ABSTRACT
This study investigated the patterns of hematological adverse events related to daptomycin (DAP), tigecycline (TIG), vancomycin (VAN) and linezolid (LIN) in the FDA Adverse Event Reporting System (FAERS). Adverse event associations were analyzed through calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), multiple gamma Poisson shrinkage (MGPS), and Bayesian confidence propagation neural network (BCPNN). A comprehensive descriptive analysis was also conducted considering factors such as age, gender, daily dose, cumulative dose, and time to onset. The leading hematologic adverse events were eosinophilia for daptomycin, coagulation abnormalities and thrombocytopenia for tigecycline, thrombocytopenia, neutropenia, and anemia for linezolid, and thrombocytopenia, eosinophilia, and neutropenia for vancomycin. Most of the affected patients were over 55 years old. Daily doses for the tigecycline and daptomycin groups exceeded the standard daily dose. The times to onset were 14.00 days for daptomycin (interquartile range [IQR], 4.00-21.00), 6.00 days for tigecycline (IQR, 2.00-9.00), 10.00 days for linezolid (IQR, 4.00-16.5), and 10.00 days for vancomycin (IQR,5.00-20.00). It is essential to intensify early monitoring and identification of these adverse events, especially in the context of off-label dosages and for elderly patients and individuals taking medication for over one week.
ABSTRACT
Wound healing occupies a remarkable place in everyday pathology and remains a challenging clinical problem. In our previous study, we prepared a silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) (PVA/COS-AgNPs) nanofiber via electrospinning and revealed that it could promote wound healing; however, the healing mechanism remained unknown. Therefore, we aimed to clarify the mechanism underlying the accelerated healing effect of the PVA/COS-AgNPs nanofiber. The TGFß1/Smad signaling pathway is actively involved in wound healing. Considering the key role of this signaling pathway in wound healing, our preliminary study showed that the TGFß1 level was significantly increased during the early stage of wound healing. Thus, in this study, hematoxylin-eosin, Masson's trichrome, immunofluorescent staining, hydroxyproline content, quantitative real-time polymerase chain reaction, and Western blot analyses were used to analyze the wound healing in a rat model treated with gauze, the PVA/COS-AgNPs nanofiber, and the nanofiber plus SB431542 (an inhibitor of TGFß1 receptor kinase). The results showed that the PVA/COS-AgNPs nanofiber promoted wound healing and upregulated the expression levels of cytokines associated with the TGFß1/Smad signaling pathway such as TGFß1, TGFßRI, TGFßRII, collagen I, collagen III, pSmad2, and pSmad3. Inhibiting this pathway with SB431542 resulted in prevention of the PVA/COS-AgNPs nanofiber-associated salutary effects on the early stage of wound healing and relative cytokines expression. In conclusion, the wound healing effect of the PVA/COS-AgNPs nanofiber involves activation of the TGFß1/Smad signaling pathway.
