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Ling Shan Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China
Department of Endocrinology and Metabolism, People's Hospital of Liaoning Province, Shenyang, People’s Republic of China

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Yingying Zhou Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Shiqiao Peng Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Xinyi Wang Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China
Department of Laboratory Medical, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Zhongyan Shan Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Weiping Teng Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Background

Pregnant women with subclinical hypothyroidism are associated with an increased risk of spontaneous abortion. This study aims to investigate the mechanisms underlying the effects of maternal subclinical hypothyroidism during early pregnancy on abortion in the uterus, focusing upon the LIF/STAT3 signaling pathway.

Methods

One hundred five Wistar rats were randomly divided into three groups (35 rats in each group): control (CON) group, subclinical hypothyroidism (SCH) group and overt hypothyroidism (OH) group. We examined the weight of rat uteri, rat placenta and embryos. We also determined the number of implantation sites and the embryo absorption rates. The protein and mRNA expressions of TSHR, TR-α, TR-β, LIFR, gp130, JAK1, p-STAT3 and STAT3 were measured by immunohistochemical staining, real-time PCR and Western blotting.

Results

The weights of rat uteri, rat placenta and embryos were significantly reduced in the SCH and OH groups. The number of implantation sites was significantly decreased in the SCH and OH groups, while embryo absorption rates were significantly increased. The mRNA and protein expressions of TSHR were upregulated in the SCH and OH groups, while TR-α and TR-β showed no difference when compared between the three groups. The expression levels of LIFR, gp130, JAK1 and p-STAT3 were significantly higher in the SCH and OH groups.

Conclusions

Clinical and subclinical hypothyroidism during early pregnancy might cause adverse pregnancy outcomes. Implantation failure in rats with subclinical hypothyroidism was associated with abnormal LIF/STAT3 signaling.

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Shan Wu College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, People’s Republic of China
Research Center for Translational Medicine, Cancer Stem Cell Institute, East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

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Jianjun Zhou Research Center for Translational Medicine, Cancer Stem Cell Institute, East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

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Jing Guo Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, People’s Republic of China

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Zhan Hua Department of General Surgery, China-Japan Friendship Hospital, Beijing, People’s Republic of China

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Jianchen Li College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, People’s Republic of China

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Zai Wang Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, People’s Republic of China

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Angiogenesis has a pivotal role in the growth and metastasis of pancreatic neuroendocrine tumors (PNETs). Apatinib inhibits angiogenesis as a highly selective KDR inhibitor and has been used to treat advanced gastric cancer and malignancies in clinical settings. However, the efficacy of apatinib in PNETs remains unclear. The aim of this study was to compare the antitumor efficacy of apatinib with that of the standard PNET drug sunitinib in our subcutaneous and liver metastasis models of insulinoma and non-functional PNET. Our results revealed that apatinib had a generally comparable or even superior antitumor effect to that of sunitinib on primary PNET, and it inhibited angiogenesis without directly causing tumor cell cytotoxicity. Apatinib inhibited the tumor in a dose-dependent manner, and the high dose was well tolerated in mice. We also found that the apatinib efficacy in liver metastasis models was cell-type (disease) selective. Although apatinib efficiently inhibited INR1G9-represented non-functional PNET liver metastasis, it led to the emergence of a hypoxic area in the INS-1-represented insulinoma and promoted liver metastasis. Our study demonstrated that apatinib has promise for clinical applications in certain malignant PNETs, and the application of anti-angiogenesis drugs to benign insulinomas may require careful consideration.

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Mengxue Yang Department of Endocrinology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, China
Department of Endocrinology, Zunyi Medical University, Zunyi, China

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Bowen Sun Department of Endocrinology, Zunyi Medical University, Zunyi, China

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Jianhui Li Department of Endocrinology, Ningbo No. 2 Hospital, Ningbo, China

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Bo Yang Department of Endocrinology, Zunyi Medical University, Zunyi, China

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Jie Xu School of Public Health, Zunyi Medical University, Zunyi, China

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Xue Zhou Department of Endocrinology, Zunyi Medical University, Zunyi, China

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Jie Yu School of Public Health, Zunyi Medical University, Zunyi, China

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Xuan Zhang Department of Endocrinology, Zunyi Medical University, Zunyi, China

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Qun Zhang Department of Endocrinology, Ningbo No. 2 Hospital, Ningbo, China

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Shan Zhou Department of Endocrinology, Ningbo No. 2 Hospital, Ningbo, China

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Xiaohua Sun Department of Endocrinology, Ningbo No. 2 Hospital, Ningbo, China

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Objectives

The pathogenesis of Graves’ disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China.

Design and methods

Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis and partial least squares-discriminant analysis (PLS-DA).

Results

The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P < 0.05).

Conclusions

The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.

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