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Department of Immunology, Nanjing Medical University, Jiangsu, China
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Objective
Thyroid nodules are usually accompanied by elevated thyroglobulin (Tg) level and autoimmune thyroid diseases (AITDs). However, the relationship between Tg and AITDs is not fully understood. Dysfunction of regulatory T cells (Tregs) plays an important role in the development of AITDs. We aimed to evaluate the effects of Tg on the function of Tregs in patients with thyroid nodules.
Methods
Tg levels and the functions of Tregs in peripheral blood and thyroid tissues of patients with thyroid nodules from Nanjing First Hospital were evaluated. The effects of Tg on the function of Tregs from healthy donors were also assessed in vitro. The function of Tregs was defined as an inhibitory effect of Tregs on the effector T cell (CD4+ CD25− T cell) proliferation rate.
Results
The level of Tg in peripheral blood correlated negatively with the inhibitory function of Tregs (R = 0.398, P = 0.03), and Tregs function declined significantly in the high Tg group (Tg >77 μg/L) compared with the normal Tg group (11.4 ± 3.9% vs 27.5 ± 3.5%, P < 0.05). Compared with peripheral blood, the function of Tregs in thyroid declined significantly (P < 0.01), but the proportion of FOXP3+ Tregs in thyroid increased (P < 0.01). High concentration of Tg (100 μg/mL) inhibited the function of Tregs and downregulated FOXP3, TGF-β and IL-10 mRNA expression in Tregs in vitro.
Conclusions
Elevated Tg level could impair the function of Tregs, which might increase the risk of AITDs in patient with thyroid nodules.
Medical Science Laboratory, Children’s Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China
Department of pathology, Children’s Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China
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Department of pathology, Children’s Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China
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Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Background
The incidence of congenital hypothyroidism (CH) differs significantly among different ethnicities and regions, and early differentiation of transient CH is important to avoid unnecessary prolonged treatment with L-T4.
Objective
To investigate the incidence of CH based on the newborn screening program in Guangxi Zhuang Autonomous Region, China, and to analyze the predictors that might allow for an early differentiation between permanent (P) and transient (T) CH.
Design and methods
Data from newborn screening program over a seven-year period (January 2009 to January 2016) at Guangxi Maternal and Child Health Hospital are analyzed. Blood samples were collected on filter paper between 3 and 7 days after birth, and TSH level was measured by time-resolved fluorescence assay. Individuals with increased TSH (TSH ≥ 8 IU/L) levels detected by newborn screening were recalled for further evaluation. Serum TSH, FT3 and FT4 were determined by electrochemiluminescence assay using venous blood samples. Diagnosis of CH is based on elevated TSH levels (>10 IU/L) and decreased FT4 levels (<12 pmol/L). Patients with elevated TSH levels and normal FT4 levels were diagnosed as hyperthyrotropinemia. Permanent or transient CH was determined by using the results of thyroid function tests after temporary withdrawal of L-T4 therapy at approximately 2–3 years of age.
Results
Among 1,238,340 infants in the newborn screening program, 14,443 individuals were recalled for reevaluation (re-call rate 1.18%), 911 and 731 individuals were subsequently determined to have hyperthyrotropinemia and CH respectively; thus, a prevalence of 1:1359 and 1:1694 for hyperthyrotropinemia and CH. Of the 731 patients with CH, 161 patients were diagnosed with permanent CH (PCH), and 159 patients were diagnosed with transient CH (TCH), the other 411 patients are too young to determine their subtypes. Patients with PCH required an increasing dose of L-T4 during the first few years, whereas patients with TCH required a decreased dose of L-T4. The TSH levels at diagnosis and the dose of L-T4 used were significantly higher in PCH cases than in transient cases. The FT4 levels at diagnosis were significantly lower in PCH cases than in TCH cases. The TSH levels at diagnosis, FT4 levels at diagnosis and L-T4 doses at 90 days were evaluated as predictors for differentiating PCH and TCH, and their accuracy at their respective optimal cutoffs were determined to be 60.6%, 66.7% and 93.9%, respectively.
Conclusions
The CH incidence in Guangxi Zhuang Autonomous Region is slightly higher (1:1694) compared to the worldwide levels (1/2000–1/4000). The PCH and TCH ratio is close to 1; thus, the estimated PCH incidence is 1/3388, which is similar to reported worldwide average incidence (1/3000). The L-T4 dose required at 90 days (>30 μg/day) has the highest predictive value for PCH. Earlier differentiation of PCH and TCH helps to determine appropriate treatment course.
Department of Endocrinology, The People’s Hospital of Daxing District, Beijing, China
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Background
The pathogenesis underlying the alterations of orbital architecture in Graves’ orbitopathy (GO) is not yet fully understood. The present study aimed to investigate the association of DNA methylation in peripheral blood and orbital volumetry in Chinese patients with GO.
Methods
A total of 35 GO subjects (70 orbits) were subjected to CT scan. The total cross-sectional area of the extraocular muscles (orbital muscles, OM), total orbit area (TOA), and the exophthalmometry were measured and OM/TOA ratio was calculated. Targeted bisulfite sequencing was performed on seven candidate genes.
