Primary intracranial choriocarcinoma (PICCC) is a rare, highly malignant non-germinomatous germ cell tumor (NGGCT), primarily affecting children and adolescents with a male predominance. It most commonly arises in the pineal region and sella turcica. This report describes a case of primary choriocarcinoma in the pineal region. CT imaging revealed a patchy area of abnormal high density with slight internal density variation and small nodular calcifications. MRI showed a mixed signal pattern, predominantly slightly short T1-weighted and short T2-weighted signals. Contrast-enhanced imaging demonstrated heterogeneous enhancement. Surgical pathology specimens showed immunohistochemical positivity for HCG(+), HPL(+), CK(PAN)(+), EMA(partial+), p53(partial+), PLAP(placental alkaline phosphatase, partial+), CD117(partial+), and Ki-67 proliferation index: 20%. The pathological findings were consistent with pineal region choriocarcinoma. The patient’s serum β-HCG level decreased to <0.1 mIU/mL one year after surgery, and the child remained in good condition without recurrence during the 2-year follow-up.

BACKGROUND: While numerous studies have examined associations between prenatal air pollution exposure and fetal growth measures, investigations assessing longitudinal growth trajectories across multiple time points during mid-to-late pregnancy remain limited. OBJECTIVES: The aim of this study is to explore the effects of prenatal exposure to air pollution on fetal growth trajectories. METHODS: From a prospective birth cohort in Wuhan, China, recruited from 2013 to 2016, we included a total of 4283 eligible pregnant women. At 16, 24, 31, and 38 weeks of gestation, we collected ultrasound measurements, including biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Exposure to air pollution during pregnancy was estimated for the participants' residential addresses using a spatial interpolation method. Associations between air pollutants and fetal growth parameters across four exposure windows were examined by using multiple informant models. Group-based trajectory modeling (GBTM) combined with a multinomial logistic regression model was used to explore the effect of air pollution exposure on fetal growth trajectories. RESULTS: Four trajectory groups for AC, FL, and EFW, and three trajectory groups for BPD were selected based on GBTM. Compared with the reference trajectory group, exposure to higher PM2.5 during weeks 1-16 was significantly associated with lower odds of being in the "fast growth group" for AC (OR = 0.68, 95% CI: 0.55, 0.84) and EFW (OR = 0.71, 95% CI: 0.56, 0.91). Exposures to PM2.5, PM10, NO2, SO2, and CO during 1-16 weeks were negatively associated with AC, FL, and EFW at 16 weeks as well as BPD, FL, and EFW at 24 weeks. Similar negative associations were observed between air pollution exposure during 25-38 weeks and AC and EFW at 38 weeks. DISCUSSION: Our study provided evidence of negative associations between air pollution exposure during 1-16 weeks of gestation and the fast growth trajectory group. In addition, we observed distinct lagged associations between air pollution and fetal growth, with early pregnancy exposure negatively related to early and midgestational growth, and mid-to-late pregnancy exposure negatively related to growth in the late window. These results underscore the importance of identifying critical windows of susceptibility during pregnancy and support early intervention strategies to mitigate adverse fetal developmental outcomes.

The prediction of fetal age based on fetal magnetic resonance imaging (MRI) is widely used to describe normal fetal brain development, with edge contours of the sulcus and gyrus crucial for brain maturity. However, neural network learning can cause loss of edge information during downsampling. To address this issue, our research team introduced the concept of edge guidance to compensate for the loss of edge information in the downsampling process of the network. EGMA-Net consists of three branches: the original image branch, the edge image branch, and the fusion branch. Hierarchical-Split Residual Network (HS-ResNet) serves as the foundational network for both the original image and edge image branches, with intermediate results aiding in network learning. In the fusion branch, a layer-level fusion strategy combines original image features and edge image features using attention fusion. This approach concentrates the network on brain spatial coordinates, mitigating challenges from angular deviations and motion artifacts in MRI images. Tested on 1327 MRI images of 157 fetuses at 22 to 34 weeks from Wuhan Children’s Hospital, EGMA-Net achieves an average absolute error of 0.741 weeks and an R2 value of 0.907. These results indicate that the method is helpful for fetal development assessment and prenatal diagnosis.

