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OBJECTIVE@#To determine the types and frequency of deafness-related variants among 7875 newborns from Dongying area of Shandong Province.@*METHODS@#One hundred loci of 18 common deafness genes were subjected to semiconductor sequencing. Variant site, frequency and distribution of the variants were analyzed.@*RESULTS@#In total 552 deafness gene variants were detected among the 7875 newborns, which yielded a detection rate of 7.01%. Among these, common variant sites for GJB2, SLC26A4 and GJB3 genes were c.235delC, IVS7-2A>G and c.538C>T, respectively. The variant frequencies of matrilinear inheritance deafness genes MT-CO1, MT-RNR1, MT-TL1 and MT-TS1 were 0.38%, 0.25%, 0.1% and 0.01%, respectively. Four newborns were diagnosed with deafness, among which one had unilateral hearing loss. Analysis of the proportions of neonatal deafness-related variants in five counties of Dongying showed that the highest variant rate for the SLC26A4 gene compared with GJB2 was in Lijin county (51.76% vs. 40%), while the lowest was in Hekou county (30.77% vs. 56.41%).@*CONCLUSION@#The carrier rate of deafness-related variants in Dongying area is higher than other regions of China, which may be attributed to the increased types and variant sites covered by the semiconductor sequencing method compared with the chip method and time-of-flight mass spectrometry. Due to geographical and population aggregation factors, the proportion of deafness variants in the five counties of Dongying differed significantly. Above results may provide a guide for the prevention of congenital deafness in Dongying area.
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AIM:To investigate the molecular mechanism of nontypeable Haemophilus influenzae ( NTHi)-in-duced MUC5AC expression in the human airway NCI-H292 cells.METHODS:Bronchial epithelial NCI-H292 cells were cultured in vitro.The production of MUC5AC and matrix metalloproteinase 9 (MMP-9) after stimulation with NTHi was analyzed by enzyme-linked immunosorbent assay (ELISA).The enzymatic activity of MMP-9 was detected by gelatin zy-mography.In addition, the cells were pretreated with different inhibitors such as AG 1478, LY294002, DPI, NAC and GM6001 before stimulation, which specifically inhibit epidermal growth factor receptor (EGFR), phosphatiadylinositol 3-ki-nase (PI3K), NADPH oxidase, reactive oxygen species (ROS) and MMP-9, respectively, and then the production of MUC5AC or MMP-9 was determined.RESULTS:NTHi-stimulated NCI-H292 cells exhibited a time-dependent increase in MMP-9 secretion and activity .NTHi also increased the activity of Rac 1 and the production of ROS .Pretreatment of AG1478 and LY294002 decreased the Rac1 activity, and preincubation of DPI or Rac 1 inhibitor significantly abrogated ROS production.In addition, secretion of MMP-9 and the enzymatic activity was decreased by treatment of NAC and NSC23766.Furthermore, inhibition of the MMP-9 activity by GM6001 significantly inhibited MUC5AC production.CON-CLUSION:EGFR/PI3K/Rac1/NADPH oxidase/ROS/MMP-9 regulates MUC5AC production in NTHi-challenged NCI-H292 cells.
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Polo-box domain 1 (PBD1) is a characteristic domain of polo-like kinase 1 (PLK1), which locates in C-terminal and can influence the catalytic activity and specific subcellular locations of PLK1. At present, most PLK1 inhibitors are developed to occupy the ATP pocket or its close sites. However, this kind of PLK1 inhibitors is difficult to pursue target selectivity and may encounter cross drug resistance with other kinase inhibitors due to the conserved sequence of ATP pocket. Recently, PBD1, with aberrant specificity in sequence and structure, has attracted enormous interests as the alternative target to the discovery of corresponding inhibitors for anti-tumor drugs. The structure and function of PBD1 as well as the advances of its inhibitors are reviewed in this paper.