Results
No significant correlation was established between the DNA methylation levels of these genes and exophthalmometry. The MBP methylation level was found to be correlated with OM/TOA ratio (P < 0.05). Multiple linear regression analysis on parameters including age, sex, TRAb, duration of GO, and DNA methylation levels of seven genes with OM/TOA ratio confirmed that MBP and OM/TOA ratio had a significant correlation (P < 0.05). The partial least squares analysis showed that the top three genes with the highest loadings were MBP, BOLL, and BECN1 and that OM/TOA ratio affected the DNA methylation block than exophthalmometry.
Conclusions
This study provided preliminary evidence that MBP is a potential gene associated with OM enlargement in GO patients according to the combination of DNA methylation sequencing and orbital CT measurement.
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Objective
Clusterin is closely correlated with insulin resistance and its associated comorbidities. This study aimed to investigate the correlation between serum clusterin levels and non-alcoholic fatty liver disease (NAFLD) and further explore the mediating role of insulin resistance in this relationship.
Methods
This study enrolled 195 inpatients (41 males and 154 females) aged 18–61 years. Twenty-four patients were followed up for 12 months after bariatric surgery. Serum clusterin levels were measured using a sandwich enzyme-linked immunosorbent assay. Fatty liver disease was diagnosed on the basis of liver ultrasonography. The fatty liver index (FLI) was calculated to quantify the degree of hepatic steatosis. The mediating role of homeostasis model assessment-insulin resistance (HOMA-IR) was assessed using mediation analysis.
Results
Participants with NAFLD had significantly higher serum clusterin levels than those without NAFLD (444.61 (325.76–611.52) mg/L vs 294.10 (255.20–373.55) mg/L, P < 0.01). With increasing tertiles of serum clusterin levels, the prevalence of NAFLD displayed an upward trend (P < 0.01). Multivariate linear regression analysis showed that serum clusterin levels were a positive determinant of FLI (standardized β = 0.271, P < 0.001) after adjusting for multiple metabolic risk factors. Serum clusterin levels significantly decreased after bariatric surgery (298.77 (262.56–358.10) mg/L vs 520.55 (354.94–750.21) mg/L, P < 0.01). In the mediation analysis, HOMA-IR played a mediating role in the correlation between serum clusterin levels and FLI; the estimated percentage of the total effect was 17.3%.
Conclusion
Serum clusterin levels were associated with NAFLD. In addition, insulin resistance partially mediated the relationship between serum clusterin levels and FLI.
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Objective
To create a nomogram-based model to estimate the Chinese population's 5-year risk of metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods
We randomly divided 7582 participants into two groups in a 7:3 ratio: one group was assigned to work with the training set, which consisted of 5307 cases, and the other group was assigned to validate the model using 2275 cases. The least absolute shrinkage and selection operator model was employed to ascertain the variables with the highest correlation among all potential variables. A logistic model was constructed by incorporating these selected variables, which were subsequently visualized using a nomogram. The discriminatory ability, calibration, and clinical utility of the model were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).
Results
During the 5-year follow-up, 1034 (13.64%) total participants were newly diagnosed with MASLD. Using eight variables (gender, body mass index, waist, hemoglobin, alanine aminotransferase, uric acid, triglycerides, and high-density lipoprotein), we built a 5-year MASLD risk prediction model. The nomogram showed an area under the ROC of 0.795 (95% CI: 0.779–0.811) in the training set and 0.785 (95% CI: 0.760–0.810) in the validation set. The calibration curves revealed a 5-year period of agreement between the observed and predicted MASLD risks. DCA curves illustrated the practicality of this nomogram over threshold probability profiles ranging from 5% to 50%.
Conclusion
We created and tested a nomogram to forecast the risk of MASLD prevalence over the next 5 years.
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Purpose
To evaluate the value of MRI-based texture analysis of extraocular muscle (EOM) and orbital fat (OF) in monitoring and predicting the response to glucocorticoid (GC) therapy in patients with thyroid-associated ophthalmopathy (TAO).
Methods
Thirty-seven active and moderate-to-severe TAO patients (responders, n = 23; unresponders, n = 14) were retrospectively enrolled. MRI-based texture parameters (entropy, uniformity, skewness and kurtosis) of EOM and OF were measured before and after GC therapy, and compared between groups. Correlations between the changes of clinical activity score (CAS) and imaging parameters before and after treatment were assessed. Receiver operating characteristic curves were used to evaluate the predictive value of identified variables.
Results
Responsive TAOs showed significantly decreased entropy and increased uniformity at EOM and OF after GC therapy (P < 0.01), while unresponders showed no significance. Changes of entropy and uniformity at EOM and OF were significantly correlated with changes of CAS before and after treatment (P < 0.05). Responders showed significantly lower entropy and higher uniformity at EOM than unresponders before treatment (P < 0.01). Entropy and uniformity of EOM and disease duration were identified as independent predictors for responsive TAOs. Combination of all three variables demonstrated optimal efficiency (area under curve, 0.802) and sensitivity (82.6%), and disease duration alone demonstrated optimal specificity (100%) for predicting responsive TAOs.
Conclusion
MRI-based texture analysis can reflect histopathological heterogeneity of orbital tissues. It could be useful for monitoring and predicting the response to GC in TAO patients.
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Introduction
Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation.
Materials and methods
Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23–KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients.
Results
Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12.
Conclusion
Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.
