Objective To investigate the effects of zalcitabine(ddC),a mitochondrial DNA polymerase γ(POLG)inhibitor,on the migration,invasion,and to preliminarily explore mitochondrial biogenesis of human tri-ple-negative breast cancer MDA-MB-231 cells.Methods The effect of ddC on cell viability was detected using the MTT assay.The migration and invasion abilities of the cells were evaluated using the cell scratch and Transwell in-vasion assays.Cell apoptosis was determined using flow cytometry and a V-FITC/PI cell apoptosis detection kit.The protein expression of POLG,NADH dehydrogenase subunit Ⅰ(NADH1),NADH dehydrogenase subunit Ⅱ(NADH2),ATP synthase subunit 6(ATPase6),cytochrome c oxidase subunit Ⅰ(COX-1)and cytochrome c ox-idase subunit Ⅲ(COX-3)were determined using Western blot.The POLG mRNA level and mtDNA copy number were determined using qPCR.The mitochondrial content and ATP levels were determined using MitoTracker Green fluorescent probe staining and an ATP determination kit.MDA-MB-231 cells were transfected with pcDNA3.1-EG-FP-POLG plasmids to overexpress POLG.The inhibitory effects of ddC on cell migration and invasion were detected in POLG-overexpressed MDA-MB-231 cells.Results POLG expression was higher in MDA-MB-231 cells than in normal mammary epithelial cells(MCF-10A)(P＜0.01).ddC inhibited cell viability in a dose-dependent man-ner.ddC inhibited the migration(P＜0.01)and invasion(P＜0.01)of MDA-MB-231 cells;however,it dis-played no significant inhibitory effects on cell viability in normal mammary epithelial cells(MCF-10A)at the same concentration.ddC downregulated the protein(P＜0.01)and mRNA(P＜0.01)levels of POLG,reduced mtD-NA copy number(P＜0.01)and downregulated mtDNA-coded NADH1,NADH2,ATPase6,COX-1 and COX-3 protein expression(P＜0.01)in MDA-MB-231 cells.Furthermore ddC inhibited mitochondrial content(P＜0.01)and ATP(P＜0.01)levels in MDA-MB-231 cells.POLG overexpression increased the migration(P＜0.05)and invasion(P＜0.05)abilities of MDA-MB-231 cells,while ddC did not significantly inhibit the migra-tion and invasion abilities of MDA-MB-231 cells overexpressing POLG.Conclusion ddC downregulates POLG ex-pression in MDA-MB-231 cells and inhibits mitochondrial biogenesis and ATP levels,thereby inhibiting the migra-tion and invasion of MDA-MB-231 cells.

Objective:To explore the relationship between the maternal dietary patterns during pregnancy and the early childhood BMI change trajectory.Methods:The subjects were 1 241 pairs of pregnant women and their children in Ma'anshan maternal and infant health cohort. The food frequency questionnaire was used to collect the maternal diet data during pregnancy. The cohort children were followed up at birth, month 3, 6, 12, 18 and 24, respectively. The body height and weight data of the cohort children were collected. The principal component analysis was used to determine the categories of maternal dietary patterns during pregnancy, group-based multi-trajectory modeling was used to fit the early childhood BMI change trajectory, and the multiple classification logistic regression model was used to evaluate the relationship between the maternal dietary patterns during pregnancy and the early childhood BMI change trajectory.Results:The maternal dietary patterns during pregnancy included protein type, healthy type, vegetarian type, processing type and beverage type, which could explain 50.04% of the total dietary variation. Among them, the protein type, main dietary pattern, could explain 21.34% of the total dietary variation. The early childhood BMI change trajectory was from thinnish stature to average stature, then to mild obesity, accounting for 42.9%, 45.6% and 11.5% respectively. After controlling the potential confounding factors, it was found that there was a statistical correlation between healthy type and beverage type of maternal dietary patterns during pregnancy and early childhood BMI change trajectory ( P<0.05). Comparison of change trajectories between thinnish type and average stature type, children in the low-level group of healthy diet pattern tended to have a thinnish type change trajectory in early life ( OR=1.286, 95% CI: 1.002-1.651). Comparison of change trajectories between mild obesity type and average stature type, children in the high-level group of beverage diet pattern tended to have a mild obesity type change trajectory in early life ( OR=0.565, 95% CI: 0.342-0.935). The other dietary patterns had no statistical correlation with the early childhood BMI change trajectory. Conclusions:Maternal dietary patterns during pregnancy can affect the early childhood BMI change trajectory, and the low-level healthy type diet is an independent risk factor for thinnish type change trajectory, and the high-level beverage type diet is an independent risk factor for the mild obesity type change trajectory.

Objective: To explore the effect of hypoxia inducible factor 1α(HIF-1α)on tamoxifen resistance in breast cancer MCF-7,and to established a human breast cancer cell line(MCF-7/TR)with 4-hydroxy tamoxifen(4-OHT)resistance. Methods: 4-OHT was an active form of tamoxifenin vivo, resistant breast cancer cells MCF-7/TR were establishedin vitrousing 4-OHT. MTT assay was used to detect the effect of 4-OHT on the MCF-7 and MCF-7/TR cells, and the drug resistance multiple was detected. Western blot was used to detect the expression level of HIF-1α protein in MCF-7 and MCF-7/TR cells. The effects of HIF-1α inhibitor(LW6) or siRNA HIF-1α on MCF-7/TR cells and 4-OHT on MCF-7 cells treated with HIF-1α stabilizer(FG-4592) were detected by MTT and flow cytometry AV/PI staining. Results: The results showed that the MCF-7/TR was successfully constructed, and the drug resistance ratio was(5.56±0.80). Compared with MCF-7 cells, MCF-7/TR cells had higher expression of HIF-1α protein and it was up-regulated after tamoxifen treatment. After giving LW6 or silencing the expression of HIF-1α,the down-regulation of HIF-1α expression enhanced the inhibitory effect of 4-OHT on MCF-7/TR cells. After treatment of FG-4592, the expression level of HIF-1α in breast cancer cells MCF-7 was up-regulated, and hindered the inhibition effect of tamoxifen on MCF-7 cells. Conclusion The above results indicate that HIF-1α plays an important role in 4-OHT resistant breast cancer, and targeting HIF-1α may be an effective way to increase the sensitivity of MCF7/TR cells to tamoxifen.

Objective : To investigate the association between adiposity rebound and metabolic abnormalities in pre- schools． Methods : A prospective cohort study was designed on the basis of the Maanshan birth cohort． Venous blood samples were collected at 5 to 6 years of age to detect metabolic indicators．2022 children aged 0 to 6 years with ≥8 consecutive measurements were enrolled. χ2 test and Logistic regression model were used to analyze the data. Results : The detection rate of abnormal metabolism in preschool children was 16. 9% ，and the risk of meta- bolic abnormalities in preschool children with high BMI level at the AR time point and earlier AR time phase was 2. 59 and 1. 82 times that of the normal group respectively． Conclusion High AR level and earlier AR phase can increase the prevalence of metabolic abnormalities in preschool children.