BackgroundPrevious studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly.MethodsIn this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite.ResultsSCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L.ConclusionStrictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.
Background: Cuproptosis-related long non-coding RNA (lncRNA) disease is associated with the development and progression of tumors. We aimed to investigate the prediction of cuproptosis-related lncRNA on the prognosis and immunotherapy of patients with thyroid carcinoma (THCA). Methods: The thyroid cancer-associated expression data and lnc RNAs data were downloaded from The Cancer Genome Atlas (TCGA) and Ensembl database. The prognostic model of cuproptosis-related lncRNAs was successfully constructed through Lasso regression analysis and Cox regression analysis. Then, the prognostic value of prognostic model of cuproptosis-related lncRNAs was tested through the survival analysis, ROC curves and nomographic charts. Finally, the prognostic model of cuproptosis-related lncRNAs associated with immunity and mutational load of tumors was analyzed, and potential targeted drugs for THCA were predicted. Results: A cuproptosis-related lncRNA model of THCA (AC026100.1, AF235103.3, LNCSRLR) was successfully constructed, which has an independent prognostic value. Moreover, the cuproptosis-related lncRNA model was associated with immune signatures and mutational load in most tumors, showing its high correlation with the sensitivity of targeted drugs such as 5-Fluorouracil, Bleomycin, Rapamycin and Sunitinib. Conclusion: The cuproptosis-related lncRNA model of THCA has promising applications in the treatment and prognosis of THCA.
BackgroundPrevious evidence suggests that perfluoroalkyl and polyfluoroalkyl substances (PFASs) adversely affect ovarian function and female fecundity. However, the evidence remains insufficient to infer a direct relationship between PFAS exposure and adverse assisted reproductive technology (ART) outcomes. To fill this gap, we examined follicular fluid PFAS exposure and ART outcomes in patients with poor ovarian reserve (POR) in a prospective study.MethodsIn total, 147 women with POR were included. Eight PFASs were measured in follicular fluid (n=104) samples using simultaneous analysis by ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. The PFAS contamination status of the patients’ follicular fluid and the association between characteristics and ART outcomes were investigated by logistic regression.ResultsAfter adjustment for age and BMI, PFOA, PFNA, PFHxS and ∑PFAS were strongly associated with a decreased probability of pregnancy (PFOA highest vs. lowest tertile: OR=1.95, 95% CI: 1.61, 2.38; PFNA highest vs. lowest tertile: OR= 3.0, 95% CI: 2.46, 3.68; PFHxS highest vs. lowest tertile: OR= 1.95, 95% CI: 1.61, 2.35; ∑PFAS second vs. lowest tertile: OR=3.31, 95% CI: 2.74, 3.89). PFOS and PFUnDA were inversely associated with failed implantation. No relationships were noted between failed implantation and other PFAS analytes. The same result was obtained when using live birth as an outcome measure.ConclusionsIn women with POR, follicular fluid PFAS exposure may decrease the probability of clinical pregnancy and live birth.
Purpose The pathogenesis of Graves’ orbitopathy/thyroid-associated orbitopathy (TAO) is still unclear, and abnormal DNA methylation in TAO has been reported. Thus, selecting and exploring TAO biomarkers associated with DNA methylation may provide a reference for new therapeutic targets. Methods The TAO-associated expression data and methylation data were downloaded from The Gene Expression Omnibus database. Firstly, weighted gene co-expression network analysis was used to obtain the TAO-related genes, which were intersected with differentially methylated genes (DMGs), and differentially expressed genes between TAO samples and normal samples to obtain TAO-associated DMGs (TA-DMGs). Thereafter, the functions of the TA-DMGs were analyzed, and diagnostic markers were screened by least absolute shrinkage and selection operator (Lasso) regression analysis and support vector machine (SVM) analysis. The expression levels and diagnostic values of the diagnostic markers were also analyzed. Furthermore, single gene pathway enrichment analysis was performed for each diagnostic marker separately using gene set enrichment analysis (GSEA) software. Next, we also performed immune infiltration analysis for each sample in the GSE58331 dataset using the single-sample GSEA algorithm, and the correlation between diagnostic markers and differential immune cells was explored. Lastly, the expressions of diagnostic markers were explored by quantitative real-time polymerase chain reaction (qRT-PCR). Results A total of 125 TA-DMGs were obtained. The enrichment analysis results indicated that these TA-DMGs were mainly involved in immune-related pathways, such as Th1 and Th2 cell differentiation and the regulation of innate immune response. Moreover, two diagnostic markers, including S100A11 and NKD2, were obtained by Lasso regression analysis and SVM analysis. Single gene pathway enrichment analysis showed that S100A11 was involved in protein polyufmylation, pancreatic-mediated proteolysis, and NKD2 was involved in innate immune response in mucosa, Wnt signaling pathway, etc. Meanwhile, immune cell infiltration analysis screened 12 immune cells, including CD56 dim natural killer cells and Neutrophil cells that significantly differed between TAO and normal samples, with the strongest positive correlation between NKD2 and CD56 dim natural killer cells. Finally, the qRT-PCR illustrated the expressions of NKD2 and S100A11 between normal and TAO. Conclusion NKD2 and S100A11 were screened as biomarkers of TAO and might be regulated by DNA methylation in TAO, providing a new reference for the diagnosis and treatment of TAO patients.
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