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 identify the key genes and targeted protection methods affecting the survival of human islets. Methods Using bioinformatics method, the gene expression profile (GSE53454) was selected through screening and comparison from Gene Expression Omnibus(GEO) database. GEO2R tool was employed to screen the differentially expressed gene(DEG) between the human islets exposed (exposure group) and non-exposed (non-exposure group) to interleukin (IL)-1β and interferon (IFN)-γ for 24, 48 and 72 h, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape apps. Results A total of 69 up-regulated DEGs and 2 down-regulated DEGs were identified. GO analysis showed that during the biological process, DEGs were enriched in the aspects of virus defense and inflammatory response. In cellular components, DEGs were significantly enriched in extracellular space, outside plasma membrane and extracellular regions. Regarding molecular functions, DEGs were significantly enriched in chemokine activity and cytokine activity. KEGG analysis revealed that DEGs were mainly enriched in multiple signaling pathways, such as cytokine-cytokine receptor interaction, virus protein-cytokine and cytokine-receptor interaction, etc. Ten key genes (STAT1, CXCL10, IRF1, IL6, CXCL9, CCL5, CXCL11, ISG15, CD274, IFIT3) with high connectivity were selected by STRING analysis, all of which were significantly up-regulated in human islets exposed to IL-1β and IFN-γ. Six genes (STAT1, CXCL10, CXCL9, CXCL11, CCL5, IL6) were screened by KEGG enrichment analysis, mainly in Toll-like receptor signaling pathway. Conclusions STAT1, CXCL10, CXCL9, CXCL11, CCL5 and IL6 are the key genes affecting the survival of human islets, which are mainly enriched in Toll-like receptor signaling pathway and act as important targets for islet protection.

Normal human blood pressure has a unique "dipper type" rhythm, but various pathological factors will lead to abnormal nighttime blood pressure decline, seriously damage the target organs such as the heart, brain and kidneys, and significantly increase the incidence of cardiovascular events. Therefore, it is necessary to pay sufficient attention to rhythm disorder of blood pressure and intervene early. Modern Traditional Chinese Medicine (TCM) mostly understands the changes of rhythm of blood pressure from the view of the unity of nature and man, yin-yang theory and the theory of meridian flow, and study the syndrome distribution and TCM constitution law of rhythm disorder of blood pressure by combining TCM syndrome differentiation method and TCM constitution theory. TCM treatment can restore blood pressure rhythm and improve clinical symptoms and sleep quality of patients.

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 expression pattern of aryl hydrocarbon receptor (AhR) in mice peritoneal macrophages (PMs) after major trauma and analyze the effects of enhanced AhR expression on the inflammatory cytokine level and bactericidal ability after trauma.Methods:The experimental study method was used. Forty 6-8-week-old male C57BL/6J mice (the same mouse age, sex, and strain below) were divided into control group, post trauma hour (PTH) 2 group, PTH 6 group, and PTH 12 group according to the random number table (the same grouping method below), with 10 mice in each group. Mice in the latter 3 groups were constructed as severe trauma model with fracture+blood loss, while mice in control group were left untreated. The primary PMs (the same cells below) were extracted from the mice in control group, PTH 2 group, PTH 6 group, and PTH 12 group when uninjured or at PTH 2, 6, and 12, respectively. Then the protein and mRNA expressions of AhR were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction, respectively, and the gene expressions of AhR signaling pathway related molecules were analyzed by transcriptome sequencing. Twenty mice were divided into control group and PTH 6 group, with 10 mice in each group, and the PMs were extracted. The level of ubiquitin of AhR was detected by immunoprecipitation. Twelve mice were divided into dimethyl sulfoxide (DMSO) alone group, PTH 6+DMSO group, MG-132 alone group, and PTH 6+MG-132 group, with 3 mice in each group. After the corresponding treatment, PMs were extracted, and the protein expression of AhR was detected by Western blotting. Twenty mice were constructed as PTH 6 model. Then, the PMs were extracted and divided into empty negative control adenovirus (Ad-NC) group and AhR overexpression adenovirus (Ad-AhR) group. The protein expression of AhR was detected by Western blotting at 36 h after some PMs were transfected with the corresponding adenovirus. The rest cells in Ad-NC group were divided into Ad-NC alone group and Ad-NC+endotoxin/lipopolysaccharide (LPS) group, and the rest cells in Ad-AhR group were divided into Ad-AhR alone group and Ad-AhR+LPS group. The expressions of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell supernatant were detected by enzyme-linked immunosorbent assay at 12 h after the corresponding treatment ( n=6). Twenty mice were obtained to extract PMs. The cells were divided into control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group, and the intracellular bacterial load was detected by plate spread method after the corresponding treatment ( n=6). Data were statistically analyzed with one-way analysis of variance, least significant difference test, analysis of variance for factorial design, and independent sample t test. Results:Compared with 1.16±0.28 of control group, the protein expressions of AhR in PMs in PTH 2 group (0.59±0.14), PTH 6 group (0.72±0.16), and PTH 12 group (0.71±0.17) were all significantly decreased ( P<0.05). The overall comparison of the difference of AhR mRNA expression in PMs among control group, PTH 2 group, PTH 6 group, and PTH 12 group showed no statistical significance ( P>0.05). The AhR signaling pathway related molecules included AhR, AhR inhibitor, cytochrome P450 family member 1b1, cytochrome P450 family member 11a1, heat shock protein 90, aryl hydrocarbon receptor-interaction protein, and heat shock protein 70 interaction protein. The heat shock protein 90 expression of PMs in PTH 2 group was higher than that in control group, while the expressions of other molecules did not change significantly after trauma. Compared with that in control group, the level of ubiquitin of AhR in PMs in PTH 6 group was increased. Compared with that in DMSO alone group, the protein expression of AhR in PMs in PTH 6+DMSO group was decreased, while that in PMs in MG-132 alone group had no significant change. Compared with that in PTH 6+DMSO group, the protein expression of AhR in PMs in PTH 6+MG-132 group was up-regulated. At transfection hour 36, compared with that in Ad-NC group, the protein expression of AhR in PMs in Ad-AhR group was increased. At treatment hour 12, compared with those in Ad-NC+LPS group, the expressions of IL-6 and TNF-α in PM supernatant of Ad-AhR+LPS group were significantly decreased (with t values of 4.80 and 3.82, respectively, P<0.05). The number of intracellular bacteria of 1×10 6 PMs in control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group was (3.0±1.8), (41.8±10.2), (1.8±1.2), and (24.2±6.3) colony forming unit, respectively. Compared with that in PTH 6+Ad-NC group, the number of intracellular bacteria of PMs in PTH 6+Ad-AhR group was significantly decreased ( t=3.61, P<0.05). Conclusions:Ubiquitin degradation of AhR in PMs of mice after major trauma results in decreased protein expression of AhR. Increasing the expression of AhR in post-traumatic macrophages can reduce the expressions of LPS-induced inflammatory cytokines IL-6 and TNF-α, and improve the bactericidal ability of macrophages after trauma.

