[This corrects the article DOI: 10.3389/fpubh.2025.1654356.].

Humans are widely exposed to environmental pollutants, affecting glucose homeostasis and resulting in gestational diabetes mellitus (GDM). However, studies about joint exposure of heavy metals and glucose homeostasis during pregnancy are limited and with the inconsistent findings. Blood concentrations of mercury (Hg), arsenic (As), lead (Pb), copper (Cu), vanadium (V), beryllium, strontium, zinc, nickel, cobalt, chromium, titanium, aluminum, antimony and iron were measured using inductively coupled plasma-mass spectrometry among 251 GDM women and 502 matched controls from Taiyuan, China. Multivariate logistic regression models, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quartile g-computation regression (QGCOMP) were used to assess the associations between metals exposures, maternal glucose homeostasis and GDM. An increased risk of GDM was associated with As, Pb and Hg in 1st trimester. Furthermore, exposure to Cu and Hg were associated with an elevated risk of GDM in 2nd trimester. The BKMR, WQS regression, and QGCOMP all found metals mixture exposure, predominated by Hg, As, and Pb in 1st trimester, was positively associated with GDM. The WQS regression revealed a positive correlation between metals characterized by Hg, Cu and As and GDM in 2nd trimester. The risk on GDM from joint metals was predominated by Hg, As, and Pb in 1st trimester, and by Hg, Cu, and As in 2nd trimester.

​Abstract Background: Infants born to HBsAg-positive mothers who fail to respond to hepatitis B vaccine (hepB) are at high risk of HBV infection. We aimed to identify miRNAs in cord blood mononuclear cells (CBMCs) as non-invasive biomarkers for predicting no response to hepB.Method: This prospective cohort study enrolled 367 mother-neonate pairs. CBMCs were analyzed via miRNA sequencing (n=16) and validated by RT-qPCR (n=128). SMOTE was applied to address class imbalance. The impact of miRNAs on no response to hepB was assessed using multivariate regression, restricted cubic spline regression and subgroup analysis. Predictive models were constructed using random forest, XGBoost, SVM, logistic regression and compared through AUC, sensitivity, negative predictive value.Results: The miR-183-5p and miR-486-5p were upregulated in the no response group through miRNA sequencing and RT-qPCR. The elevated expression of miR-183-5p and miR-486-5p in CBMCs increased the risk of no response (adjusted OR = 1.26, 95% CI: 1.14~1.41; adjusted OR = 1.13, 95% CI: 1.02~1.26). MiR-183-5p and miR-486-5p were nonlinearly and positively associated with risk of no response (P nonlinear <0.05). The stronger associations of miR-183-5p and miR-486-5p with risk of no response were observed in mothers older than 30 years and in boys (P<0.05). A random forest prediction model for no response built using the above miRNAs, demographic and HBV infection characteristics achieved superior AUC (0.931), sensitivity (0.931), and negative predictive value (0.939).Conclusion: The miR-183-5p and miR-486-5p in CBMCs are promising non-invasive biomarkers for early identification of infants at risk of hepatitis B vaccine no response, especially those born to mothers aged over 30 years and male infants. A miRNA-based model provides a novel tool to screen these high-risk infants early.

The trace element chromium (Cr) has been implicated in the risk of gestational diabetes mellitus (GDM), the underlying mechanisms remain unclear. Phospholipid remodeling is known to contribute to insulin regulation and may serve as a potential intermediate link between Cr exposure and GDM risk. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), as an important regulatory factor in phospholipid remodeling, may play a certain role in this process. For the first time, this study investigates the relationship between Cr exposure and GDM risk from the perspective of phospholipid remodeling, while integrating the genetic predisposition and epigenetic regulation of the LPCAT1 gene. A cohort comprising 107 pregnant women diagnosed with GDM and 107 matched controls without GDM was recruited. Blood samples were collected prior to delivery to perform LPCAT1 genotyping, assess DNA methylation patterns, and quantify Cr concentrations. Elevated Cr levels in maternal blood were significantly correlated with an increased risk of GDM. Furthermore, a multiplicative interaction was observed between Cr exposure and four single nucleotide polymorphisms (SNPs) within the LPCAT1 gene. Three Cr-associated DNA methylation CpG sites were identified in GDM patients. Methylation quantitative trait locus (mQTLs) analysis revealed that three SNPs (rs4371798, rs56358072, rs6554859) were significantly associated with methylation at a specific CpG site (cg22185977) within LPCAT1. These findings suggest that genetic polymorphisms in LPCAT1 may modulate individual susceptibility to Cr exposure and consequent GDM risk by influencing the methylation status of the LPCAT1 gene. This study provides novel etiological insights into the role of Cr in inducing GDM through mechanisms involving phospholipid remodeling.

