The mechanism and treatment of targeted anti-tumour drugs induced cardiotoxicity.

As the intensive anti-tumour therapy and combination of multiple anti-tumour drugs, cardiotoxicity events caused by anti-tumour drugs have also increased significantly, and the incidence of cardiotoxicity also increased with survival time. Different types of anti-tumour drugs could cause all kinds of cardiotoxicity which increase the difficulties in treatment and even live threatening. In this review, we concentrated in the targeted anti-tumour drugs such as human epidermal growth factor receptor-2 (HER2) inhibitors, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and proteasome inhibitors (Pls). The molecular mechanism of how these drugs induce cardiotoxicity is introduced which includes several signal pathways. These drugs induced cardiotoxicity involved heart failure, hypertension, atherosis and thrombosis, QT interval prolongation, and myocarditis. Some of the cardiotoxicity could be moderate and reversible but others could have happened severely.The aim of this review is to summarise the targeted anti-tumour drugs induced cardiotoxicity and treatment strategies.

Ceftazidime-Avibactam for Carbapenem-Resistant Gram-Negative Bacteria Infections: A Real-World Experience in the ICU.

Purpose: Ceftazidime-avibactam (C-A) is a treatment option for carbapenem-resistant gram-negative bacterial (CR-GNB) infections, but little is known regarding its suitability for the intensive care unit (ICU). The current study aimed to analyze use of C-A for critically ill patients, determine independent predictors of clinical outcome and mortality and explore routine dosages for patients in continuous renal replacement therapy (CRRT). Patients and Methods: A single-center, retrospective and observational study was conducted in critically ill patients receiving different C-A-based therapies for CR-GNB infections in a tertiary teaching hospital in Beijing, China. Demographic data, severity of infection, clinical outcomes and mortality were assessed. The primary and secondary outcome of this study was 90-day all-cause mortality and 14-day clinical response, respectively. Results: A total of 43 patients with CR-GNB infection were enrolled, including 14 (32.6%) patients received C-A monotherapy. C-A monotherapy and combination with other agents did not affect 14-day clinical response or 90-day survival. All-cause mortality at 90-days was 39.5% (17/43). Multivariate Cox analysis showed that concomitant with bloodstream infection was independent risk factors for 90-day mortality and that the time to initiation of C-A and Acute Physiology and Chronic Health Evaluation (APACHE) score was independent predictors of 14-day clinical response. Five CRRT patients who received high-dose C-A therapy (>3.75 g/d) had prolonged survival compared with 5 who received low-dose C-A (<3.75 g/d, p = 0.03). Conclusion: C-A was an effective therapy for severe CR-GNB infections and clinical response correlated with the time of C-A initiation. A dosage >3.75g/d C-A was associated with prolonged survival of CRRT patients. Randomized controlled trials or multicenter studies are needed to confirm these findings.

MicroRNA-27b-3p inhibits apoptosis of chondrocyte in rheumatoid arthritis by targeting HIPK2.

BACKGROUND: Understanding the mechanism of chondrocytes degeneration could provide a new potential therapeutic idea for rheumatoid arthritis (RA) treatment. MicroRNA-27b-3p (miR-27b-3p) has been shown to regulate a variety of cell behaviors in various cell types. However, the role of miR-27b-3p in RA remains unknown. MATERIALS AND METHODS: Expression of miR-27b-3p and HIPK2 in cartilage tissues and chondrocytes was characterized using qRT-PCR and Western blot. MiR-27b-3p was overexpressed or suppressed in chondrocytes to observe the potential role of miR-27b-3p. RESULTS: We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells using qRT-PCR. Dual-luciferase reporter assay validated HIPK2 is a direct target of miR-27b-3p, confirmed by Western blot results. Pearson correlation presented that there was a significantly negative correlation between miR-27b-3p and HIPK2 mRNA. Overexpression of miR-27b-3p significantly reduced the expression of pro-apoptotic protein c-caspase3 and increased the expression of anti-apoptotic Bcl-2; however, downregulation of miR-27b-3p has a significant effect of inducing apoptosis. Furthermore, overexpression of miR-27b-3p combined with recombinant HIPK2 protein showed the inhibitory effect of miR-27b-3p was abolished by HIPK2. CONCLUSION: We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells. Further in vitro studies demonstrated that miR-27b might inhibit chondrocyte apoptosis and thus attenuate RA development by directly inhibiting HIPK2 expression.