【Objective】 To explore the recruitment and retention strategy of blood donors by investigating the age composition of blood donors in some areas of China, so as to promote blood donation and enhance clinical blood supply. 【Methods】 Through the working platform of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions, the average age and age composition of blood donors from 22 blood centers were collected, and statistical analysis was conducted after eliminating invalid data. 【Results】 The median average age of blood donors during the survey year was 30.02.The median age in 2.89% of the blood centers was lower than 25. The average age of different genders was statistically significant only in 2018(P<0.05). Fot first-time blood donors, the median constituent ratio of donors <25 and ≥25 years old was 54.53% and 44.28%, with median retention rate at 10.30% and 9.61%, respectively. The median overall participation rate of blood donors was 2.7%, with median participation rate of blood donors <25 years old at 5.1%. 【Conclusion】 The recruitment and retention of blood donor is crucial to enhance clinical blood supply. Blood donors <25 years old, with a longer period for future donation, should be the main target of blood donation recruitment. Meanwhile, the revision of upper age limit for blood donation is another important initiative to grow the blood donor pool.

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 analyze the associations between prenatal and 1-year-old exposure to antibiotics and allergic symptoms in children aged 6-11 months and 18-23 months.Methods:In this study, a prospective birth cohort study was adopted. A total of 2 122 pregnant women were enrolled in Maternal and Child Health Care Center of Ma′anshan from June 2015 to June 2016, and they were followed up from the beginning of pregnancy to children′s 24 months of age. Excluding 564 pairs of mothers and children who were lost to follow-up or with incomplete information on the use of antibiotics and children′s allergic symptoms, a total of 1 558 pairs of mothers and children were included in the analysis of this study. The parents and children′s general demographic information, early-life antibiotic exposure and other data were collected, the information about allergic symptoms in children aged 6-11 months and 18-23 months were investigated by reference to the "International Study of Asthma and Allergies in Childhood (ISAAC)". The univariate and multivariate binary unconditional logistic regression model was used to was used to estimate associations between the effects of early-life antibiotic exposure on allergic symptoms in 2-year-old children.Results:The antibiotic usage rate of pregnant women during pregnancy was 3.4% (53), and the antibiotic usage rates of children between 0 to 2 months, 3 to 5 months, and 6 to 11 months were separately 15.2%(237), 15.5%(242) and 17.3%(269). The total prevalence of allergic diseases in children aged 6 to 11 months was 24.1% (375 children), and the total prevalence of allergic diseases in children aged 18 to 23 months was 22.0% (342 children). After adjust parental (maternal) education level, family monthly income per capita, parental (maternal) allergy history, parental (maternal) age at pregnancy, mother′s Body Mass Index (BMI) before pregnancy, exposure to second-hand smoke during pregnancy, delivery method, child gender, birth weight, preterm birth, the use of antibiotics when children were 3-5 months old ( RR=1.61,95% CI:1.19-2.17) and 6-11 months old ( RR=1.43,95% CI:1.06-1.93) were the risk factors for allergic symptoms at 6-11 months of age; and the use of antibiotics when children were 0-2 months old (RR=1.41, 95% CI: 1.03-1.95), 3-5 months old ( RR=1.54, 95% CI: 1.12-2.11) and 6-11 months old ( RR=1.58, 95% CI: 1.17-2.14) were the risk factors for allergic symptoms at 18-23 months of age. Conclusion:Children′s exposure to antibiotics within 1 year of age was a risk factor for allergic symptoms in children aged 6-11 months and 18-23 months, children should avoid unnecessary antibiotic use in infancy.

