Pharmacological Mechanism of Wumeiwan in Treating Lung Metastasis of Breast Cancer / 中国实验方剂学杂志

Objective:To explore the potential target and mechanism of Wumeiwan in the treatment of lung metastasis of breast cancer by network pharmacological analysis and experimental verification. Method:The databases of active ingredients and targets of Wumeiwan were established through Traditional Chinese Medicine Systems Pharmacology（TCMSP） Database and Analysis Platform，and the targets of lung metastasis of breast cancer were established through the GeneCards database and Online Mendelian Inheritance in Man（OMIM） database，and the data of Chinese medicine targets and disease targets were matched. Cytoscape 3.6.0 software was used to establish the network analysis of traditional Chinese medicine-active ingredients-therapeutic targets，and the interaction relationship between key target proteins was analyzed by STRING database. Target gene ontology（GO） analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） signal pathway enrichment analysis were performed by using the Biological Information Annotation Database. Result:A total of 108 possible important targets for Wumeiwan in the treatment of lung metastasis of breast cancer were found，including interleukin 6（IL6），cysteine aspartate-specific protease-3（CASP3），vascular endothelial growth factor A（VEGFA），epidermal growth factor receptor（EGFR），mitogen-activated protein kinase（MAPK8）， and others. GO enrichment analysis yielded 29 cell components（CC），1 218 biological processes（BP） and 125 molecular functions（MF） related to lung metastasis of breast cancer，and KEGG enrichment analysis yielded 118 pathways related to lung metastasis of breast cancer（<italic>P<</italic>0.05），including MAPK signaling pathway and apoptosis pathway. <italic>In vitro</italic> experiments showed that cinnamaldehyde， the active ingredient of Wumeiwan， could induce apoptosis，inhibit proliferation and migration of MCF7 cells，partially validating the predicted results of network pharmacology to a certain extent. Conclusion:The therapeutic effect of Wumeiwan on lung metastasis of breast cancer may be multi-target，multi-pathway and multi-mechanism. The results of this study provide more evidence for the clinical application of Wumeiwan.

Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice / 中国中药杂志

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Brucine inhibits bone metastasis of breast cancer cells by suppressing Jagged1/Notch1 signaling pathways / 中国结合医学杂志

<p><b>OBJECTIVE</b>To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis.</p><p><b>METHODS</b>The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 μmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-β1 (TGF-β1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-β1, NF-κB and Hes1 (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.</p>

Clinical observation on treatment of hyperplasia of mammary gland by Lirukang Granule / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and mechanism of Lirukang Granule in treating hyperplasia of mammary gland (HMG).</p><p><b>METHODS</b>One hundred patients with HMG were randomly assigned to two groups, 50 in each group. The patients in the treated group were orally administered with LRKG thrice a day, one package each time, and those in the control group were given orally Rukuaixiao Tablet thrice a day, 4 tablets each time. The therapeutic course for both groups was 4 months. The clinical efficacy, pain alleviating rate, as well as changes of local sign and symptom scores were observed before and after treatment. The changes of serum estradiol (E(2)), progesterone (P), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) in some randomly selected patients (24 patients in the treated group and 24 in the control group) before and after treatment were measured with radioimmunoassay.</p><p><b>RESULTS</b>The total clinical efficacy in the treated group was superior to that in the control group, significant difference was shown between the two groups (P < 0.01). The cure-effective rate and total effective rate in the treated group were 70.0% and 88.0% respectively, significantly higher than those in the control group (38.0% and 64.0%) respectively (P < 0.01), and the pain alleviating rate in the treated group was also significantly higher in the former than that in the latter (88.0% vs 64.0%, P < 0.05). Moreover, the treated group showed obvious superiority in improving the patients' symptom and sign scores (P < 0.01), and abnormalities of gonadal hormone as compared with the respective items in the control group (P < 0.01).</p><p><b>CONCLUSION</b>LRKG has good efficacy in the treatment of HMG, and its mechanism may be related to the regulation on endocrine and immune function.</p>