Epidemiology of Birth Defects in Eastern China and the Associated Risk Factors.

BACKGROUND This study aimed to survey the overall situation of birth defects (BDs) among citizens of Hangzhou, China, and the risk factors of different BD types. MATERIAL AND METHODS We collected the data of 4349 perinatal infants with BDs in Hangzhou. The potentially associated risk factors of BDs were recorded and logistic regression analysis was used to predict the high incidence of BDs. RESULTS Among all perinatal infants with BDs, there were 4105 (94.3%) single births, 225 (5.2%) twin births, and 10 (0.2%) multiple births. In clinical outcomes, there were 2477 (57.0%) live births, 1806 (41.5%) dead fetuses, and 11 (0.3%) stillbirths. Down syndrome ranked first, accounting for 30.7% of the total births, followed by cleft lip and polydactyly. Low family income, nulliparity, high parity, high education level, and taking contraceptives in early pregnancy were found to be risk factors of Down syndrome. Low parity, low education level, and pesticide exposure were found to be risk factors of cleft lip. For polydactyly, young age of the mother and a parity above 0 were identified as risk factors. CONCLUSIONS Different risks factors can influence BD development and potentially help to predict specific BD types, such as demographic features and harmful exposure in early pregnancy.

Functional study of the upregulation of miRNA-27a and miRNA-27b in 3T3-L1 cells in response to berberine.

Berberine is the major active component of Rhizoma Coptidis derived from a traditional Chinese herbal medicine and is known to regulate micro (mi)RNA levels, although the mechanism for this action remains unknown. The present study confirmed that treatment of 3T3­L1 cells with berberine inhibited cell viability and differentiation in a dose­ and time­dependent manner, and significantly increased the mRNA expression levels of miRNA­27a and miRNA­27b. In addition, in 3T3­L1 cells treated with berberine, overexpression of miRNA­27a and miRNA­27b improved the berberine-mediated inhibition of cell differentiation and reduction of triglyceride contents. By contrast, miRNA­27a and miRNA­27b inhibitors attenuated the berberine­mediated inhibition of cell differentiation and reduction of triglyceride contents. Additionally, peroxisome proliferator­activated receptors (PPAR)­Î³ was confirmed to be a target of miRNA­27a in the 3T3­L1 cells. A dual­luciferase reporter assay indicated that the expression of PPAR­Î³ was negatively regulated by miRNA-27a. These findings may provide novel mechanistic insight into the antiobesity effects of certain compounds in traditional Chinese herbal medicine.

Protective effects of berberine on high fat-induced kidney damage by increasing serum adiponectin and promoting insulin sensitivity.

Berberine (BBR) has been reported in several studies in cell and animal models. However, the mechanism of actions is not fully understood. The present study was therefore aimed to explore the effects of berberine on insulin sensitivity and kidney damage in a high fat diet rat model. Impaired glucose tolerance rats induced by injection of berberine while fed with high fat laboratory chow. After rats were treated for 4 weeks, OGTT and IPITT were determined. Mass and PAS were used to study the kidney tissue. ELISA was used to detect the protein concentration of CRP and TNF-α. Western blot was used to detect the proteins adiponectin, adipoR1, adipoR2 and p-AMPK expression level. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent kidney damage.

Knocking down 10-Formyltetrahydrofolate dehydrogenase increased oxidative stress and impeded zebrafish embryogenesis by obstructing morphogenetic movement.

