ABSTRACT
@#In recent years, clear aligner technology has been maturing and is rapidly gaining popularity in the orthodontic market for its aesthetic and removable properties. However, despite the background of its large-scale clinical application, mechanical properties of clear aligners need to be studied in depth. This paper reviews the factors influencing mechanical properties of clear aligners and the current status of research to provide evidence-based guidance for clinical application.
ABSTRACT
Objective:To investigate the expression of miR-211-5p in peripheral blood of patients with myelosuppression after neoadjuvant chemotherapy for breast cancer and its effect on Notch signaling pathway by targeting cyclooxygenase 2 (COX2) gene Regulation mechanism.Methods:From Jan. 2018 to Jan. 2021, 185 breast cancer patients who received neoadjuvant chemotherapy in Linyi People’s Hospital for the first time were included as the research objects. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the mRNA expression levels of miR-211-5p, COX2 gene and Notch signaling pathway related genes (Notch1, Jagged1 and Hes1) . The miR-211-5p mimic, inhibitor, mimic NC, and inhibitor NC were transfected into SD rat bone marrow mesenchymal stem cells, and the mRNA expression of miR-10a-3p and COX2 genes was detected by qRT-PCR for 48 hours. Western blot method was used to detect the protein expression levels of Notch signaling pathway related genes.Results:The relative expression of miR-211-5p in patients with severe myelosuppression was 2.41±0.32, which was significantly higher than that in patients with mild myelosuppression (1.53±0.18) ( t=6.385, P<0.001) ; The relative expression of COX2 gene mRNA in patients with severe myelosuppression was 3.64±0.74, which was significantly lower than that in patients with mild myelosuppression (5.37±1.02) ( t=7.469, P<0.001) . In patients with severe myelosuppression, there was a significant negative correlation between miR-211-5p and COX2 gene mRNA levels ( r=-0.694, P=0.006) . The results of the dual luciferase report experiment confirmed that COX2 was the target gene of miR-211-5p. The relative expression of Notch1, Jagged1, and Hes1 mRNA in peripheral blood of patients with severe myelosuppression were 2.35±0.41, 2.76±0.46 and 3.04±0.52, respectively, which were significantly lower than those in patients with mild myelosuppression (4.12±0.63, 4.53±0.58 and 5.12±0.67) ( t=5.367, 6.114 and 6.135, respectively, P<0.001) . After transfecting SD rat bone marrow mesenchymal stem cells with miR-211-5p mimics and inhibitors, the relative expression of miR-211-5p in the mimic group was 3.46±0.49, significantly higher than that in the mimic NC group (2.24±0.32) The relative expression of miR-211-5p in the inhibitor group was (1.28±0.19) and (2.33±0.37) inhibitor NC group ( P<0.001) , while the relative expression of miR-211-5p in the inhibitor group was significantly lower than that in the other three groups ( P<0.001) . The mRNA expression of COX2 gene in mimic group was 2.73±0.36, which was significantly lower than that in mimic NC group (4.05±0.59) , inhibitor group (6.15±0.86) and inhibitor NC group (4.18±0.65) ( P<0.001) , while mRNA expression of COX2 gene in the inhibitor group was significantly higher than that in the other three groups ( P<0.001) . The expression of Notch1, Jagged1, and Hes1 in the inhibitor group was significantly increased, while the expression of Notch1, Jagged1, and Hes1 in the mimic group was significantly decreased. Conclusion:The expression level of miR-211-5p in peripheral blood of severe myelosuppressed patients with breast cancer after neoadjuvant chemotherapy is significantly increased, and the Notch signaling pathway can be inhibited by targeted down-regulation of COX2 gene expression.
ABSTRACT
Objective:To investigate the effects of two SNP sites of delta-like ligand protein-1 (DLL1) gene rs2738822 (C>T) and rs9459988 (T>G) and gene expression on bone marrow suppression after neoadjuvant chemotherapy for breast cancer.Methods:Breast cancer patients who received neoadjuvant chemotherapy were selected as study subjects, including 90 patients with severe bone marrow suppression and 72 patients with mild bone marrow suppression. Patient’s demographic characteristics and laboratory test indicators were collected. Two SNP sites of DLL1, rs2738822 and rs9459988, were genotyped by capillary electrophoresis and section analysis (SNaPshot) . The relative mRNA expression of DLL1 gene was detected by quantitative reverse polymerase chain reaction (QRT-PCR) method.Results:For The rs2738822 of DLL1 gene, the genotype distribution difference between severe and mild bone marrow suppression groups was statistically significant ( χ2=8.622, P=0.013) . Compared with CC genotype, CT and TT genotype carriers had a higher risk of severe bone marrow suppression, with an OR value of 2.746 (1.335-6.882) and 3.054 (1.282-8.143) , respectively. The dominant model results showed that TT OR CT carriers had a significantly higher risk of severe bone marrow suppression than THOSE with CC genotype [ OR=2.976 (1.231-4.963) ]. For rs9459988, there was no significant difference in genotype distribution between severe bone marrow suppression group and mild bone marrow suppression group ( χ2=2.149, P=0.342) . Results of the dominant model showed that TG or GG carriers had a significantly higher risk of severe bone marrow suppression than TT carriers, with an OR value of 2.046 (1.053-5.611) . The relative mRNA expression level of DLL1 gene was 1.15±0.23 in patients with severe bone marrow suppression, which was significantly lower than that in patients with mild bone marrow suppression (2.64±0.51) ( t=6.381, P<0.001) . For rs2738822, with the increase of T allele, the relative mRNA expression level of DLL1 gene decreased gradually ( P<0.05) . For rs9459988, the relative mRNA expression level of DLL1 gene in patients with mutant allele G was also significantly lower than that in wild-type CC carriers ( P<0.05) . Conclusion:Mutations of DLL1 genes rs2738822 and rs9459988 are related to the occurrence of severe bone marrow suppression after neoadjuvant chemotherapy for breast cancer, and can be used as a genetic marker to predict the degree of bone marrow suppression after neoadjuvant chemotherapy for breast cancer patients.