Background: Increasing data suggest that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes, but there are limited data on the association of these conditions in early pregnancy with subsequent miscarriage. Methods: In this prospective cohort study, we screened 3315 women at low risk for thyroid dysfunction at four to eight weeks' gestation from iodine-sufficient areas of China between January 2012 and September 2012. Thyrotropin (TSH), free thyroxine (fT4), and the autoantibodies thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured. Based on these results, women were divided into four groups for comparison: euthyroidism (ET), isolated SCH, isolated TAI (positive TPOAb or/and TgAb), and SCH with TAI (SCH+TAI). The SCH group was stratified into two subgroups (SCH 1 and SCH 2) on the basis of the level of TSH (2.5≤TSH<5.22 or 5.22≤TSH<10 respectively). Accordingly, the SCH+TAI group was also stratified into two subgroups (SCH+TAI 1 and SCH+TAI 2). The outcome of interest was miscarriage, defined as spontaneous pregnancy loss prior to 20 weeks. Results: Compared to women with ET, the risk of miscarriage was significantly higher among women with SCH 2 (7.1% vs. 2.2%, aOR 3.40 [CI 1.62–7.15]; p=0.002), isolated TAI (5.7% vs. 2.2%, aOR 2.71 [CI 1.43–5.12]; p=0.003), SCH+TAI 1 (10.0% vs. 2.2%, aOR 4.96 [CI 2.76–8.90]; p=0.000), and SCH+TAI 2 (15.2% vs. 2.2%, aOR 9.56 [CI 3.76–24.28]; p=0.000). The gestational ages of 110 women at miscarriage were lower among women with subclinical thyroid abnormalities compared to ET (11.13±3.21 weeks with subclinical thyroid abnormalities vs. 9.33±1.71 weeks with ET; p=0.024). In parallel with the higher TSH levels, there were earlier gestation ages at miscarriage between subgroups of SCH and SCH+TAI (SCH 1 vs. SCH 2: 10.79±1.77 vs. 9.70±1.47 weeks, p=0.039; SCH+TAI 1 vs. SCH+TAI 2: 9.59±1.97 vs. 8.88±1.24 weeks, p=0.031). Conclusions: Women with SCH and TAI are at an increased risk of miscarriage between four and eight gestational weeks. Women with a combination of SCH and TAI were found to have the highest risk and earlier gestational ages of miscarriage.

Background: Inflammasomes, which mediate maturation of interleukin-1β (IL-β) and interleukin-18 (IL-18) and lead to pyroptosis, have been linked to various autoimmune disorders. This study investigated whether they are involved in the pathogenesis of autoimmune thyroiditis (AIT). Methods: We collected thyroid tissues from 50 patients with AIT and 50 sex- and age-matched controls. Serum levels of free T3, free T4, thyrotropin, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured by electrochemiluminescent immunoassays. Expression of several inflammasome components, the NOD-like receptor (NLR) family pyrin domain containing 1 (NLRP1), NLRP3, CARD-domain containing 4 (NLRC4), absent in melanoma 2 (AIM2), the apoptosis-associated speck-like protein that contains a caspase recruitment domain (ASC), caspase-1, IL-1β, and IL-18 was determined by real-time PCR and western blot. Immunohistochemistry was used to localize the expression of NLRP1, NLRP3, NLRC4, and AIM2. The Nthy-ori 3-1 thyroid cell line was stimulated with tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-17A, interleukin-6, and poly(dA:dT). The levels of IL-18 and IL-1β in the cell supernatant were measured by enzyme-linked immunosorbent assay, and lactate dehydrogenase was quantified by absorptiometry. ASC specks were examined by confocal immunofluorescence microscopic analysis. Cell death was examined by flow cytometry, and the N-terminal domain of gasdermin D was detected by western blot analysis. Results: Expression of NLRP1, NLRP3, NLRC4, AIM2, ASC, caspase-1, pro IL-1β, pro IL-18, mRNA, and protein was significantly increased in thyroid tissues from patients with AIT, and enhanced posttranslational maturation of caspase-1, IL-18 and IL-1β was also observed. Expression of NLRP1, NLRP3, NLRC4, and AIM2 was localized mainly in thyroid follicular cells adjacent to areas of lymphatic infiltration. The thyroid mRNA level of NLRP1 and ASC was correlated to the serum TPOAb and TgAb levels in the AIT group. TNF-α and IFN-γ had a priming effect on the expression of multiple inflammasome components in thyroid cells. IFN-γ was found to strengthen poly(dA:dT)-induced cell pyroptosis and bioactive IL-18 release. Conclusion: Our work has demonstrated for the first time that multiple inflammasomes are associated with AIT pathogenesis. The identified NLRP3, NLRP1, NLRC4, AIM2 inflammasomes and their downstream cytokines may represent potential therapeutic targets and biomarkers of AIT.

Background: Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID.Methods: We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD.Results: The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto’s thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves’ disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls.Conclusions: This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels.Systematic Review Registration: PROSPERO, identifier CRD42021251557.

Objectives Our study aimed to distinguish the ability of anthropometric indices to assess the risk of metabolic syndrome (MetS). Design Prospective cohort study. Setting Shenyang, China. Participants A total of 379 residents aged between 40 and 65 were enrolled. 253 of them were free of MetS and had been followed up for 4.5 years. Methods At baseline, all the participants underwent a thorough medical examination. A variety of anthropometric parameters were measured and calculated, including waist circumference (WC), body mass index (BMI), a body shape index (ABSI), abdominal volume index (AVI), body adiposity index, body roundness index, conicity index, waist-to-hip ratio and visceral adiposity index (VAI). After 4.5 year follow-up, we re-examined whether participants were suffering from MetS. A receiver operating characteristic (ROC) curve was applied to examine the potential of the above indices to identify the status and risk of MetS. Outcomes Occurrence of MetS. Results At baseline, 33.2% participants suffered from MetS. All of the anthropometric indices showed clinical significance, and VAI was superior to the other indices as it was found to have the largest area under the ROC curve. After a 4.5 year follow-up, 37.8% of men and 23.9% of women developed MetS. ROC curve analysis suggested that baseline BMI was the strongest predictor of MetS for men (0.77 (0.68–0.85)), and AVI was the strongest for women (0.72 (0.64–0.79)). However, no significant difference was observed between WC and both indices. In contrast, the baseline ABSI did not predict MetS in both genders. Conclusions The present study indicated that these different indices derived from anthropometric parameters have different discriminatory abilities for MetS. Although WC did not have the largest area under the ROC curve for diagnosing and predicting MetS, it may remain a better index of MetS status and risk because of its simplicity and wide use.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China. This was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011. A total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM. Less than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.