BACKGROUND: Folate is an essential nutrient for cell survival and embryogenesis. 10-Formyltetrahydrofolate dehydrogenase (FDH) is the most abundant folate enzyme in folate-mediated one-carbon metabolism. 10-Formyltetrahydrofolate dehydrogenase converts 10-formyltetrahydrofolate to tetrahydrofolate and CO2, the only pathway responsible for formate oxidation in methanol intoxication. 10-Formyltetrahydrofolate dehydrogenase has been considered a potential chemotherapeutic target because it was down-regulated in cancer cells. However, the normal physiological significance of 10-Formyltetrahydrofolate dehydrogenase is not completely understood, hampering the development of therapeutic drug/regimen targeting 10-Formyltetrahydrofolate dehydrogenase. METHODS: 10-Formyltetrahydrofolate dehydrogenase expression in zebrafish embryos was knocked-down using morpholino oligonucleotides. The morphological and biochemical characteristics of fdh morphants were examined using specific dye staining and whole-mount in-situ hybridization. Embryonic folate contents were determined by HPLC. RESULTS: The expression of 10-formyltetrahydrofolate dehydrogenase was consistent in whole embryos during early embryogenesis and became tissue-specific in later stages. Knocking-down fdh impeded morphogenetic movement and caused incorrect cardiac positioning, defective hematopoiesis, notochordmalformation and ultimate death of morphants. Obstructed F-actin polymerization and delayed epiboly were observed in fdh morphants. These abnormalities were reversed either by adding tetrahydrofolate or antioxidant or by co-injecting the mRNA encoding 10-formyltetrahydrofolate dehydrogenase N-terminal domain, supporting the anti-oxidative activity of 10-formyltetrahydrofolate dehydrogenase and the in vivo function of tetrahydrofolate conservation for 10-formyltetrahydrofolate dehydrogenase N-terminal domain. CONCLUSIONS: 10-Formyltetrahydrofolate dehydrogenase functioned in conserving the unstable tetrahydrofolate and contributing to the intracellular anti-oxidative capacity of embryos, which was crucial in promoting proper cell migration during embryogenesis. GENERAL SIGNIFICANCE: These newly reported tetrahydrofolate conserving and anti-oxidative activities of 10-formyltetrahydrofolate dehydrogenase shall be important for unraveling 10-formyltetrahydrofolate dehydrogenase biological significance and the drug development targeting 10-formyltetrahydrofolate dehydrogenase.

[Effect of long-term sevoflurane anesthesia on markers of myocardial damage].

OBJECTIVE: To investigate the effect of long-term sevoflurane anesthesia on markers of myocardial damage or toxicity. METHODS: Forty adult patients scheduled for upper abdominal surgery with general anesthesia for 4 hours or more were randomly divided into Group S and PR (n=20 each). After anesthesia induction, patients of Group S were maintained with only sevoflurane, and patients of Group PR with target-controlled infusion of propofol 2-4 microg/ml and remifentanil 4-8 ng/ml. Anesthesia was titrated to control blood pressure and heart rate change at less than 20 percent of baseline values. Blood samples were draw at pre-induction, 4 h and 24 h post-induction respectively. Serum level of cardiac troponin I, creatine kinase MB and myoglobin were analyzed. RESULTS: There were no significant changes of troponin I, creatine kinase MB and myoglobin in Group S between pre-induction and 4 h or 24 h post-induction (P > 0.05). And there was also no significant differences as compared with Group PR (P > 0.05). CONCLUSION: At the concentration range of 1.6%-3%, long-term sevoflurane anesthesia does not cause detectable changes of markers of myocardial damage or toxicity.

[Relationship between adiponectin and beta-cell function in abdominal visceral obesity women].

OBJECTIVE: To investigate the relationship between adiponectin and beta-cell function in abdominal visceral obesity women. METHODS: Nine abdominal visceral obesity women (VO), 9 normal subjects (C) and 7 patients with type 2 diabetes mellitus (T2DM) were enrolled in the study. Beta-cell function and insulin sensitivity were determined by hyperglycemic clamp, fasting serum adiponectin was assayed by ELISA and regional body fat was measured by MRI. RESULT: The levels of first phase insulin release (FPIR), glucose disposal rates (GDR), insulin sensitivity index (ISI) and adiponectin were significantly elevated in control group compared with VO group and T2DM group. As compared with T2DM group, the levels of adiponectin, FPIR, second phase insulin release (SPIR) and maximum insulin release (INS(max)) increased significantly in VO group. Multiple stepwise regression analysis showed that age, FPIR and GDR were positively correlated to adiponectin (B=0.145, 0.194, 0.277 respectively, all P<0.05), while waist-hip ratio was negatively correlated with adiponectin (B=-7.424, P<0.05). CONCLUSION: The visceral obesity women have lower adiponectin levels, and hyperadiponectinemia may be the link with insulin secretion.

Determination of theophylline concentration in serum by chemiluminescent immunoassay.

OBJECTIVE: This study aimed to establish chemiluminescent immunoassay (CLIA) for quantitative determination of theophylline levels in human serum. METHODS: To measure the concentration of theophylline (n=122) and evaluate the assay. RESULTS: The linear range of the CLIA method was 0.51-40 mg/L (Y=1.02X+0.44, r=0.995). The intra and inter CV (coefficient variance) of CLIA were 3.20% and 3.57%, respectively. The average recovery rate was 102.3%. This method was free from interference by brilirubin (<200 micromol/L), hemoglobin (<10 g/L), and triglycerides (<15 mmol/L). CONCLUSION: This method is simple, convenient and precise for clinical pharmacokinetics study of theophylline.