Objective:To investigate the association of thallium exposure during pregnancy with pregnant blood pressure changing and hypertensive disorder complicating pregnancy(HDCP).Methods:A total of 3 240 pregnant women who had establish maternal health care manual in Ma′anshan Maternal and Child Health-Care Hospital and met the inclusion and exclusion criteria were included in this study between May 2013 and September 2014.We collected their general demographic characteristics and blood pressure through questionnaire and medical records. Meanwhile we measured serum thallium concentrations by experimental technology. We use multiple logistic regression to analyze the association between thallium exposure during pregnancy and HDCP. Mixed linear model were used to analyze the association between thallium concentration and maternal systolic blood pressure (SBP) or diastolic blood pressure(DBP) in different trimestersResults:The age of 3 240 pregnant woman was (26.61±3.64) years, and the detection rate of HDCP was 5.9%(191).The median ( P 25, P 75) of thallium concentrations in first trimester, second trimester and third trimester were 62.96 (50.79, 77.04), 62.19 (50.87, 75.26), 48.84 (38.00, 66.00) ng/L, respectively. Multiple logistic regression results suggested after adjusting various confounding factors, the risk of HDCP in pregnant women with high concentrations of thallium (>77.04 ng/L) in the first trimester is 1.75 (95% CI:1.01-3.03) times higher than which with low concentrations(<50.82 ng/L). Mixed linear model results suggested there are positive correlation between thallium concentrations with maternal DBP in first trimester (β=1.12, 95% CI: 0.39-1.85). Conclusion:Exposure to high levels of thallium during first trimester may increase the risk of HDCP, and the exposure of thallium may be effective to DBP of pregnant.

Objective:To analyze the associations between prenatal and 1-year-old exposure to antibiotics and allergic symptoms in children aged 6-11 months and 18-23 months.Methods:In this study, a prospective birth cohort study was adopted. A total of 2 122 pregnant women were enrolled in Maternal and Child Health Care Center of Ma′anshan from June 2015 to June 2016, and they were followed up from the beginning of pregnancy to children′s 24 months of age. Excluding 564 pairs of mothers and children who were lost to follow-up or with incomplete information on the use of antibiotics and children′s allergic symptoms, a total of 1 558 pairs of mothers and children were included in the analysis of this study. The parents and children′s general demographic information, early-life antibiotic exposure and other data were collected, the information about allergic symptoms in children aged 6-11 months and 18-23 months were investigated by reference to the "International Study of Asthma and Allergies in Childhood (ISAAC)". The univariate and multivariate binary unconditional logistic regression model was used to was used to estimate associations between the effects of early-life antibiotic exposure on allergic symptoms in 2-year-old children.Results:The antibiotic usage rate of pregnant women during pregnancy was 3.4% (53), and the antibiotic usage rates of children between 0 to 2 months, 3 to 5 months, and 6 to 11 months were separately 15.2%(237), 15.5%(242) and 17.3%(269). The total prevalence of allergic diseases in children aged 6 to 11 months was 24.1% (375 children), and the total prevalence of allergic diseases in children aged 18 to 23 months was 22.0% (342 children). After adjust parental (maternal) education level, family monthly income per capita, parental (maternal) allergy history, parental (maternal) age at pregnancy, mother′s Body Mass Index (BMI) before pregnancy, exposure to second-hand smoke during pregnancy, delivery method, child gender, birth weight, preterm birth, the use of antibiotics when children were 3-5 months old ( RR=1.61,95% CI:1.19-2.17) and 6-11 months old ( RR=1.43,95% CI:1.06-1.93) were the risk factors for allergic symptoms at 6-11 months of age; and the use of antibiotics when children were 0-2 months old (RR=1.41, 95% CI: 1.03-1.95), 3-5 months old ( RR=1.54, 95% CI: 1.12-2.11) and 6-11 months old ( RR=1.58, 95% CI: 1.17-2.14) were the risk factors for allergic symptoms at 18-23 months of age. Conclusion:Children′s exposure to antibiotics within 1 year of age was a risk factor for allergic symptoms in children aged 6-11 months and 18-23 months, children should avoid unnecessary antibiotic use in infancy.