Objective:To investigate the outcomes and influencing factors of newly diagnosed prediabetic subjects aged 40 years and above in Guiyang.Methods:A total of 10 015 residents aged 40 years and above were recruited from the Yunyan community, Guiyang, from May to August 2011. Physical examination, laboratory measurements, and questionnaires were conducted. The follow-up survey was conducted in July 2014. A total of 2 530 newly diagnosed prediabetic subjects at baseline were included in the analysis.Results:The 3-year cumulative morbidity of diabetes mellitus was 14.3%, and the risk of diabetes mellitus in combined impaired fasting glucose(IFG)and impaired glucose tolerance(IGT)groups was significantly higher than that in isolated IFG(i-IFG)or isolated IGT(i-IGT)group( P<0.01). High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes( OR=1.836, 95% CI 1.374-2.454; OR=1.398, 95% CI 1.261-1.550; OR=2.526, 95% CI 1.804-3.538, all P<0.01)and the inhibitory factors for reversion to normal glucose tolerance( OR=0.511, 95% CI 0.409-0.638; OR=0.715, 95% CI 0.661-0.774; OR=0.638, 95% CI 0.500-0.816, all P<0.01). High level of high density lipoprotein-cholesterol(HDL-C)was an promoting factor for reversion to normal glucose tolerance( OR=1.306, 95% CI 1.017-1.678, P=0.036). Subjects in the highest tertile of baseline HbA 1C level and body mass index(BMI)change before and after follow-up(ΔBMI=follow-up BMI minus baseline BMI)had a higher risk of diabetes mellitus than those in the lowest tertile( OR=2.398, 95% CI 1.733-3.322; OR=2.402, 95% CI 1.859-3.105, both P<0.01). The risk of diabetes mellitus in the significant weight loss group was reduced by 40.4% compared with the non-significant weight loss group when the subjects were divided into two groups according to the cutoff of the lower tertile of ΔBMI( RR=0.596, 95% CI 0.463-0.766, P<0.01). Conclusion:The risk of diabetes mellitus in combined IFG/IGT group was significantly higher than that in i-IFG or i-IGT group. High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes. High level of HDL-C was an promoting factor for reversion to normal glucose tolerance. Weight loss can significantly reduce the risk of progression to diabetes in individuals with prediabetes.

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg^-1·d^-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg^-1·d^-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E₂， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.