Evidence on joint association of a phthalate mixture with thyroid function among children and its underlying mechanism is largely unknown. We aimed to explore the associations of 10 urinary phthalate metabolites (mPAEs), either as individuals or as a mixture, with thyroid function indicators [free thyroxine, free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH)] in 144 children aged 4–12 years with up to 3 repeated visits across 3 seasons. Significant and positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) with TSH, as well as monobenzyl phthalate (MBzP) with FT3 in dose–response manners. The relationship between MEHP and TSH remained robust in multiple-phthalate models. Bayesian kernel machine regression (BKMR) models revealed overall linear associations of the 10 mPAE mixture with higher TSH and FT3 levels, and MEHP and MBzP were major contributors. Meanwhile, MEHP, MiBP, and MnBP were linked to the elevation of multiple cytokines including CCL 27, CCL3, CXCL1, and IL-16. Among them, IL-16 mediated the relationships of MEHP and MiBP with TSH, and the mediated proportions were 24.16% and 24.27%, respectively. Our findings suggested that mPAEs dominated by MEHP were dose-responsively associated with elevated TSH among healthy children and mediated by IL-16.

Purpose: This study aimed to investigate the value of combined detection of HCY and NRG4 in the diagnosis of early diabetic kidney disease (DKD) and to explore the association between the ratio of HCY/NRG4 and DKD. Methods: A total of 140 diabetic patients and 43 healthy people were prospectively enrolled. The plasma HCY level, NRG4 level and HCY/NRG4 of them were measured to compare their differences and analyze the correlation with DKD. The independent influencing factors of patients with DKD were screened, and the nomograph of DKD occurrence was constructed. Results: The levels of HCY and HCY/NRG4 in diabetic patients were significantly increased, while the level of NRG4 was significantly decreased (p < 0.01). The AUCs of HCY/NRG4 predicted for DKD were 0.961. HCY/NRG4 and the course of DM were independent risk factors for DKD. A predictive nomograph of DKD was constructed, and decision curve analysis (DCA) showed good clinical application value. HCY/NRG4 was positively correlated with Scr, UACR, TG, UA, BUN, TCHOL and LDL and negatively correlated with eGFR and HDL (p < 0.05). Conclusions: The level of HCY and NRG4 is closely related to the severity of DM, and combined detection of HCY/NRG4 can identify patients with DKD at an early stage.