BackgroundChinese herbal formulae are composed of complex components and produce comprehensive pharmacological effects. Unlike chemical drugs that have only one clear single target, the components of Chinese herbal formulae have multiple channels and targets. How to discover the pharmacological targets of Chinese herbal formulae and their underlying molecular mechanism are still under investigation.MethodsDanQi pill (DQP), which is one of the widely prescribed traditional Chinese medicines, is applied as an example drug. In this study, we used the drug target prediction model (DrugCIPHER-CS) to examine the underlying molecular mechanism of DQP, followed by experimental validation.ResultsA novel therapeutic effect pattern of DQP was identified. After determining the compounds in DQP, we used DrugCIPHER-CS to predict their potential targets. These potential targets were significantly enriched in well-known cardiovascular disease-related pathways. For example, the biological processes of neuroactive ligand–receptor interaction, calcium-signaling pathway, and aminoacyl–tRNA biosynthesis were involved. A new and significant pathway, arachidonic acid (AA) metabolism, was also identified in this study. This predicted pathway alteration was validated with an animal model of heart failure (HF). Results show that DQP had effect both on thromboxane B2 (TXB2) and Prostaglandin I2 (PGI2) in different patterns. It can down-regulate the TXB2 and up-regulate the PGI2 in diverse way. Remarkably, it also had effect on cyclooxygenase (COX)-1 and COX2 by suppressing their levels, which may be the critical and novel mechanism of cardiacprotective efficacy for DQP. Furthermore, leukotrienes B4 (LTB4) receptor, another key molecule of AA metabolism which finally mediated gastrotoxic leukotrienes, was also reduced by DQP.ConclusionsThe combination of drug target prediction and experimental validation provides new insights into the complicated mechanism of DQP.

Background The prevalence of diabetes, constituted chiefly by type 2 diabetes mellitus (T2DM), is a global public health threat. Suboptimal health status (SHS), a physical state between health and disease, might contribute to the progression or development of T2DM. Methods We conducted a prospective cohort study, based on the China Suboptimal Health Cohort Study (COACS), to understand the impact of SHS on the progress of T2DM. We examined associations between SHS and T2DM outcomes using multivariable logistic regression models and constructed predictive models for T2DM onset based on SHS. Results A total of 61 participants developed T2DM after an average of 3.1 years of follow-up. Participants with higher SHS scores had more T2DM outcomes (p = 0.036). Moreover, compared with the lowest quartile of SHS scores, participants with fourth, third, and second quartile SHS scores were found to be associated with a 1.7-fold, 1.6-fold, and 1.5-fold risk of developing T2DM, respectively. The predictive model constructed with SHS had higher discriminatory power (AUC = 0.848) than the model without SHS (AUC = 0.795). Conclusions The present study suggests that a higher SHS score is associated with a higher incidence of T2DM. SHS is a new independent risk factor for T2DM and has the capability to act as a predictive tool for T2DM onset. The evaluation of SHS combined with the analysis of modifiable risk factors for SHS allows the risk stratification of T2DM, which may consequently contribute to the prevention of T2DM development. These findings might require further validation in a longer-term follow-up study.

Objective. The exact shape of the dose-response relationship between maternal body mass index (BMI) and the risk of congenital heart defects (CHDs) in infants has not been clearly defined yet. This study aims to further clarify the relationship between maternal obesity and the risk of CHDs in infants by an overall and dose-response meta-analysis. Methods. PubMed, Embase, and Web of Science databases were searched to identify all related studies. The studies were limited to human cohort or case-control studies in English language. Random-effect models and dose-response meta-analysis were used to synthesize the results. Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias were also assessed. Results. Nineteen studies with 2,416,546 participants were included in our meta-analysis. Compared with the mothers with normal weight, the pooled relative risks (RRs) of infants with CHDs were 1.08 (95% CI=1.03-1.13) in overweight and 1.23 (95% CI=1.17-1.29) in obese mothers. According to the findings from the linear meta-analysis, we observed an increased risk of infants with CHDs (RR=1.07, 95% CI=1.06-1.08) for each 5 kg/m2 increase in maternal BMI. A nonlinear relationship between maternal BMI and risk of infants with CHDs was also found (p=0.012). Conclusion. The results from our meta-analysis indicate that increased maternal BMI is related to increased risk of CHDs in infants.

Background: One of most important concerns of postmenopausal women is obesity. The relationships between menstruation status and obesity phenotypes are unclear. This study aimed to assess the associations between menstrual status and different obesity phenotypes in women. Methods: In total, 5373 women aged ≥40 years were recruited from the Jidong and Kailuan communities. Basic information was collected via clinical examination, laboratory testing and standardized questionnaires. The women were stratified into the following three groups: menstrual period, menopausal transition period and postmenopausal period. General obesity was defined as a body mass index (BMI) of ≥28 kg/m 2. Central obesity was defined as a waist-to-hip ratio (WHR) of > 0.85. Visceral obesity was defined as the presence of nonalcoholic fatty liver disease (NAFLD) and increased pericardial fat volume (PFV). Results: The numbers of women in the menstrual, menopausal transition, and postmenopausal periods were 2807 (52.2%), 675 (12.6%) and 1891 (35.2%), respectively. The adjusted odds ratio (OR) and 95% confidence interval (CI) for central obesity among women in the menopausal transition and postmenopausal periods compared with women in the menstrual period were 0.99 (0.82-1.19) and 1.52 (1.26-1.84), respectively. The OR for NAFLD among postmenopausal women was 1.78 (1.44-2.20). The adjusted β-coefficient (standard error, SE) for PFV among postmenopausal women was 41.25 (7.49). The adjusted OR for general obesity among postmenopausal women was 1.01 (0.77-1.34). Conclusions: This study demonstrated that menopause is an independent risk factor for central and visceral obesity but not general obesity.

BackgroundThere has been little literature about leukemia epidemiology in Nanjing in recent years. We aimed to explore the incidence rate, gender and age distribution of leukemia in Nanjing using the leukemia database of the city.ResultsThe average yearly incidence rate of leukemia was 3.68/105 during 2003 - 2007 in Nanjing. There were no significant difference in gender (x2 = 3.266, p > 0.05) or seasons (x2 = 11.36, p > 0.05). The incidence rate was the highest in group aged 80~ years (18.64/105). AML accounted for approximately 36.8% of all leukemias.ConclusionsThe incidence rate of leukemia, especially in the aged population, was relatively high in Nanjing. Leukemia is the major malignant tumor in children. Therefore, more attention should be paid to leukemia in children and the aged people.