RESUMEN
A risk-adapted treatment strategy is of crucial importance in patients with myelodysplastic syndromes (MDS). Previous risk prognostic scoring systems did not integrate molecular abnormalities. The new IPSS-Molecular (IPSS-M) model, combing genomic profiling with hematologic and cytogenetic parameters, was recently developed to evaluate the associations with leukemia-free survival (LFS), leukemic transformation, and overall survival (OS). However, it has not yet been widely validated in clinics. This study aims to further validate the prognostic power of IPSS-M based on real-world data and to compare the prognostic value of different scoring systems in patients with MDS. IPSS-M Web calculator was used to calculate a tailored IPSS-M score of the enrolled patient (N = 255), and the risk category was defined correspondingly. We next compared the IPSS-M prognostic power to that of IPSS, IPSS-R, and WPSS. We found that IPSS-M risk classification was statistically significant for 3-year OS and LFS. Compared with other tools, IPSS-M was superior in sensitivity and accuracy for 3-year OS and LFS. The mapping C-index between IPSS-R and IPSS-M categories resulted in improved discrimination across the OS, but not LFS and leukemic transformation. The result of different treatment options indicated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) can result in a better OS than those without allo-HSCT. In conclusion, IPSS-M was a valuable tool for risk stratification compared with other risk prognostic scoring systems. However, more studies should be conducted to explore the appropriate treatment options for different groups stratified by IPSS-M.
RESUMEN
Pulmonary hypertension (PAH) is a proliferative disease of pulmonary blood vessels, but the pathogenesis of pulmonary hypertension is still unclear. This article explores the role of tumor necrosis factor-α (TNF-α), tissue factor (TF), and coagulation function (CF) in the pathogenesis of PAH. PAH is often accompanied by vascular intima injury and muscular arterial media thickening. Coupled with the wide application of nanotargeted drugs in recent years, a targeted nanocarrier encapsulating sildenafil was prepared in this study. The particle size, PDI, zeta potential, drug loading, and encapsulation efficiency were 194.32 ± 17.31 nm, 0.28 ± 0.02, -6.34 ± 0.33, 24.61%, and 70.52%. The monocrotaline PAH rat model was constructed, and it was found that the levels of TNF-α, TF, and CF in the peripheral blood of PAH rats were abnormally increased. 30 PAH rats were randomly divided into 5 groups and injected with saline (NS group), sildenafil (sildenafil group), target the nanoempty carrier (TNC-E group), ordinary nanocarrier encapsulated sildenafil (CNC-sildenafil group), and targeted nanocarrier encapsulate sildenafil (TNC-sildenafil group). Compared with the NS group, the mean pulmonary artery pressure in the TNC-sildenafil group was lower (P < 0.05). Compared with the normal rat group, the pulmonary small blood vessel media thickness, TNF-α level, TF level, and the area of myocardial cells were increased in the NS group, sildenafil group, TNC-E group, and CNC-sildenafil group (P < 0.05). Compared with the NS group, the pulmonary small blood vessel media thickness, myocardial cell area, and the levels of TNF-α and TF in the TNC-sildenafil group were reduced (P < 0.05). Targeting nanocarrier encapsulation of sildenafil can obviously reduce the average pulmonary artery pressure in rats with pulmonary hypertension, improve pulmonary vascular media proliferation and myocardial hypertrophy, and restore the levels of TNF-α, TF, and CF to a normal state.
