 AMI and 78 control samples. We applied the random forest (RF) and ANN algorithms to further identify novel gene signatures and construct a model to predict the possibility of AMI. Besides, the diagnostic value of our model was further validated in the validation sets GSE61144 (7 AMI patients and 10 controls), GSE34198 (49 AMI patients and 48 controls), and GSE97320 (3 AMI patients and 3 controls).ResultsA total of 71 DEGs were identified, of which 68 were upregulated and 3 were downregulated. Firstly, 11 key genes in 71 DEGs were screened with RF classifier for the classification of AMI and control samples. Then, we calculated the weight of each key gene using ANN. Furthermore, the diagnostic model was constructed and named neuralAMI, with significant predictive power (area under the curve [AUC] = 0.980). Finally, our model was validated with the independent datasets GSE61144 (AUC = 0.900), GSE34198 (AUC = 0.882), and GSE97320 (AUC = 1.00).ConclusionMachine learning was used to develop a reliable predictive model for the diagnosis of AMI. The results of our study provide potential gene biomarkers for early disease screening.

Inflammation plays an important role in aortic dissection (AD). Macrophages are critically involved in the inflammation after aortic injury. Neuraminidases (NEUs) are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids, which is emerging as a regulator of macrophage-associated immune responses. However, the role of neuraminidase 1 (NEU1) in pathological vascular remodeling of AD remains largely unknown. This study sought to characterize the role and identify the potential mechanism of NEU1 in pathological aortic degeneration. After β-aminopropionitrile monofumarate (BAPN) administration, NEU1 elevated significantly in the lesion zone of the aorta. Global or macrophage-specific NEU1 knockout (NEU1 CKO) mice had no baseline aortic defects but manifested improved aorta function, and decreased mortality due to aortic rupture. Improved outcomes in NEU1 CKO mice subjected to BAPN treatment were associated with the ameliorated vascular inflammation, lowered apoptosis, decreased reactive oxygen species production, mitigated extracellular matrix degradation, and improved M2 macrophage polarization. Furthermore, macrophages sorted from the aorta of NEU1 CKO mice displayed a significant increase of M2 macrophage markers and a marked decrease of M1 macrophage markers compared with the controls. To summarize, the present study demonstrated that macrophage-derived NEU1 is critical for vascular homeostasis. NEU1 exacerbates BAPN-induced pathological vascular remodeling. NEU1 may therefore represent a potential therapeutic target for the treatment of AD.

Stimulating and improving the creativity of employees are both theoretically and practically important. The relationship between prosocial motivation and creativity has gradually gained attention in recent years; however, in the context of controlling for intrinsic motivation, the influence process and results between the two are not yet clear. Based on the motivated information processing model, componential theory of creativity, and regulatory focus theory, this study analyzed the mediating role of knowledge sharing and the moderating role of regulatory focus in the relationship between prosocial motivation and the creativity of employees. For this, we used the PROCESS program and the bootstrap method to test the theoretical hypotheses. Consequently, a survey of 320 Chinese employees revealed that, under the condition of controlling for intrinsic motivation, the prosocial motivation of employees was positively related to creativity and partially mediated by knowledge sharing. Furthermore, regulatory focus negatively moderated the correlation between prosocial motivation and knowledge sharing. Specifically, we found that the higher the prevention focus was, the weaker the effect prosocial motivation had on knowledge sharing. Contrary to the hypothesis, promotion focus also played a negative moderating role. Thus, the results revealed the mechanism and boundary conditions of prosocial motivation on creativity. This study expands the research on prosocial motivation and provides guidance on how managers can enhance the creativity of their employees.