Objective To investigate acoustic characteristics of VC coarticulation for males in Mandarin . Methods This study compared nasal flow of 32 male adults'production which include /an/,/in/,/?n/,/a?/,/i?/,/??/,/a/,/i/,/?/.Results Whether /a /,/i/or /?/,the nasal flow of vowels before /n/was greater than the na-sal flow of vowels before /?/was greater than the nasal flow of vowels themselves .When produced solely ,the na-sal flow of /i/was greater than the nasal flow of /a/,/?/ .Before nasal consonants /n/,/?/ ,the nasal flow of /i/was greater than the nasal flow of /?/which was greater than the nasal flow of /a/.Conclusion Vowels before nasal consonants can be nasalized .The nasalization of /n/to vowel is greater than that of /?/to vowel .When nasals is produced around ,the nasalization of vowel depends on the height of the tongue .The nasal flow of vowels can be used as an effective measure and monitor the indicators before and after nasal coarticulatin .

Objective To analyze implanted children's production of vowels and to investigate the features of vowels production .Methods Thirty CI children averaged 32 .65 ± 5 .97 months were enrolled in this study .Using 19 Chinese vowels as test materials ,accuracy rates were statistically analyzed to get the difficulty gradient and main error patterns .Results /a/and /e/were the easiest vowels and /üe/,/uai/,/ü/were the most difficult vowels for CI children .From the mouth shape of vowels ,the difficulty gradients from easy to difficult were open -mouths →e-ven-teeth → close-mouths → pursed -mouths .From the structures of vowels ,triphthongs were the most diffi-culty ,while single vowels and diphthongs shared the same difficulty level .High vowel's nasalization ,the deletion of diphthongs and triphthongs ,the separation of diphthongs and triphthongs and the substitution of /o/,/ü/,and /ai/were the main error patterns .Conclusion The difficulty levels of vowels'production for CI children at average age of 31 months are rather obvious .Compared with aided children ,they show some common developmental sequences and error patterns ,but also reflect their own characteristics .When in vowel articulation therapy for little CI children ,we should provide targeted training according to error patterns on the basis of following their sequences of difficulty level to fa-cilitate their efficiency .

Objective:To explore the effects of BCR-ABL downstream pathway inhibitors, such as RAF inhibitor SB590885, JAK inhibitor AZD1480, PI3K-mTOR double target inhibitor BEZ235 on chronic myelogenous leukemia (CML) cells, and the effect of BEZ235 on the proliferation, apoptosis of CML cells and the sensitivity of imatinib in vitro.Methods:K562 cells were treated with different concentrations of the drugs. MTS method was applied to detect the proliferation inhibition rate of K562 cells, and 50% inhibitory concentration (IC 50) of all drugs for 48 h was calculated. The cell apoptosis rate was tested by using flow cytometry with Annexin V-FITC/PI double staining. The cell cycle was tested by using flow cytometry with PI staining. K562 cells, imatinib-resistant and T315I-mutant human CML KBM7R cells and imatinib-resistant CML primary cells of patients were treated with different concentrations of the drugs. MTS method was used to test the proliferation inhibition of cells, and IC 50 of all drugs for 48 h was evaluated. KBM7R cells or primary cells of CML patients were treated with 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib or the combination of both, respectively. Flow cytometry with PI staining was used to detect the cell cycle of KBM7R cells. Flow cytometry with Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate in CML primary cells. The expressions of p-AKT, cleaved Caspase-3 and Cyclin D1 proteins were detected by using Western blot. Results:SB590885, AZD1480 and BEZ235 could inhibit the proliferation of K562 cells, and the IC 50 after the treatment of K562 cells for 48 h was (11.49±3.14), (4.83±1.26) and (0.37±0.21) μmol/L, respectively. SB590885, AZD1480 and BEZ235 could promote the apoptosis of K562 cells. The cell apoptosis rates were increased compared with the control group without drug treatment (all P < 0.01). SB590885 and BEZ235 induced G 0/G 1 block (both P < 0.05). AZD1480 induced G 2/M block ( P < 0.05). BEZ235 could inhibit the proliferation of K562 cells, KBM7R cells and CML primary cells, and their IC 50 for 48 h was (0.37±0.21), (0.43±0.27) and (0.49±0.24) μmol/L, respectively. Compared with imatinib alone, the different concentrations of imatinib combined with 0.2 μmol/L BEZ235 could increase the proliferation inhibition of K562 cells, KBM7R cells and CML primary cells, and could reduce the IC 50 of imatinib. After the treatment of imatinib alone and combination with BEZ235 for 48 h, the imatinib IC 50 of K562 cells was (0.14±0.05) and (0.09± 0.04) μmol/L ( t = 1.531, P = 0.249), the imatinib IC 50 of KBM7R cells was (3.93±2.29) and (0.44±0.22) μmol/L ( t = 2.837, P = 0.047), the imatinib IC 50 of the primary cells was (3.12±1.53) and (0.39±0.23) μmol/L ( t = 3.925, P = 0.042). The cell apoptotic rate of the primary cells was (4.9±1.4)%, (13.1±3.2)%, (8.8±2.0)% and (40.6±6.0)%, respectively in the control group without drug treatment, 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib and the combination of 1.0 μmol/L BEZ235 and 1.0 μmol/L imatinib after the treatment of 24 h ( F = 71.031, P < 0.01). Compared with imatinib alone, the expressions of p-AKT and Cyclin D1 proteins were decreased, and the expression of cleaved Caspase-3 protein was increased after the treatment of KBM7R cells for 12 h in the combination group of both BEZ235 and imatinib. Conclusions:BCR-ABL downstream pathway inhibitors can effectively inhibit the proliferation and promote the apoptosis of K562 cells. BEZ235 can inhibit the proliferation and promote the apoptosis of K562 cells, imatinib-resistant and T315I-mutant human KBM7R cells and imatinib-resistant CML primary cells of patients, which has a synergistic effect to imatinib.