Maternal exposure to thallium may cause fetotoxicity in offspring. However, epidemiological studies on the neurodevelopmental toxicity associated with early-life thallium exposure are limited, and the underlying mechanisms remain ambiguous. Based on a prospective longitudinal birth cohort study in Wuhan, China (n = 1036), we quantified maternal thallium concentrations in spot urine samples collected during late pregnancy. Metabolomics analyses were performed on cord blood plasma samples collected at birth. Offspring neurodevelopment, characterized by mental developmental index (MDI) and psychomotor developmental index (PDI), was assessed at 2 years of age. Maternal thallium levels, modeled as either continuous or categorical variables, demonstrated significant inverse associations with children's MDI and PDI scores. Each unit increase in thallium was linked to a 2.66-point decrease (95 % CI: -4.02, -1.30) in MDI scores and a 1.79-point decrease (95 % CI: -2.92, -0.65) in PDI scores. The inverse relationships were further confirmed across tertiles of thallium exposure, and linear dose-response associations were observed. Metabolomics analysis revealed that perturbations in multiple amino acid and lipid metabolism, involving differential metabolites and related pathways such as 4-hydroxyproline, 5-hydroxylysine, and fatty acids, exerted significant mediating effects on the observed inverse associations. Our study provides novel evidence linking maternal thallium exposure to adverse offspring neurodevelopment and highlights metabolic disturbances as important underlying biological mechanisms for this association.

PURPOSE:Cancer and its treatment-related effects may impair fertility and increase reproductive concerns (RCs) among adolescent and young adult (AYA) survivors at their peak reproductive years. To assess RCs in survivors and examine their associated factors and pathways. METHODS:A cross-sectional study was conducted with 209 AYA cancer survivors aged 15-39 years from June 2023 to December 2024. Participants' RCs, cancer-related sexual and reproductive health knowledge, attitudes, and needs were measured. Multiple linear regression and structural equation modeling were performed. RESULTS:Participants' mean RCs score was 70.17 ± 6.70. Regression showed that cancer-related sexual and reproductive health attitudes (B = 0.646, p < 0.001), needs (B = 0.516, p = 0.001) were positively associated with RCs. Awareness of fertility preservation options, including sperm donation (B = 2.034, p = 0.005) and testicular replacement (B = 2.224, p = 0.044), was also positively associated with RCs. Conversely, endorsement of artificial uterus technology (B = -3.032, p = 0.007), perceived impact of habitual sleep deprivation on fertility (B = -1.491, p = 0.030), and a history of hematologic malignancy (B = -6.256, p = 0.003) were negatively associated with RCs. Structural equation modeling showed that attitudes (β = 0.531, p < 0.001), knowledge (β = 0.201, p = 0.003), and needs (β = 0.295, p = 0.006) were significantly associated with RCs. CONCLUSIONS:RCs among AYA cancer survivors are associated with sexual and reproductive health-related attitudes, knowledge, needs. Integrated education and supportive care may be relevant for addressing RCs in this population.

