Activation of the hedgehog pathway in chronic myelogeneous leukemia patients

<p>Abstract</p> <p>Background</p> <p>Hedgehog (Hh) signaling pathway is involved in regulation of many tissues development and oncogenesis. Recently, Hh signaling has been identified as a required functional pathway for leukemia stem cells(LSCs), and loss of this pathway impairs leukemia progression.</p> <p>Objectives</p> <p>The aim of this study was to determine the expression of Hedgehog signaling molecules in Chronic Myelogeneous Leukemia (CML) patients and normal people by semiquantitative polymerase chain reaction (PCR) and to correlate mRNA expression to patients' clinical data.</p> <p>Results</p> <p>Here, we showed that Sonic hedgehog (Shh), Smoothened (Smo), and Gli1 genes of Hh signaling were significantly upregulated in CML patients when compared with normal people (P < 0.001). The levels of Shh, Smo mRNA in chronic phase of CML patients were obviously lower than that in blast crisis (p < 0.05). There were no significant differences of Shh, Ptch1, Smo, Gli1 mRNA expression found when comparing CML patients of chronic phase(CP) with imatinib(IM) treated or not(p > 0.05).</p> <p>Conclusions</p> <p>These findings suggested that activation of the Hh pathway maybe associated with CML progression. Treatment of CML with imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase inhibitor, has no significant influence on the inhibition of Hh pathway of CML-CP patients.</p

Circulating tissue factor-positive procoagulant microparticles in patients with type 1 diabetes

Aim: To investigate the count of circulating tissue factor-positive (TF+) procoagulant microparticles (MPs) in patients with type 1 diabetes mellitus (T1DM). Methods: This case-control study included patients with T1DM and age and sex-matched healthy volunteers. The counts of phosphatidylserine-positive (PS+) MPs and TF(+)PS(+)MPs and the subgroups derived from different cell types were measured in the peripheral blood sample of the two groups using multicolor flow cytometric assay. We compared the counts of each MP between groups as well as the ratio of the TF(+)PS(+)MPs and PS(+)MPs (TF(+)PS(+)MPs/PS(+)MPs). Results: We recruited 36 patients with T1DM and 36 matched healthy controls. Compared with healthy volunteers, PS(+)MPs, TF(+)PS(+)MPs and TF(+)PS(+)MPs/PS(+)MPs were elevated in patients with T1DM (PS(+)MPs: 1078.5 +/- 158.08 vs 686.84 +/- 122.04/mu L, P &lt;0.001; TF(+)PS(+)MPs: 202.10 +/- 47.47 vs 108.33 +/- 29.42/mu L, P &lt;0.001; and TF(+)PS(+)MPs/PS(+)MPs: 0.16 +/- 0.04 vs 0.19 +/- 0.05, P = 0.004), mostly derived from platelet, lymphocytes and endothelial cells. In the subgroup analysis, the counts of total and platelet TF(+)PS(+)MPs were increased in patients with diabetic retinopathy (DR) and with higher HbA1c, respectively. Conclusion: Circulating TF(+)PS(+)MPs and those derived from platelet, lymphocytes and endothelial cells were elevated in patients with T1DM.De tre första författarna delar förstaförfattarskapet.</p

Glycated Haemoglobin A1c Variability Score Elicits Kidney Function Decline in Chinese People Living with Type 2 Diabetes

Our aim was to investigate the association of glycated haemoglobin A1c (HbA1c) variability score (HVS) with estimated glomerular filtration rate (eGFR) slope in Chinese adults living with type 2 diabetes. This cohort study included adults with type 2 diabetes attending outpatient clinics between 2011 and 2019 from a large electronic medical record-based database of diabetes in China (WECODe). We estimated the individual-level visit-to-visit HbA1c variability using HVS, a proportion of changes in HbA1c of ≥0.5% (5.5 mmol/mol). We estimated the odds of people experiencing a rapid eGFR annual decline using a logistic regression and differences across HVS categories in the mean eGFR slope using a mixed-effect model. The analysis involved 2397 individuals and a median follow-up of 4.7 years. Compared with people with HVS ≤ 20%, those with HVS of 60% to 80% had 11% higher odds of experiencing rapid eGFR annual decline, with an extra eGFR decline of 0.93 mL/min/1.73 m(2) per year on average; those with HVS > 80% showed 26% higher odds of experiencing a rapid eGFR annual decline, with an extra decline of 1.83 mL/min/1.73 m(2) per year on average. Chinese adults with type 2 diabetes and HVS > 60% could experience a more rapid eGFR decline

An Improved Predictive Model for Determining the Permeability Coefficient of Artificial Clayey Soil Based on Double T2 Cut-Offs

Permeability is one of the most important engineering properties of clayey soil. However, the traditional method for determining the permeability coefficient is time-consuming. To establish a simple and accurate predictive method to obtain the permeability coefficient of artificial clayey soil based on the double cut-off transverse relaxation times (T2 cut-offs) using low-field nuclear magnetic resonance (NMR) technology, eight kinds of artificial clayey soil with different mineralogical compositions were prepared in the laboratory. Evaporation tests at 40°C were carried out on the saturated artificial clayey soil samples in an oven. During the evaporation process, NMR tests were also performed on the artificial clayey soil every hour. The results showed that the evaporation process could be divided into three stages according to different evaporation rates: the constant rate stage (CRS), the falling rate stage (FRS), and the residual stage (RS). The water evaporated in the CRS and FRS was defined as the absolute movable water and the partially movable water, respectively. The water that could not evaporate in the RS was defined as the immovable water. Based on the cumulative signal amplitudes in the T2 spectrum corresponding to different kinds of water, the double T2 cut-offs were defined. On the basis of the double T2 cut-offs and T2 spectrum of the saturated sample, an improved Timur–Coates (TC) model was established. The prediction capability of the improved model was evaluated by finding the determination coefficient (R2), mean absolute error (MAE), and root-mean-square error (RMSE). Compared with the typical TC model, the prediction accuracy of the improved model was much higher. In addition, the relationships between the double T2 cut-offs and fractal dimension (D) of the T2 spectrum of saturated artificial clayey soil were also identified

A Distributed Simulation Backbone for Executing HLA-based Simulation over the Internet

With the increase in complexity of simulations, there is a growing need for accessing large amount of computing resource and data sets which could be geographically distributed. The Grid provides an infrastructure for collaborative resource sharing to execute large-scale applications. In this paper, we propose a framework for distributed simulation using the High Level Architecture (HLA) over the Grid