Objective:To study the influence of metformin and paclitaxel in the proliferation and apoptosis of human ovarian cancer SKOV3 cells in vitro, and to clarify the synergistic effect of metformin and paclitaxel. Methods:The ovarian cancer SKOV3 cells were divided into blank control group, different concentrations (0.01, 0.50, 1.00, 5.00, 10.00mmol·L-1) of metformin groups and combined treatment groups(metformin combined with paclitaxel with different concentrations).The inhibitory rates of proliferation of SKOV3 cells after treated with different concentrations of metformin were detected by MTT method.The apoptotic rates of SKOV3 cells after treated with different concentrations of metformin were measured by flow cytometry.The inhibitory rates of proliferation of SKOV3 cells after treated with metformin and paclitaxel were determined by MTT method.Results:The MTT results showed that the inhibitory rates of proliferation of SKOV3 cells in different concentrations of metformin groups were increased in concentration-and timedependent manner;there were significant differences compared with blank control group (P<0.05).The flow cytometry results showed that the apoptotic rates of SKOV3 cells in different concentrations of metformin groups were increased;compared with control group, with the increasing of concentrations of metformin, the apoptotic rates of SKOV3 cells in experimental groups 48 h after treatment were increased significantly (P<0.05);the percentages of SKOV3 cells in G0/G1 phase were decreased with the increasing of metformin concentrations(P<0.05) and the percentages of SKOV3 cells in G2/M phase were increased(P<0.05).The MTT results showed that the inhibitory rate of proliferation of SKOV3 cells in 1.00 mmol·L-1 metformin+paclitaxel group was higher than that in 0.50 mmol·L-1 metformin+paclitaxel group was higher than that in 0.50 mmol·L-1 metformin+paclitaxel group(P<0.05),and the inhibitory rates of proliferation of SKOV3 cells in combined treatment groups were higher than those in paclitaxel alone groups(P<0.05).Conclusion:Metformin inhibits the proliferation of ovarian cancer SKOV3 cells through the induction of apoptosis.Metformin can enhance the cell proliferation inhibition of paclitaxel on ovarian cancer SKOV3 cells.The combination of metformin and paclitaxel has a synergistic reaction on SKOV3 cells.

Objective: To explore the antagonistic effect of quercetin on fine particulate matter (PM2.5)-induced embryonic developmental toxicity in vitro.Methods: PM2.5 was collected on glass fiber filters by PM2.5 samplers during the heating period of Dec.2015 to Mar.2016 in an area of Haidian District, Beijing City.The sampled filters were cut into 1 cm×3 cm pieces followed by sonication.The PM2.5 suspension was filtered into a 10 cm glass dish through 8 layers of sterile carbasus and stored at-80 ℃ until freeze drying.Frozen PM2.5 suspension was dried by vacuum freeze-drying.In vitro post-implantation whole embryo culture was used in this study.Pregnant rats with 9.5 gestation days (GD) were killed by cervical dislocation and the uteri were removed into sterile Hank's solution.The embryos with intact yolk sacs and ecto placental cones were induced by PM2.5, and then subjected to intervention of quercetin at the doses of 0.1 μmol/L, 0.5 μmol/L, 1.0 μmol/L and 5.0 μmol/L, respectively.At the end of the 48 h culture period, the cultures were terminated, and all embryos were removed from the culture bottles and placed in prewarmed Hank's solution for evaluation.Morphological evaluation of the embryos was conducted under a stereomicroscope using the morphologic scoring system by Brown and Fabro.The mitochondrial reactive oxygen species (ROS) level was detected by FACSCalibur flow cyto-metry using MitoSOXTM Red staining.Results: An obvious antagonistic effect was achieved through querce-tin at the dose of 1.0 μmol/L, which could result in an increase of visceral yolk sac (VYS) diameter, crown-rump length and head length, somite number, and the differentiation of visceral yolk sac vascular vessels.The scores of allantois, flexion, heart, hind brain, midbrain, forebrain, auditory system, visual system, olfactory system, branchialarch, maxillary process, forelimb bud and hindlimb bud also revealed a significant increase and the relative mitochondrial ROS level of embryonic cells was significantly decreased when compared with PM2.5 group.Although quercetin at the doses of 0.1 μmol/L, 0.5 μmol/L, 5.0 μmol/L also exhibited protective effects against PM2.5-induced embryonic developmental toxicity, the protective effect was weaker when compared with the dose of 1.0 μmol/L.Conclusion: Quercetin at proper dose may be of great benefit for the development of embryos exposed to PM2.5 in the uterus of the rats.Quercetin provides an effective strategy for the prevention of PM2.5-induced embryonic developmental toxicity.Clearance of mitochondrial ROS may be one of its mechanisms.