The neurotoxicity of emerging contaminants, polyhalogenated carbazoles (PHCZs), is elusive. In this study, we investigated the potential toxicity of 13 prevalent PHCZs utilizing a network toxicology approach, which revealed shared molecular targets associated with Parkinson's disease (PD). Molecular docking simulations assessed the binding affinities of these PHCZs for eight key PD-related targets, identifying monoamine oxidase B (MAOB) as a critical target. Among the dihalogenated PHCZs, 2,7-dibromocarbazole (2,7-BCZ) exhibited the highest binding affinity to MAOB. Comparative molecular docking and dynamics simulations suggest that the inhibition of MAOB activity by 2,7-BCZ is a potential initiating event in PHCZ-induced neurological disorders. In vivo experiments confirmed that 2,7-BCZ exposure highly correlates with α-synuclein aggregation, a hallmark of PD pathology. Transcriptomic sequencing of 2,7-BCZ-exposed SH-SY5Y cells, combined with analysis of public PD microarray data, identified shared transcriptional alterations in genes including CLSTN2, CBLN1, AGTR1, DLK1, and DDC. By integrating pathways from PD-related targets of PHCZs, differentially expressed genes in 2,7-BCZ-exposed cells, and public PD data sets, we further elucidated key biological pathways through which 2,7-BCZ may contribute to PD pathogenesis, particularly dopaminergic synapse function and neurodevelopmental regulation. Collectively, this study not only highlights the potential role of PHCZs in PD, elucidating the potential biological mechanisms by which PHCZs may exacerbate PD, but also exemplifies an innovative, animal-sparing approach using New Approach Methodologies (NAMs) to assess environmental pollutants' risks in neurodegenerative adverse outcomes.

Herbicides such as chloroacetamides, chlorophenoxy acids, triazines, and bentazone are widely used in agriculture, contaminating aquatic ecosystems. However, their distribution and ecological risks in the Yangtze River are not clear. Thus, we analyzed 144 surface water samples (72 each in dry and wet season, respectively) collected from 72 sites along the Yangtze River mainstream, targeting 37 compounds, including these herbicides and their transformation products. Most compounds (31/37) were detected in > 90% of the samples. The dominant compounds were acetochlor oxanilic acid (median: 30.5 ng/L), atrazine (15.4), acetochlor ethanesulfonic acid (14.7), acetochlor (5.53), 2-methyl-4-chlorophenoxyacetic acid (5.27), followed by diaminochlorotriazine (4.72), bentazone (4.47), hydroxypropazine (3.93), prometryn (3.50), metolachlor (3.14), deethylatrazine (3.11), and others. The concentrations of the target compounds significantly increased from upstream to downstream; for example, the cumulative concentration in Shanghai (median: 660 ng/L) was approximately 300 times higher than that in Qinghai (2.18 ng/L). Significant seasonal variation was observed, with higher cumulative concentration in June (median: 198 ng/L) than December (63.9 ng/L; p < 0.05). The ecological risk assessment indicated that pretilachlor, acetochlor, prometryn, hydroxypropazine, hydroxyterbuthylazine, and butachlor oxanilic acid posed high risks (risk quotient of > 1) to aquatic organisms in some sampling sites. This study is the first to report the occurrence of some transformation products of the herbicides (e.g., hydroxysimazine, 4-chlorophenoxyacetic acid, and hydroxylated chlorophenoxy acids) in river water. Our findings highlighted the widespread occurrence of the herbicides in the Yangtze River, and targeted pollution mitigation for pretilachlor, acetochlor, prometryn and their transformation products is urgently needed, especially in the downstream reaches including Jiangsu and Shanghai, to protect the aquatic organisms.

Baby swimming is a widely practiced early childhood healthcare activity, but its long-term health outcomes remain unclear. This study aimed to investigate whether baby swimming participation during the first six months of life is associated with intellectual development at preschool age. Children from the Wuhan Healthy Baby Cohort who completed follow-up questionnaires at 1 and 6 months and intelligence quotient (IQ) assessments between March 2022 and November 2023 were recruited. Based on baby swimming data, children were classified by participation status (participation, non-participation) and period (none, birth to 1 month, 1 to 6 months, and birth to 6 months). IQ was assessed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition at 4 to 6 years old. Generalized linear and logistic regression models assessed the association between swimming and IQ, with stratified analyses for maternal and infant-related factors. We included 1935 mother–child pairs, with 1272 children (65.7%) participating in baby swimming. Participants had higher scores in full-scale IQ (FSIQ) [β (95%CI): 2.46 (1.35, 3.57)], verbal comprehension index (VCI) [1.64 (0.35, 2.92)], visual-spatial index (VSI) [2.15 (0.76, 3.54)], fluid reasoning index (FRI) [2.48 (1.44, 3.51)], and working memory index (WMI) [1.75 (0.62, 2.87)]. Higher IQ scores were observed in the “1 to 6 months” and “birth to 6 months” groups. Point estimates were numerically higher among boys and children from higher socioeconomic status (SES) families. Participation in baby swimming during the first 6 months was associated with higher preschool intellectual development scores, especially among boys and children from higher SES families. These findings support further research on early-life aquatic activity and neurodevelopment.

