RESUMO
Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP). Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein-protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells. Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug-compound-hub target gene-pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells. Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research.
RESUMO
BACKGROUND: Total thyroidectomy is no doubt the standard procedure for patients with bilateral thyroid carcinoma in pediatrics. However, for lesions confined in unilateral thyroid gland, lobectomy or radical total thyroidectomy is still controversial in pediatrics. METHODS: Thirty-five cases of pediatric thyroid carcinoma which were confirmed by pathology were retrospectively analyzed in our hospital from 2005 to 2016. In 13 cases of unilateral lesions, 6 received lobectomy, while others underwent total thyroidectomy. Recurrence and complications were compared between 2 groups. Also, there were 20 cases of primary total thyroidectomy and 4 cases of supplementary resection of the residual gland. The short-term complications were compared. RESULTS: There were no differences between groups of lobectomy and total thyroidectomy in size, extrathyroid extension, stage, cervical lymph nodes metastases, and distant metastases. They were the same in incidence of postoperative hypocalcemia, calcium supplement, recurrent laryngeal nerve damage, and recurrence rate and mortality, except that the length of stay in hospital was shorter in lobectomy group. Patients in supplementary resection were more likely to present the symptoms of postoperative hypocalcemia and hypokalemia, and it was difficult to identify the parathyroid gland during the operation by comparing with patients of primary total thyroidectomy. CONCLUSIONS: Thyroid carcinoma in pediatrics is inclined to be multifocal, and even in a single focus, the volume is large. Total thyroidectomy does not bring more complications. In contrast, the morbidity increases in staged resection. Endocrine hormone supplement can satisfy the need for growth and development. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.