Background: Ambient air pollution is closely related to a variety of health outcomes. Few studies have focused on the correlations between air pollution exposure and children’s sexual development. In this study, we investigated the potential effects of exposure to air pollution on precocious puberty among children using real-world evidence. Methods: We conducted a case-crossover study (n = 2201) to investigate the effect of ambient air pollution exposure on precocious puberty from January 2016 to December 2021. Average exposure levels of PM_2.5, PM₁₀, SO₂, NO₂, CO, and O₃ before diagnosis were calculated by using the inverse distance weighting (IDW) method. Distributed lag nonlinear model (DLNM) was used to assess the effect of air pollutants exposure on precocious puberty. Results: The mean age of the children who were diagnosed with precocious puberty was 7.47 ± 1.24 years. The average concentration of PM_2.5 and PM₁₀ were 38.81 ± 26.36 μg/m³ and 69.77 ± 41.07 μg/m³, respectively. We found that exposure to high concentrations of PM_2.5 and PM₁₀ might increase the risk of precocious puberty using the DLNM model adjusted for the age, SO₂, NO₂, CO, and O₃ levels. The strongest effects of the PM_2.5 and PM₁₀ on precocious puberty were observed in lag 27 (OR = 1.72, 95% CI: 1.01–2.92) and lag 16 (OR = 1.95, 95% CI: 1.33–2.85), respectively. Conclusion: Our findings supported that short-term exposure to air pollution was the risk factor for precocious puberty. Every effort should be made to protect children from air pollution.

Background: To date, the gonadotropin-releasing hormone (GnRH) stimulation test is still the gold standard for precocious puberty (PP) diagnosis. However, it has many disadvantages, including low sensitivity, high cost, and invasive operation. This study aims to evaluate whether magnetic resonance imaging (MRI)-derived variables, including pituitary volume (PV), could be used as diagnostic factors for PP in girls, providing a non-invasive diagnostic approach for PP. Methods: A total of 288 young female patients who presented to the Clinic of Pediatric Endocrinology for evaluation of PP from January 2015 to December 2017 were enrolled. The sample included 90 girls diagnosed with premature thelarche (PT), 133 girls determined as idiopathic central precocious puberty (ICPP), 35 early pubertal girls, and 30 normal girls. All patients received pituitary MRI examinations. Results: The largest PV and pituitary height were shown in the ICPP and pubertal groups, followed by the PT group. The receiver operating characteristic (ROC) curve analysis showed that PV is a predictive marker for ICPP, with a sensitivity of 54.10% and a specificity of 72.20% at the cutoff value of 196.01 mm³. By univariate analysis, PV was positively associated with peak luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), age, bone age, and body mass index (BMI) (all P < 0.05). However, bone age and peak LH were the only significant predictors of PV as demonstrated by the stepwise multivariate regression analysis (Model: PV = 9.431 * bone age + 1.230 * peak LH + 92.625 [P = 0.000, R² = 0.159]). Conclusions: The PV in the ICPP group was significantly higher than in PT and control groups, but there was no reliable cutoff value to distinguish ICPP from PT. Pituitary MRI should be combined with clinical and laboratory tests to improve the diagnostic value of PV for PP.

As a selective inhibitor of BRAF kinase, dabrafenib has shown potent anti‐tumour activities in patients with BRAFV600E mutant anaplastic thyroid cancer. However, the resistance of thyroid cancer cells to dabrafenib limited its therapeutic effect. The effects of melatonin and dabrafenib as monotherapy or in combination on the proliferation, cell cycle arrest, apoptosis, migration and invasion of anaplastic thyroid cancer cells were examined. The molecular mechanism involved in drug combinations was also revealed. Melatonin enhanced dabrafenib‐mediated inhibition of cell proliferation, migration and invasion, and promoted dabrafenib‐induced apoptosis and cell cycle arrest in anaplastic thyroid cancer cells. Molecular mechanistic studies further uncovered that melatonin synergized with dabrafenib to inhibit AKT and EMT signalling pathways. Furthermore, melatonin and dabrafenib synergistically inhibited the expression of hTERT, and the inhibition of cell viability and the induction of cell cycle arrest mediated by the combination of these two drugs were reversed by hTERT overexpression. Taken together, our results demonstrated that melatonin synergized the anti‐tumour effect of dabrafenib in human anaplastic thyroid cancer cells by inhibiting multiple signalling pathways, and provided new insights in exploring the potential therapeutic targets for the treatment of anaplastic thyroid cancer.