Neonicotinoid insecticides (NNIs) are globally prevalent environmental contaminants with suspected endocrine-disrupting properties, yet their effects on maternal steroid hormone homeostasis and the subsequent risks of precocious puberty (PP) in offspring remain poorly understood. In this prospective nested case-control study embedded in a birth cohort in Wuhan, China (2012-2014; follow-up to 2023), we included 202 PP cases (115 incomplete [ICPP], 87 central [CPP]) and 606 matched controls. Third-trimester maternal urine samples were analyzed for 19 NNI biomarkers (8 detected in ≥74.1% of the samples) and 12 steroid hormones. Higher maternal urinary imidacloprid (IMI) and metabolites were significantly associated with increased odds of ICPP, but not CPP. Mixture analyses using generalized weighted quantile sum regression and Bayesian kernel machine regression consistently showed positive associations between exposure to the NNIs and ICPP odds, with 5-hydroxy-IMI identified as the major contributor (46.8%). NNI exposure was linked to altered maternal steroid hormone profiles, with more pronounced disruptions in ICPP case mothers. Exploratory mediation analysis suggested that progesterone (P4) and 17α-hydroxyprogesterone (17α-OHP) may partially mediate the association between IMI exposure and ICPP, accounting for 27.6% and 20.2% of the total effect, respectively. These findings suggest that prenatal IMI exposure may elevate the odds of ICPP in girls, potentially through disruption of maternal steroid hormone homeostasis, underscoring the need for public health attention to mitigate the developmental risks of NNI exposure during vulnerable windows.

Organophosphate (OPPs), pyrethroids (PYR), and neonicotinoid (NNIs) insecticides are widely used chemicals that may disrupt endocrine function. However, the effects of prenatal co-exposure on maternal and infant reproductive hormones remain unclear. In a prospective cohort of 846 mother-infant pairs, we measured five OPPs metabolites (mOPPs), three PYRs metabolites (mPYRs), and ten NNIs and their metabolites (mNNIs) in maternal urine; eight steroid reproductive hormones in maternal and infant urine; and two gonadotropins in infant urine. Individual insecticides were associated with increased maternal hormones, with the greatest increase in 17α-OH-progesterone (67.29 %; 95 % CI: 56.03 %, 79.36 %). Quantile-based g-computation analysis showed that overall and class-specific mixtures were associated with elevated maternal hormones, especially dihydrotestosterone (an androgen) (β: 0.54; 95 % CI: 0.45, 0.64). Conversely, several mOPPs and mNNIs were associated with lower infant hormone levels, most notably a reduction in progesterone (-10.85 %; 95 % CI: -20.43 %, -0.10 %). The total mixture was linked to decreased infant progesterone (β: -0.13; 95 % CI: -0.25, -0.01), while the mOPPs mixture was associated with reduced androstenedione (an androgen) (β: -0.07; 95 % CI: -0.13, -0.00). Compared to the low insecticides cluster, the high insecticides cluster and the high mNNIs cluster were associated with higher maternal progestogens (progesterone (β: 0.32; 95 % CI: 0.03, 0.61); 17α-OH-progesterone (β: 0.25; 95 % CI: 0.03, 0.47)). Elevated maternal progesterone had a suppressive mediation effect on the negative association between specific mNNIs (desmethyl-acetamiprid and clothianidin) and progesterone in male infants (proportion >15 %). These findings demonstrated that prenatal insecticide exposure, whether analyzed individually, as mixtures, or by co-exposure clusters, was associated with increased maternal reproductive hormone levels and reduced levels of specific infant hormones, highlighting the need for further research into the long-term health implications.

