[Efficacy of Tyrosine Kinase Inhibitor Combined with Decitabine, Homoharringtonine, Interferon in the Maintenance Therapy of Blast Phase Chronic Myeloid Leukemia].

OBJECTIVE: To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP). METHODS: The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test. RESULTS: A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group. CONCLUSION: The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.

Effect of oxygen partial pressure on the performance of homojunction amorphous In-Ga-Zn-O thin-film transistors.

In this study, the homojunction thin-film transistors (TFTs) with amorphous indium gallium zinc oxide (a-IGZO) as active channel layers and source/drain electrodes were fabricated by RF magnetron sputtering. The effect of oxygen partial pressure on the phase, microstructure, optical and electrical properties of IGZO thin films was investigated. The results showed that amorphous IGZO thin films always exhibit a high transmittance above 90% and wide band gaps of around 3.9 eV. The resistivity increases as the IGZO thin films are deposited at a higher oxygen partial pressure due to the depletion of oxygen vacancies. In addition, the electrical behaviors in homojunction IGZO TFTs were analyzed. When the active channel layers were deposited with an oxygen partial pressure of 1.96%, the homojunction IGZO TFTs exhibited optimal transfer and output characteristics with a field-effect mobility of 13.68 cm2V-1s-1. Its sub-threshold swing, threshold voltage and on/off ratio are 0.6 V/decade, 0.61 V and 107, respectively.

Apelin­13 ameliorates LPS­induced BV­2 microglia inflammatory response through promoting autophagy and inhibiting H3K9ac enrichment of TNF­α and IL­6 promoter.

Microglia is activated and polarized to pro­inflammatory M1 phenotype or anti­inflammatory M2 phenotype in neuroinflammation. Apelin­13 exerts protective properties against neuroinflammation in several neurological disorders. We aimed to investigate whether apelin­13 played a protective role on BV­2 microglia and explore its underlying mechanisms. Lipopolysaccharide (LPS)­stimulated BV­2 microglia cells were treated with apelin­13. Microglia activation was evaluated by immunofluorescence with F­actin. Western blot was performed to measure the expression of autophagy associated proteins. CD16/32 and CD206 were detected to assess microglia polarization by western blot and flow cytometry. qRT­PCR was utilized to measure inducible nitric oxide synthase (iNOS), arginase­1 (Arg­1), interleukin­10 (IL­10), interleukin­6 (IL­6) and tumor necrosis factor­alpha (TNF­α). Histone H3 acetyl lysine 9 (H3K9ac) enrichment of TNF­α and IL­6 promoter was detected by ChIP. We discovered that apelin­13 impacted the actin cytoskeleton, recovering the control phenotype following LPS exposure. Apelin­13 improved autophagy­mediated microglia polarization towards M2 phenotype to alleviate inflammatory response in LPS­stimulated cells. Autophagy flux inhibitor chloroquine antagonized these effects of apelin­13 on LPS­stimulated cells. Besides, apelin­13 decreased the enrichment of H3K9ac at the promoter region of TNF­α and IL­6 to inhibit inflammatory response, which was reversed by histone deacetylase antagonist valproate. Taken together, apelin­13 alleviated inflammation via facilitating microglia M2 polarization due to autophagy promotion, and inhibiting H3K9ac enrichment on promoter regions of TNF­α and IL­6.

In-Sn-Zn Oxide Nanocomposite Films with Enhanced Electrical Properties Deposited by High-Power Impulse Magnetron Sputtering.

In-Sn-Zn oxide (ITZO) nanocomposite films have been investigated extensively as a potential material in thin-film transistors due to their good electrical properties. In this work, ITZO thin films were deposited on glass substrates by high-power impulse magnetron sputtering (HiPIMS) at room temperature. The influence of the duty cycle (pulse off-time) on the microstructures and electrical performance of the films was investigated. The results showed that ITZO thin films prepared by HiPIMS were dense and smooth compared to thin films prepared by direct-current magnetron sputtering (DCMS). With the pulse off-time increasing from 0 µs (DCMS) to 2000 µs, the films' crystallinity enhanced. When the pulse off-time was longer than 1000 µs, In2O3 structure could be detected in the films. The films' electrical resistivity reduced as the pulse off-time extended. Most notably, the optimal resistivity of as low as 4.07 × 10-3 Ω·cm could be achieved when the pulse off-time was 2000 µs. Its corresponding carrier mobility and carrier concentration were 12.88 cm2V-1s-1 and 1.25 × 1020 cm-3, respectively.

The associations of CYP19A1 rs700518 polymorphism with bone mineral density and risk of osteoporosis: a meta-analysis.

Osteoporosis is now a worldwide public health problem that seriously endangers human health, but its causes have not yet been fully clarified. Recently, increasing evidence suggested that polymorphisms in CYP19A1 gene were associated with osteoporosis risk and bone mineral density (BMD), but results remained conflicting. We herein performed a meta-analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. The PubMed, Embase, Cochrane library, CNKI (China National Knowledge Infrastructure), and Wan Fang databases were searched for eligible studies. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were applied to assess the strength of these relationships. A total of 8 studies involving 2632 subjects were included in our meta-analysis. We observed that the AG genotype of CYP19A1 rs700518 was significantly associated with lower BMD values of lumbar spine and femoral neck (AG vs. GG: p = .001 and.01, respectively). However, this polymorphism had no obvious impacts on osteoporosis risk according to current available data. In conclusion, the present meta-analysis showed that CYP19A1 rs700518 polymorphism may be a potential candidate biomarker for osteoporosis screening, early diagnosis, and treatment, which will help improve individualized therapy of osteoporosis patients in clinics.

Enhancement of miR-16-5p on spinal cord injury-induced neuron apoptosis and inflammatory response through inactivating ERK1/2 pathway.

BACKGROUND: To explore the effect and mechanism of miR-16-5p on neuron apoptosis and inflammatory response induced by spinal cord injury (SCI). METHODS: Allen's weight-drop method and Basso Bcattie Bresnahan (BBB) rating scale were used to establish SCI rat model and assess locomotor function, respectively. Histopathology of SCI rats and Sham-operated rats was validated by hematoxylin and eosin (H&E) staining. After intravenous injection of miR-16-5p agomir, miR-16-5p antagomir, pcDNA3.1-Apelin-13 or negative controls into SCI rat tails, neuron apoptosis and the expression of miR-16-5p, Apelin-13, apoptotic proteins, inflammatory response-related proteins and ERK1/2 pathway-related protein were detected. Dual luciferase reporter gene assay was applied for identifying the binding between miR-16-5p and Apelin-13. RESULTS: SCI rats had locomotor impairment with markedly edema and hemorrhage. Upregulated miR-16-5p expression and downregulated Apelin-13 expression were presented in SCI rats. Intravenous injection of miR-16-5p antagomir or/and pcDNA3.1-Apelin-13 could increase the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1) and p-ERK1/2 expression while decrease the expression of pro-apoptotic proteins (cleaved caspase-3 and Bax) and inflammatory response-related proteins (TNF-α, IL-1ß and IL-6). The reverse pattern was shown in rats injected with miR-16-5p agomir. MiR-16-5p targeted Apelin-13. Promotion of miR-16-5p agomir on SCI was attenuated by injection of agomir + pcDNA3.1-Apelin-13. CONCLUSIONS: Downregulation of miR-16-5p could upregulate Apelin-13 expression to activate ERK1/2 pathway, thus alleviating SCI-induced neuron apoptosis and inflammatory response.

Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury.

A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-µm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.