Objective: This cross-sectional study analyzed the clinical characteristics of newly diagnosed Graves' disease (GD) in children and adolescents to provide clinical evidence for the early diagnosis of GD.Method: From 2013 to 2019, information on children and adolescents with newly diagnosed GD admitted to the Department of Endocrinology, Children's Hospital of Nanjing Medical University, was collected, including clinical features and laboratory tests. The data were summarized and statistically analyzed.Result: This study included 204 cases of newly diagnosed GD, with 158 females and 46 males. The average age at initial diagnosis was 8.9 ± 2.9 years. A total of 132 cases (64.7%) had symptoms before puberty, and 72 cases (35.3%) had symptoms during puberty. Goiter was detected in 193 cases (94.6%). There were 140 cases (68.6%) of exophthalmos, and 21.4% (30/140) were infiltrative. At initial diagnosis, 10 cases (4.9%) reported leukopenia, 18 cases (8.8%) reported neutropenia, and 15 cases (7.4%) reported mild anemia. There was 1 (0.5%) case of thrombocytopenia and 1 (0.5%) case of agranulocytosis. Fifty-four cases (26.5%) had impaired liver function.Conclusion: GD is more common in female children and adolescents. Parents may ignore their children's hypermetabolic symptoms in the early stages of GD. Routine blood and liver function tests are recommended at initial diagnosis to exclude abnormal hemogram and liver function.

Background: The Sinovac enterovirus 71 (EV71) vaccine has shown good safety, immunogenicity, and efficacy in infants aged 6–35 months, whom are considered as the priority of the target population. However, 3–5 years old children accounted for approximately 30% of HFMD cases and are also worth our attention. Methods: A randomized, double-blind, placebo-controlled, batch-to-batch consistency clinical trial enrolling 1400 participants aged 6–59 months was performed. We pooled the participants receiving three batches of EV71 vaccine together and then stratified them into the 6–35 months and 3–5 years. The non-inferiority analysis of the geometric mean titer (GMT) of EV71 neutralizing antibody post-vaccination was the primary endpoint. Results: In the vaccine group, the GMT of 242 children aged 3–5 years was 132.72 (95% CI, 110.3–159.6), which was non-inferior to that generated in 717 infants aged 6–35 months. Following the vaccination, the incidence of adverse reactions was less frequent in children aged 3–5 years (47.0%) than that found in infants aged 6–35 months (60.1%) (p = 0.0026). Conclusions: Our study indicated that the EV71 vaccine was also safe in children aged 3–5 years, with non-inferior immunogenicity to that in infants aged 6–35 months.

Objective: 11β-hydroxylase deficiency (11βOHD) is a rare autosomal recessive disorder caused by mutations in the CYP11B1 gene. It is characterized by virilization, hypertension, and significant final height impairment. In this study, we aim to investigate the clinical and molecular characteristics of four unrelated Chinese patients with 11βOHD disorder. Methods: The clinical information of four 11βOHD patients were carefully reviewed. Genetic analysis was performed using next-generation sequencing (NGS) based panel analysis. NGS coverage depth was analyzed to detect exonic copy-number variants (CNVs) on patient 1. Quantitative PCR (qPCR) was subsequently performed to confirm the CNVs detected from the NGS coverage depth analysis. Results: The mean age of the patients at diagnosis was 4.7 years (range, 2.0–9.3 years). Two genetically female patients (patients 1 and 2) with 11βOHD presented severe virilization of external genitalia and were raised as males. Two genetically male patients (patients 3 and 4) presented precocious puberty. Additionally, patients 1, 3, and 4 presented with hypertension. In patient 4, unilateral adrenal mass was detected and removed at the age of 9 years. Interestingly, the height of patient 4 (174.4 cm, +6.7 SD) wasn't impaired and reached his mid-parental height (173 cm). Three novel variants in the CYP11B1 gene (c.1150_1153del, c.217C>T, and c.400G>C) were identified by NGS. Various bioinformatics tools revealed potential pathogenic effects for the novel variants, and evolutionary-conservation revealed that the novel missense variant affected an amino acid that is highly conserved among species. Furthermore, NGS coverage depth analysis and qPCR identified a novel heterozygous deletion of exons 1–6 in patient 1. Conclusion: Our study expands the spectrum of mutations of the CYP11B1 gene in Chinese population. In addition, We reported the first case of a patient with classical 11βOHD disorder, whose final height wasn't compromised.