Organochlorine pesticides (OCPs), banned decades ago due to their environmental persistence and toxicity, countinue to be detected as residual DDTs and HCHs in human populations. Previous studies suggest that prenatal exposure to OCPs may impair neurodevelopment in offspring, but the evidence remains inconsistent, especially regarding specific isomers, such as α-HCH and γ-HCH, which have rarely assessed in humans. This study investigated the association between prenatal OCP exposure and early childhood neurodevelopment, and explored the potential sex-specific effects. We measured HCH isomers (α-HCH, β-HCH, γ-HCH), DDT isomers (p,p'-DDT, o,p'-DDT), and DDT metabolites (o,p'-DDD, o,p'-DDE, p,p'-DDD, p,p'-DDE) in cord serum from 447 mother-child pairs in a birth cohort study in Wuhan, China (2014-2015). Neurodevelopment was assessed at age 2 with the Bayley Scales of Infant Development, which generated mental development index (MDI) and psychomotor development index (PDI) scores. Associations were evaluated using linear regression and weighted quantile sum (WQS) regression, with analyses stratified by sex. Most OCPs were detectable in over 50 % of samples, with median concentrations of 39.5 ng/g lipid for ∑DDTs and 10.8 ng/g lipid for ∑HCHs. Higher cord serum OCP concentrations were associated with lower MDI scores. An interquartile range (IQR) increase in γ-HCH was linked to a 2.45-point decrease in MDI (95 % CI: -4.76, -0.14) in all children, although this association did not remain significant after FDR correction. In girls, inverse associations were observed for α-HCH (-4.54 points; 95 % CI: -7.55, -1.53), γ-HCH (-5.20 points; 95 % CI: -8.04, -2.36), and p,p'-DDD (-5.25 points; 95 % CI: -9.97, -0.53). In mixture analyses, each quartile increase in OCP mixture was associated with a 6.10-point decrease in MDI and a 6.46-point decrease in PDI in girls, with γ-HCH (51.2 %) and p,p'-DDT (35.6 %) identified as the largest contributors. The results indicate that prenatal exposure to certain OCPs, particularly γ-HCH and p,p'-DDT, is associated with poorer neurodevelopment in early childhood, especially in girls. The findings highlight the need to address persistent OCP exposure and its developmental impacts.

Pregnancy complications pose a major hazard to maternal and fetal health and increase the global burden of disease. Phthalates are extensively encountered by pregnant women. To estimate associations of individual phthalate or mixture exposure in early pregnancy with pregnancy complications, a nested case-control study was conducted, in which cases with gestational diabetes mellitus (GDM), gestational hypertension (PIH), premature rupture of membranes (PROM), placental abnormality (PA), intrauterine distress (IUD), insufficient amniotic fluid (IAF), anemia and preterm birth (PB) were matched with controls by fetal sex, maternal age, sampling year and season, and measured urinary phthalate metabolites in the first trimester. Conditional logistic regression and quantile g-computation models were employed to assess associations of individual phthalate and mixture exposure with pregnancy complications. The conditional logistic regression revealed that certain phthalate exposure in early pregnancy was notably associated with higher risks of pregnancy complications, especially GDM, PIH, and IAF. For example, compared with the 1st tertile, the 2nd and 3rd tertiles of exposure were significantly associated with elevated odds of GDM, PIH, and IAF, with ORs of 1.40-1.76 and 1.38-2.98, 1.41-1.67 and 1.36-2.05, and 2.17-3.17 and 1.97-2.54, respectively. Moreover, these associations varied by fetal sex. Additionally, quantile g-computation models showed that phthalate mixture exposure was significantly associated with elevated ORs of GDM (OR = 1.32; 95% CI: 1.09, 1.74), PIH (OR = 1.49; 95% CI: 1.04, 1.78), and IAF (OR = 1.73; 1.06, 2.47). MBP and DEHP metabolites were likely the major contributors to the joint effects. Prenatal phthalate exposure during early pregnancy may serve as a potential risk factor for pregnancy complications. Further studies are essential to validate these findings.

