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      The exploration of Hashimoto's Thyroiditis related miscarriage for better treatment modalities

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          Abstract

          Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disease (ATD) worldwide and is strongly associated with miscarriage and even recurrent miscarriage (RM). Moreover, with a deepening understanding, emerging evidence has shown that immune dysfunctions caused by HT conditions, including imbalanced subsets of CD4+ T-helper cells, B regulatory (Breg) cells, high expression levels of CD56dim natural killer (NK) cells, and cytokines, possibly play an important role in impairing maternal tolerance to the fetus. In recent years, unprecedented progress has been made in recognizing the specific changes in immune cells and molecules in patients with HT, which will be helpful in exploring the mechanism of HT-related miscarriage. Based on these findings, research investigating some potentially more effective treatments, such as selenium (Se), vitamin D3, and intravenous immunoglobulin (IVIG), has been well developed over the past few years. In this review, we highlight some of the latest advances in the possible immunological pathogenesis of HT-related miscarriage and focus on the efficacies of treatments that have been widely introduced to clinical trials or practice described in the most recent literature.

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          Mechanisms Controlling PD-L1 Expression in Cancer

          The engagement of programmed cell death protein 1 (PD-1; encoded by the PDCD1 gene) receptor expressed on activated T cells and its ligand programmed death-ligand 1 (PD-L1; encoded by the CD274 gene) is a major co-inhibitory checkpoint signaling that controls T-cell activities. Various types of cancers express high levels of PD-L1 and exploit the PD-L1/PD-1 signaling to evade T-cell immunity. Blocking the PD-L1/PD-1 pathway has consistently shown remarkable anti-tumor effects in patients with advanced cancers and is recognized as the gold standard for developing new immune checkpoint blockade (ICB) and combination therapies. However, the response rates of anti-PD-L1 have been limited in several solid tumors. Therefore, furthering our understanding of the regulatory mechanisms of PD-L1 can bring substantial benefits to patients with cancers by improving the efficacy of current PD-L1/PD-1 blockade or other ICBs. In this review article, we provide current knowledge of PD-L1 regulatory mechanisms at the transcriptional, posttranscriptional, post-translational, and extracellular level, and discuss the implications of these findings in cancer diagnosis and immunotherapy. Immune checkpoint programmed death-ligand 1 (PD-L1) plays a critical role in facilitating tumor immune evasion. Cha et al. discuss the mechanisms regulating PD-L1 expression and explore how targeting those mechanisms may lead to potential therapeutic strategies and biomarkers to improve response rates to immunotherapy.
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            Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline.

            The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.
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              Hashimoto thyroiditis: clinical and diagnostic criteria.

              Hashimoto thyroiditis (HT), now considered the most common autoimmune disease, was described over a century ago as a pronounced lymphoid goiter affecting predominantly women. In addition to this classic form, several other clinico-pathologic entities are now included under the term HT: fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, and painless thyroiditis (sporadic or post-partum). All forms are characterized pathologically by the infiltration of hematopoietic mononuclear cells, mainly lymphocytes, in the interstitium among the thyroid follicles, although specific features can be recognized in each variant. Thyroid cells undergo atrophy or transform into a bolder type of follicular cell rich in mitochondria called Hürthle cell. Most HT forms ultimately evolve into hypothyroidism, although at presentation patients can be euthyroid or even hyperthyroid. The diagnosis of HT relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features. The treatment remains symptomatic and based on the administration of synthetic thyroid hormones to correct the hypothyroidism as needed. Surgery is performed when the goiter is large enough to cause significant compression of the surrounding cervical structures, or when some areas of the thyroid gland mimic the features of a nodule whose cytology cannot be ascertained as benign. HT remains a complex and ever expanding disease of unknown pathogenesis that awaits prevention or novel forms of treatment.
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                Author and article information

                Journal
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2020
                29 August 2020
                : 17
                : 16
                : 2402-2415
                Affiliations
                Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.74, Linjiang Rd, Yuzhong Dist, Chongqing 404100, China.
                Author notes
                ✉ Corresponding author: Prof. Guobing Yin, Ph.D., Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.74, Linjiang Rd, Yuzhong Dist, Chongqing, 404100, People's Republic of China. Tel.: 86+15823267119; E-mail: yinguobing@ 123456cqmu.edu.cn .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijmsv17p2402
                10.7150/ijms.48128
                7532476
                33029083
                3536f4a9-eb13-4a7d-a592-e42ee2528362
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 13 May 2020
                : 21 August 2020
                Categories
                Review

                Medicine
                hashimoto's thyroiditis,autoimmune disease,miscarriage,immune system,intravenous immunoglobulin,levothyroxine

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