Objective To analyze the expressions of osteopontin (OPN)and chemokine (CXC-subfamily)receptor 4 (CXCR4)in different ovarian tissues,and to explore the role of OPN and CXCR4 in occurrence,development and metastasis of human ovarian cancer.Methods The expressions of OPN and CXCR4 in normal ovarian tissue (n=20),benign ovarian epithelial tumor (n=20)and epithelial ovarian cancers tissues (n=40)were detected by immunohistochemical SP method,and the expression rates of OPN and CXCR4 in epithelial ovarian cancer tissue with different clinical characteristics were analyzed.Results The positive expressions rate of OPN in epithelial ovarian cancer tissue was significantly higher than those in normal ovarian tissue and benign ovarian tumor tissue, and there were significant differences in the positive expression rates of OPN between different pathological stages (G1 ,G2 ,G3 )of epithelial ovarian cancer (P <0.05).Meanwhile,the positive expression rate of OPN in Ⅲ-Ⅳepithelial ovarian cancer tissue was significantly higher than that in Ⅰ-Ⅱ epithelial ovarian cancer tissue (P <0.05). However,there were no significant differences of the positive expression rates of OPN among different histological types of epithelial ovarian cancer tissue (P >0.05).There was no positive expression of CXCR4 protein in normal ovarian tissue and benign ovarian tumor tissues , but there was positive expression in epithelial ovarian cancer tissue.Besides,the expressions of CXCR4 protein were not significantly different among different pathological grades,different clinical stages and different histological types (P > 0.05).Conclusion The OPN and CXCR4 expression levels are correlated with the degrees of malignancy in epithelial ovarian tumor,therefore the CXCR4 and OPN expression pathways may be the new targets for ovarian cancer therapy.

Objective To investigate the changes of serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration in patients with Graves' disease (GD) and its clinical significance. Methods Two hundred and sixty-nine patients with GD were enrolled in this study. Serum concentrations of thyroid hormones,TRAb, and NT-proBNP were measured. Results Serum NT-proBNP levels were positively associated with FT3(r=0.260, P<0.01), FT4(r=0.297,P<0.01) and heart rate (r=0.251, P<0.05) independent of age,sex and body mass index (BMI). The difference of serum NT-proBNP concentrations between newly-onset and treated patients existed (P<0.01) after the adjustment for thyroid hormone levels, age, sex and BMI. Serum FT4level exerted a significant impact on NT-proBNP level (P <0.01). Serum NT-proBNP increased even in patients with controlled thyroid function. Conclusion Serum NT-proBNP level in patients with GD increases with elevation of FT4 independent of sex, age and BMI. The measurement of serum NT-proBNP concentration appears to be helpful to monitor the alteration of vascular stiffness and fluid volume in GD patients, and may provide useful evidence for early intervention of cardiovascular disease induced by hyperthyroidism.

Objective To investigate the effects of the genetic polymorphisms in osteoporosis-related genes and the gene-gene interaction on bone mineral density (BMD) and osteoporotic fractures.Methods Thirty-nine single nucleotide polymorphism (SNP) sites in 23 genes that related to bone mineral density ( BMD ) and osteoporotic fractures were scanned in 683 Shanghai Han postmenopausal women.TaqMan SNP Genotyping Assay or Sequenom Mass ARRAY System were applied for genotyping analysis.The relation of these SNP sites with BMD and osteoporotic fractures were analyzed.Results Altogether,12 SNPs in 9 candidate genes ( rs7524102 and rs6696981 in ZBTB40 gene,rs9479055 in ESR1 gene,rs6993813,rs6469804,and rs11995824 in OPG gene,rs3736228 in LRP5 gene,rs1107748 in SOST gene,rs87938 in CTNNB1 gene,rs1366594 in MEF2C gene,rs7117858 in SOX6 gene,and rs10048146 in FOXL1 gene) were associated with BMD at lumbar spine(L1-L4) or total hip.In addition,rs11898505 in SPTBN1 gene was related to osteoporotic fractures ( OR 0.522,95％ CI 0.326-0.838,P =0.007 ).Gene-gene interaction involving rs1038304 in ESR1 gene,rs1366594 in MEF2C gene,and rs10048146 in FOXL1 gene was associated with osteoporotic fractures ( P =0.010 7 ).Conclusions ( 1 ) SNPs in gene ZBTB40,ESR1,OPG,LRP5,SOST,CTNNB1,MEF2C,SOX6,FOXL1,and SPTBN1 are associated with BMD of lumbar spine or total hip,as well as osteoporotic fractures.(2) Gene-gene interaction involving rs1038304,rs1366594,and rs10048146may contribute to the risk of osteoporotic fractures.

Gut microbiota provide enzymes and additional biochemical metabolic pathways for the host, which together with the host genome and the external environment, influence the body function. The composition of gut microbiota in infant is closely related to health in later life. However, it is influenced by many factors, including delivery mode, feeding pattern, prenatal diet, pregnancy psychology and antepartum antibiotic treatment. Vaginal delivery and breastfeeding is beneficial for shaping gut microbiota, while cesarean section and formula feeding would reduce the amount of gut dominant bacteria. In addition, inappropriate diet during pregnancy, prenatal stress and antepartum antibiotic treatment alters bacterial colonization of the gut in infant.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.