Introduction: Early identification for preventing drug misuse among adolescents and young adults (AYAs) is more cost-effective than drug treatment. However, there is a lack of scientific and comprehensive risk models for early identification. This study aimed to construct risk models and association pathways that integrate psychosocial factors influencing drug misuse in AYAs using a machine learning approach. Methods: This cross-sectional study included 1,012 Chinese AYAs aged 14-35 years and was conducted from June to December 2023. Key psychosocial factors for drug misuse were identified using the least absolute shrinkage and selection operator and Boruta. A voting classifier combining logistic regression, K-nearest neighbors, support vector machine, and 5-fold cross-validation was used for model training and bootstrapping method wan applied for testing. Shapley additive explanation was used to determine the importance of each risk factor. A Bayesian network (BN) model was constructed to explore possible association pathways for drug misuse. Results: A total of 3.85% of participants reported drug misuse. Significant risk factors included environmental exposure to drug misusers, working in nightlife venues (WNVs), cognition of traditional drug types, perceived risks of drug misuse, permissive attitude toward drug misuse, refusal self-efficacy of drug misuse (RSEDM), externalizing problem behavior, sensation-seeking, and adverse childhood experiences (ACEs). The voting model showed strong performance (recall: 94.10%; area under the curve: 98.11%; accuracy: 92.63%; precision: 34.15%; F-score: 49.68%). The BN model revealed that ACEs played a central role in risk assessment of drug misuse. AYAs WNVs, with low RSEDM and exposure to drug misusers, had exceeding 90% probability of drug misuse. Conclusion: ACEs serve as a primary risk factor, with a significant impact on social environmental influences. AYAs with ACEs and those WNVs require targeted and early interventions to prevent drug misuse.

BackgroundExtragonadal yolk sac tumors are exceedingly rare. This report describes a vaginal yolk sac tumor in an infant to highlight key diagnostic and therapeutic aspects and its inclusion in the differential diagnoses of unexplained vaginal masses.Case presentationAn 11-month-old girl presented with intermittent vaginal bleeding, initially misdiagnosed as a hematoma. Pathological examination confirmed yolk sac tumors. She underwent hysteroscopic resection and six cycles of PEB (bleomycin, etoposide, cisplatin) chemotherapy. No recurrence occurred during the 12-month follow-up.ConclusionPrimary vaginal yolk sac tumors are extremely rare and lack standardized treatment. Surgery combined with PEB chemotherapy proved effective in this case.

Emerging evidence implicates neuroinflammation in the pathogenesis of major depressive disorder (MDD), yet the role of memory B cells remains unclear. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) study and Bayesian colocalization analyses to investigate the causal relationships between memory B-cell traits and MDD risk. MDD summary data were gathered from a meta-analysis of genome-wide association studies (GWASs), whereas memory B-cell genetic variations were sourced from GWASs on immune phenotypes. MR analysis utilized the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Moreover, various sensitivity analyses, including Cochran’s Q test, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), MR-Egger intercept test and Leave-one-out (LOO) analysis, were performed to confirm MR result stability. Bayesian colocalization analyses were also conducted to identify genetic loci shared between memory B cells and MDD. Our results indicated that genetically predicted increased CD27 protein expression on memory B cells causally elevated MDD risk (ORs: 1.025–1.063, PFDR < 0.05). Conversely, MDD did not causally affect memory B-cell traits. Additionally, the colocalization analysis revealed no shared genetic variants, suggesting distinct biological pathways. These findings highlight CD27 as a potential novel biomarker and therapeutic target in MDD, warranting further clinical validation in the future.

