EFFECTS OF VITAMIN D RECEPTOR GENE POLYMORPHISMS ON SUSCEPTIBILITY TO TYPE 1 DIABETES MELLITUS

Objective To investigate the influence of vitamin D receptor （VDR） gene polymorphisms on susceptibility to type 1 diabetes mellitus （T1DM） in the Chinese Han population. Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamL Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects （ P = 0. 033 ） while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibihty to T1DM in the Chinese Han population of Beijing.

JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis

Objective： JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders （MPD）. The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis （PMF）. Methods： We introduced allele-specific PCR （AS-PCR） combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. Results： Fifteen PMF patients （50.0%） carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients （6.7%） harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. Conclusion： MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety:A network pharmacology and molecular docking study

BACKGROUND The therapeutic effects of a combination of Chinese medicines called Baihedihuang decoction(BD)have been clinically verified,although its molecular targets in breast cancer related anxiety remain unknown.AIM To explore the molecular mechanisms of BD for breast cancer related anxiety treatment.METHODS We used the Traditional Chinese Medicine Systems Pharmacology database to screen the active ingredients and potential targets of BD,and constructed the"drug-ingredient-target"network map with the help of Cytoscape 3.8 software.Also,we used the Online Mendelian Inheritance in Man,DrugBank,and Gencards databases to collect the disease targets of breast cancer related anxiety,and used the STRING platform to perform protein interaction analysis and construct the protein-protein interaction network.Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key targets.Molecular docking technology was used to verify the drug component/target disease network.RESULTS We screened 16 active ingredients of BD for breast cancer related anxiety,with 113 target proteins.There are 931 disease targets of breast cancer related anxiety,and finally,43 key targets and 305 Kyoto Encyclopedia of Genes and Genomes pathways were generated.The main active ingredients of BD for breast cancer related anxiety are verbascoside,β-sitosterol,stigmasterol,catalpol,etc.CDK2,TP53,HTR2A,ESR1,etc.are its key targets,and the main involved signaling pathways may include neuroactive ligand-receptor interaction pathway,5-hydroxytryptaminergic synapse,P53 signaling pathway,cGMP-PKG signaling pathway,the cAMP signaling pathway,etc.Finally,molecular docking was performed with Vina software to validate the key active ingredients in BD with the selected key action targets.The molecular docking results showed that verbascoside,β-sitosterol,stigmasterol and CDK2 could stably bind and interact through amino acid residues SER249,ARG260,PRO228,ALA282,SER276,LYS273,ASN272,etc.CONCLUSION The therapeutic effect of BD for breast cancer related anxiety is multi-level,multi-target,and multi-pathway.The findings of this study provide ideas and basis for further research.