Network Pharmacology-based Study of Bushen Zhuyun Prescription in Treatment of Recurrent Spontaneous Abortion / 中国实验方剂学杂志

Objective:To explore the active components， targets， and signaling pathways responsible for Bushen Zhuyun prescription in treating the recurrent spontaneous abortion （RSA） based on network pharmacology and uncover its potential mechanism by molecular docking and in vitro cell experiments. Method:The active components of Bushen Zhuyun prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） and the published articles， followed by the prediction of drug action targets based on such platforms as DrugBank and SwissTargetPrediction. GeneCards and Online Mendelian Inheritance in Man （OMIM） were searched to obtain the RSA targets， which were then intersected with the targets of Bushen Zhuyun Decoction. Following the plotting of Bushen Zhuyun prescription-compound-target-RSA network by Cytoscape 3.7.1， the protein-protein interaction （PPI） network was then constructed with STRING for screening the core network. The resulting common targets were then subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using R software. Autodock Vina 1.1.2 was used for molecular docking. The activation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/AKT） signaling pathway by Bushen Zhuyun prescription was verified in human umbilical vein endothelial cells （HUVEC） <italic>in vitro</italic>. Result:It was found that 49 potential active components of Bushen Zhuyun prescription might act on 133 RSA targets. GO enrichment analysis yielded 470 biological processes， with angiogenesis， vascular development， cellular proliferation， and oxidative activity mainly involved. KEGG enrichment analysis revealed 103 signaling pathways （<italic>P</italic><0.05）， and the PI3K/AKT signaling pathway， advanced glycation end product （AGE）/receptor for advanced glycation end product （RAGE） signaling pathway， and tumor necrosis factor （TNF） signaling pathway were the main ones. As indicated by molecular docking， the Vina scores of the main active component kaempferol with AKT1 and vascular endothelial growth factor A （VEGFA） were the lowest and similar. It was confirmed <italic>in vitro</italic> cell experiments that Bushen Zhuyun prescription activated the PI3K/AKT signaling pathway and up-regulated the expression of VEGFA and downstream AKT protein to promote angiogenesis. Conclusion:Bushen Zhuyun prescription promotes angiogenesis at the maternal-fetal interface by regulating angiogenesis and cellular proliferation， activating the PI3K/AKT pathway， and up-regulated the VEGFA expression， which is beneficial to the formation of placenta in early pregnancy and the maintenance of early pregnancy. This study has provided ideas for new drug development.

Intervention of Modified Yupingfeng San Combined with Aspirin on D-dimer， PagT Levels of RSA with Seronegative APS / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of aspirin combined with modified Yupingfeng San on patients with recurrent spontaneous abortion and Seronegative antiphospholipid syndrome. Method:From December 2016 to March 2018, 109 cases of recurrent spontaneous abortion patients with seronegative antiphospholipid syndrome in Affiliated Hospital of Nanjing University of Chinese Medicine were selected as the study objects. According to the random number table, they were divided into three groups:blank group, control group and study group. The blank group was treated with folic acid tablets, 1 pill/time, qd, as placebo, the control group was treated with folic acid tablets, 1 pill/time, qd, Danshen pills, 4 pills/time, tid, and aspirin, 1 pill/time, tid, and the study group was treated with folic acid tablets, 1 pill/time, qd, aspirin, 1 pill/time, tid, and modified Yupingfeng San, 150 mL/time, bid. These patients were all asked for pregnancy preparation for 1 year and treated with aspirin, 1 pill/time, tid, and progesterone pills, 1 pill/time, tid, since the beginning of pregnancy until 13 weeks or abortion. The pregnancy rate, miscarriage rate, coagulation index before and after treatment, traditional Chinese medicine (TCM) symptom score as well as months of abortion were all observed and compared. Result:The coagulation index and TCM symptom score of the study group were significantly lower than those before treatment (PPPPPConclusion:The data proved that the combination of anti-coagulation medicine with either single herb or herbal compound can improve the curative effect of the patients, and traditional Chinese herbal compound can regulate the immune system, reduce the thrombosis and improve the symptoms of TCM, which made the curative efficacy more prominent. However, more samples were needed for further research. Because the time of fetal protection may not change the outcome of pregnancy, the therapy should be maintained at least until the end of the early pregnancy.

Women with recurrent spontaneous abortion have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.

Professor LU Qibin's Clinical Experience in the Diagnosis and Treatment of Recurrent Spontaneous Abortion / 浙江中医药大学学报

[Objective]In this paper, valuable experience would be shared and the culture of Chinese medicine will be inherited through introducing the clinical experience of Professor LU Qibin in the diagnosis and treatment of RSA. [Methods]From the point of cause and pathology as well as therapeutic method of the disease, the author discussed the special treatment of Professor LU Qibin. At the same time, the author focuses on introducing the dialectics and characteristics of professor LU Qibin's treatment of complicated recurrent spontaneous abortion. In order to elaborate clearly, some clinical cases were reported. [Results]Professor LU Qibin has summarized that spleen-kidney deficiency is the foundation of recurrent spontaneous abortion. In consequence, invigorating the spleen and kidney is the basic treatment. For the complicated recurrent spontaneous abortion, Professor LU Qibin has many assistant methods on the basis of invigorating spleen and kidney. Such as clearing heat and activating blood, warming and invigorating the spleen and kidney and so on. Furthermore, Professor LU Qibin insists the treatment of traditional Chinese medicine coordinate with western medical therapies. In the reported cases, patients were successfully cured. [Conclusion]Professor LU Qibin is experienced and the clinical curative effect is remarkable. Hence, the clinical experience of Professor LU Qibin in the diagnosis and treatment of recurrent spontaneous abortion was worth of learning and wide application.

Study on association of HLA-E with recurrent spontaneous abortion / 中国免疫学杂志

Objective:To explore the mechanism of association between recurrent spontaneous abortion(RSA) and the polymorphism of HLA E,had detected the frequencies of five HLA E alleles in 53 women with RSA and 156 random Shanghai Chinese controls.Methods:PCR sequence specific oligonucleotide (PCR SSO) typing was carried to detect polymorphism in exon2 and exon3 of HLA E gene.Results:HLA E *0101 is the most common allele in both RSA patients and controls(50% and 43.09% respectively).HLA E *01031 and E *01032 were detected with allele freqencies of 23.79% and 33.12% in controls,20.75% and 29.25% in RSA.No HLA E *0102 and E *0104 alleles could be detected in both groups.Conclusion:Maternal HLA E polymorphism does not associated with pathogenesis of RSA.