BackgroundTobacco use remains a leading cause of preventable morbidity and mortality worldwide. While smoking prevalence has recently declined in Hong Kong, progress has slowed. Plain packaging may reduce product appeal and enhance the impact of pictorial health warnings (PHWs), supporting reduced tobacco use.MethodsA cross-sectional study was conducted from August to November 2023 among 1,256 adult smokers in Hong Kong. Participants were recruited at outdoor public smoking hotspots and shown branded and plain cigarette packs with 85% PHWs. Perceptions of pack attractiveness, noticeability of PHWs, smoking-related harm, behavioural intentions, and support for plain packaging were assessed through structured interviews. Quantitative data were weighted by age and sex, and qualitative responses were analysed thematically.ResultsMost participants perceived plain packs as less attractive (79.8%) and PHWs on plain packs were more noticeable (57.5%) than branded packs. About 45.1% perceived plain packs as disgusting, and 28.0% agreed they better conveyed severe smoking harms than branded packs. While only 17.3% reported plain packs may reduce their intention to smoke, 33.1% reported that it could deter youth from smoking. Support for plain packaging was moderate, with 35.7% in favour and 34.5% neutral. The qualitative findings reinforced these perceptions.ConclusionSmokers perceived plain packaging as less attractive, the PHWs on it as more noticeable, and potentially useful in preventing smoking initiation in youth. These findings support the integration of plain packaging into Hong Kong’s tobacco control strategy and offer valuable insights for jurisdictions considering similar legislation.

Due to regulatory restrictions, traditional metabolites of phthalates [e.g., di-(2-ethylhexyl) phthalate] are being replaced by alternatives such as di-(isononyl)-cyclohexane-1, 2-dicarboxylate and di(2-propylheptyl) phthalate. The metabolites of the alternatives are frequently detected in human urine, but their association with potential health outcomes remain largely unknown. Epidemiological evidence linking perinatal exposure to traditional phthalates and their emerging alternatives with precocious puberty (PP) in girls remains sparse, and possible differences in their effects on clinical subtypes are unknown. This study aimed to analyze the association of maternal exposure to phthalates and their alternatives during pregnancy with PP odds in female offspring, assess subtype-specificity for incomplete precocious puberty (IPP, gonadotropin-independent) and central precocious puberty (CPP, gonadotropin-dependent), and explore the role of steroid hormones in the association and effect modification by maternal vitamin supplementation. We included 87 cases of CPP, 115 cases of IPP, and 606 matched controls in this (nested case-control) study based on the Wuhan Healthy Baby Cohort. Twenty-five metabolites of phthalates/alternatives (mPAEs) and thirteen steroid hormones were measured in maternal urine samples collected during late pregnancy. We employed multivariable logistic regression, Bayesian kernel machine regression (BKMR), and quantile-based g-computation (qgcomp) to assess single and mixture effects. Mediation analyses were used to evaluate the roles of the steroid hormones in the association, and subgroup analyses were used to evaluate the modification effect of vitamin supplementation. Higher maternal mono-methyl phthalate (MMP) level in the highest quartile (Q4) was related with elevated PP odds (Q4 vs. the lowest quartile, Q1: OR = 3.15; 95% CI: 1.57, 6.25). The associations were significantly specific to IPP, involving MMP (Q4 vs. Q1: OR = 3.07; 95% CI: 1.45, 6.48), metabolites of diisononyl phthalate [mono-(4-methyl-7-hydroxy-octyl) phthalate and mono-(4-methyl-7-oxo-octyl) phthalate], and a phthalate alternative metabolite [mono-(6-oxo-2-propylheptyl) phthalate]. No significant associations were observed for CPP. Mixture analysis identified MMP as the primary contributor (19%). progesterone (P4) mediated 34% of the MMP-IPP association. Crucially, maternal vitamin supplementation appeared to attenuate the adverse associations between the mPAEs and PP. Perinatal exposure to specific phthalates is associated with elevated odds of PP in girls, with stronger effects in the IPP subtype. The association may be partially mediated by altered maternal P4 levels. Our findings also suggested, for the first time, that maternal vitamin supplementation might mitigate these odds. This is also the first time to report the association between the metabolites of phthalate alternatives and PP odds.

