FGFR–TACC, found in different tumor types, is characterized by the fusion of a member of fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to a member of the transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks of FGFR–TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3–TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended. 相似文献
The intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) therapy is safe and efficient during the treatment of acute ischemic stroke. Nonetheless, the different outcomes among various stroke subgroups have limited data with regard to the safety and efficacy of cryptogenic stroke (CS). The present study compared the safety and efficacy when IVT with rt-PA was used for the treatment of CS and the other stroke subtypes.
Methods
This study classified the IVT with rt-PA patients within 4.5 hours after stroke onset, based on the trial of ORG 10172 in acute stroke treatment criteria in terms of diagnostic evaluation. The data were obtained from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China database, a large multicenter prospective registry. A multivariable logistic regression model was employed to compare the differences between the subtypes in symptomatic intracerebral hemorrhage (sICH) within 7 days and studied the mortality and the outcome during 90 days.
Results
In total, 1118 patients were recruited; of these, 131 (11.7%) suffered from CS and 987 (88.3%) with the other etiology. In the CS group, patients were younger than those in the other etiology groups (P < .001). Moreover, it had a lower prevalence of previous stroke (P?=?.0117), receiving antiplatelet drug in 24 hours prior to thrombolysis (P?=?.0017), and functional independence (mRS > 1 before stroke, P?=?.003). The CS group had lower blood pressure (systolic blood pressure P?=?.0001; diastolic blood pressure; P?=?.0212) before thrombolysis, atrial fibrillation (P < .001), and diabetes mellitus (P?=?.0005). Transient ischemic attack, hypertension, hyperlipidemia, blood glucose, receiving anticoagulants in 24 hours prior to thrombolysis, and standard dosage of rt-PA were equally distributed in both groups. After the adjustment of confounders between the CS and the other subgroups, no obvious differences were observed in sICH rate and mortality (P > .05) The CS patients exhibited excellent recovery (mRS, 0-1; 63.78%) and functional independence (mRS, 0-2; 74.8%) than the large artery atherosclerosis patients.
Conclusions
IVT with rt-PA is a safe and effective method for the treatment of CS patients. 相似文献
Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.
Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.
Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS. 相似文献
Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.
Methods
In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.
Results
AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.
Conclusions
These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium. 相似文献