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ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang （HYT） on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group， a model group， a euthyrox group （20 μg·kg-1）， a HYT group （12.06 g·kg-1）， a HYT without Sargassum （HYT-H） group （9.90 g·kg-1）， a HYT without Glycyrrhizae Radix et Rhizoma （HYT-G） group （10.26 g·kg-1）， a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma （HYT-HG） group （8.10 g·kg-1）， and a Sargassum and Glycyrrhizae Radix et Rhizoma （HG） group （3.96 g·kg-1）. The blank group was given deionized water by gavage， and the others were given propylthiouracil （PTU） to replicate the goiter pathological model. Euthyrox was taken as a positive control drug， and the rest of the Chinese medicine groups were given the corresponding decoction by gavage， the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and the contents of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， reactive oxygen species （ROS） in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 （Keap1）， nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group， the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues （P<0.05， P<0.01）， significantly reduced activities of SOD and GSH-Px in the liver （P<0.01）， significantly increased mRNA expression of Keap1 （P<0.01）， and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. Compared with the model group， the HYT group manifested significantly reduced serum levels of AST， ALT， and ALP （P<0.05， P<0.01）， significantly reduced contents of MDA and ROS in liver tissue （P<0.01）， significantly increased the activities of SOD and GSH-Px （P<0.01）， significantly decreased mRNA expressions of Keap1， p53， and Caspase-3 （P<0.01）， and significantly increased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020， Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats， and the effect is better than that of the HG group， the euthyrox group， and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.
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Objective:To investigate the clinicopathological features, treatment and prognosis of neuroendocrine carcinoma of the breast.Methods:Clinical data of 26 patients with neuroendocrine carcinoma of the breast admitted to the Northern Jiangsu People's Hospital from July 2013 to Mar 2021 were analyzed.Results:All 26 cases were female, the average aged of (62.81±11.95) years, the first clinical manifestations were painless breast masses, the average size being of (23.34±9.47) mm. At the time of diagnosis, regional lymph node metastasis was found in 4 cases, 1 case developed distant metastasis. Most patients' were on stage Ⅱ by TNM staging, molecular typing was Luminal A, and invasive mammary carcinoma with neuroendocrine differentiation was most common, with positive rates of ER and PR of 96%, the positive rate of CgA and Syn were 69% and 100%, and there was not positive expression of HER2. All patients received surgical treatment, 25 patients underwent postoperative adjuvant therapy. Twenty-five patients were followed up for a median follow-up time of 39.50 months. During the follow-up, 3 cases developed distant metastasis, 1 case died, the mean survival time was (40.81±26.90) months, there was ao satistically significant difference compared with invasive mammary carcinoma ( t=1.291, P=0.209). The mean disease free interval is (39.96±27.58) months. The overall survival and disease free survival at 1, 2 and 5 years are 100%, 100% and 87%, respectively. Conclusions:Neuroendocrine carcinoma of the breast occurs more frequently in elderly women, often with large tumor size, low rate of regional lymph node and distant metastasis, moderate histological grade, early clinical stage, and the molecular typing is mostly Luminal A.The overall prognosis is fair.
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Invasion and metastasis are the leading causes of death from breast cancer. Epithelial-mesenchymal transition (EMT) can induce cancer metastasis by promoting tumor malignances and reprogramming tumor metabolism. As an important part of glucose metabolism, aerobic glycolysis not only provides sufficient energy for rapid growth of tumor cells, but also provides metastasis advantage for tumor cells by promoting the EMT process. In addition, the crosstalk network between glycolysis and EMT synergistically triggers cancer metastasis. Therefore, abnormal glucose metabolism and EMT play a key role in the occurrence and development of breast cancer metastasis, suggesting its clinical promise for the management of breast cancer metastasis.