Few studies have explored the association of prenatal exposure to typical endocrine disrupting chemicals such as nonylphenol (NP) and bisphenols with the odds of precocious puberty (PP) in girls. To evaluate the associations of maternal exposure to NP and bisphenols during pregnancy with the odds of PP [including central PP (CPP) and incomplete PP (IPP) subtypes] in girls, this study included 87 CPP cases, 109 IPP cases, and 588 matched (1: 3) controls based on a Wuhan birth cohort (2012-2014). Maternal urinary concentrations of three bisphenols and two NP metabolites [including oxo-NP and hydroxy-NP (OH-NP)] were measured before delivery. Multivariable logistic regression and weighted quantile sum regression were applied to evaluate the relationships of the individual phenols and their mixture with the PP odds in the girls. Non-linear dose-response relationships were observed between oxo-NP and OH-NP and the PP odds (p for non-linearity <0.05). Specifically, after false discovery rate (FDR) correction, the third quartile of OH-NP [odds ratio (OR): 1.42, 95 % confidence interval (CI): 1.09-1.87; pFDR = 0.01] and oxo-NP (OR: 1.52, 95 % CI: 1.17-1.98; pFDR = 0.002) showed significant associations with the overall PP odds. For PP subtypes, oxo-NP was significantly associated with CPP (the third quartile OR: 1.77, 95 % CI: 1.17-2.68; pFDR = 0.04). NP metabolites were identified as the major contributors to the phenol mixture associated with the CPP odds. Prenatal NP exposure may non-linearly increase the odds of PP in girls, particularly that of CPP, at moderate exposure levels, underscoring the need to reduce prenatal exposure and clarify the underlying mechanisms.

The rising incidence of childhood metabolic disorders poses an increasingly serious public health challenge. The developmental programming of the gut microbiota during early life, shaped by perinatal and postnatal factors, establishes a functional trajectory that profoundly influences host metabolism, with microbiota-derived metabolites serving as critical bridging molecules that mechanistically link early-life exposures to metabolic outcomes in childhood. Key microbiota‒metabolite pathways underpin this process, including the fermentation of dietary fiber into short-chain fatty acids (SCFAs), the microbial metabolism of amino acids into both protective and detrimental products, the biotransformation of primary bile acids (BAs) into secondary BAs, and the generation of trimethylamine N-oxide (TMAO) from methylamine precursors. These metabolites exert their effects through diverse molecular mechanisms, spanning epigenetic regulation and receptor signaling (including farnesoid X receptor [FXR], G protein-coupled bile acid receptor 1 [TGR5], and other metabolite-sensing receptors). A deep understanding of these microbiota-derived metabolites in the context of developmental programming is therefore essential not only for advancing precise diagnosis and personalized treatment but also for informing early and targeted prevention strategies to reduce the burden of childhood metabolic diseases.

Breast cancer (BC) metastasis is a serious concern in BC treatment. Early diagnosis and prompt intervention are extremely important for patients. Alterations in epigenetic modifications of circulating free DNA (cfDNA) have been reported during BC occurrence, but not before or after metastasis. Therefore, this study aimed to establish a highly metastatic 4T1 BC mouse model closely resembling stage IV human BC to explore changes in cfDNA methylation modifications before and after metastasis. The timing of BC metastasis was defined based on the first visible fluorescence detection in axillary lymph nodes using in small-animal imaging. The results showed that the methylation levels of CDH1 and Gjb1 in serum cfDNA changed significantly in BC before and after metastasis, displaying trends analogous to those observed in tumor tissue DNA. The methylation levels of cfDNA can be used as candidate biomarkers for the early diagnosis and monitoring of BC metastasis.