The mechanism of non-/hypo-response to hepatitis B vaccine among infants born to Hepatitis B surface Antigen (HBsAg) positive mothers has not been fully clarified. Intrauterine exposure to HBsAg may alter the innate and adaptive immunity of the offspring, further complicating vaccine response. One potential factor is myeloid differentiation factor 88 (MyD88), which is a key adaptor protein linking innate and adaptive immunity and may be regulated by microRNAs (miRNAs). The study aimed to determine the impacts of intrauterine exposure to HBsAg on the immune response to hepatitis B vaccine in the offspring and the potential mechanisms. In the cohort of infants born to HBsAg positive mothers, three pairs of hepatitis B vaccine non-responsive/responsive infants were matched. And miRNA sequencing and bioinformatics were performed to identify miRNAs that are involved in regulating MyD88. Moreover, to mimic human intrauterine exposure to HBsAg, female Hepatitis B Virus-Transgenic (HBV-Tg) mice were mated with male C57BL/6J mice. After birth, pups including HBV-Tg+ and HBV-Tg− pups were administered 1 µg hepatitis B vaccine according to the 0-2-4week vaccination schedule. Among infants born to HBsAg positive mothers, microRNA-155-5p (miR-155-5p) expression was higher in non-responders than responders. miRNA sequencing and bioinformatics suggested miR-155-5p may regulate MyD88 expression in these neonates. In the animal experiment, pups with intrauterine exposure to HBsAg produced less anti-HBs after vaccination. Flow cytometry showed that both HBV-Tg− pups and HBV-Tg+ pups had less generation of CD4+ T cells, B cells, dendritic cells (DCs), and Germinal Center B (GC B) cells in comparison with wild type (WT) mice pups. Cytokine analysis demonstrated that Interleukin-6 (IL-6) and Interleukin-12 (IL-12) were expressed at lower levels in the pups with intrauterine exposure to HBsAg. Further investigation of MyD88 signaling pathway and miR-155-5p pointed that in DCs of pups with intrauterine exposure to HBsAg, there were lower expression of MyD88 and Nuclear Factor-kappa B (NF-κB), while miR-155-5p was elevated. There is a potential link between intrauterine HBsAg exposure, compromised DC generation and activation, and subsequent suboptimal vaccine response. The current data implied that intrauterine HBsAg exposure may have an inhibitory effect on the MyD88 signaling pathway in DCs, with miR-155-5p potentially negatively regulating MyD88.

Background: In East Asian populations, evidence on the association between early adulthood body mass index (BMI) and later-life chronic liver diseases is scarce, with distinct lifestyle, genetic factors, fat distribution and hepatitis B virus (HBV) infection from Western populations. This study aimed to explore this association, examine the modifying effects of midlife healthy lifestyle factors (HLFs) and hepatitis B surface antigen (HBsAg) status on this association, and evaluate the mediating effect of midlife metabolic syndrome (MetS). Methods: This prospective cohort study utilized data from the China Kadoorie Biobank (CKB), enrolling adults aged 35–70 years free of baseline cancer or liver disease. A total of 387,541 participants from ten Chinese regions were included in the analysis. Primary outcomes were morbidity of chronic liver disease (CLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD), which were obtained mainly through local disease and death registries and the national health insurance (HI) system. Weight at age 25, midlife lifestyle and HBsAg status were obtained from the CKB baseline survey. Cox proportional hazards models were applied to estimate the association between early adulthood BMI and later-life liver-related outcomes. Interaction analysis was performed to examine the modifying effects of midlife HLF and HBsAg status. The Bootstrap method was used to verify the mediation effect of MetS in the association under investigation. Findings: The baseline survey was conducted from 2004 to 2008. During a median follow-up of 12·1 years 5,983 (1·5%) incident CLD cases were documented. After adjustment for covariates, elevated early-adulthood BMI was associated with increased later-life CLD risk in a monotonic dose-response manner (P for trend <0·001). Compared with the reference group (BMI 20·5-22·4 kg/m²), the hazard ratio (HR) for later-life CLD was 1·03 (95%CI 0·96-1·11) for BMI in 22·5-23·9 kg/m², 1·19 (1·09-1·29) for 24·0-25·9 kg/m², 1·35 (1·20-1·53) for 26·0-27·9 kg/m², 1·69 (1·40-2·04) for 28·0-29·9 kg/m², and 1·66 (1·24-2·23) for ≥30·0 kg/m². No significant interaction was observed between midlife HLF and early adulthood BMI for later-life CLD risk (P > 0·05), whereas HBsAg status exhibited a significant interaction with early adulthood BMI (P = 0·008), and in the HBsAg-negative group, later-life CLD risk was positively associated with early adulthood BMI. MetS-mediated effect was strongest for MASLD, the proportion mediated increased from 20·71% to 46·74% with rising BMI (all P < 0·001). Interpretation: This study confirms that higher BMI in early adulthood significantly increases the risk of later-life chronic liver diseases among Chinese adults, particularly in HBsAg-negative adults, regardless of subsequent lifestyle changes. These findings highlight the urgency for public health strategies to prevent overweight in young adulthood and to optimize the management of HBV infection.

This study aims to delineate the levels of Cd exposure in maternal blood, placenta, and cord blood, and to explore the association between Cd levels and the risk of preeclampsia (PE), as well as its potential impact on fetal growth among affected individuals. A case-control study was performed at the First Hospital of Shanxi Medical University, involving 373 pregnant women diagnosed with PE and 485 controls. Cd was measured in maternal blood, placenta, and cord blood using ICP-MS. The association between Cd and birth weight z-score was analyzed by multivariate linear regression. Logistic regression analysis was used to investigate the relationships between Cd and the risk of PE, and Cd and the risk of fetal growth. The concentration of Cd in the placenta was higher than that in maternal blood and cord blood. The highest tertile of placental Cd was identified as a risk factor for PE (OR = 2.704, 95

BACKGROUND:People infected with human immunodeficiency virus (HIV) are more likely to be infected with hepatitis B virus (HBV), which is a significant public health concern. It is essential to provide protection through the hepatitis B vaccine and to stimulate higher and more sustained levels of anti-HBs antibodies to ensure long-term immunity. We aimed to enhance the duration of immunogenicity by implementing high-dose and multiple-schedule hepatitis B vaccination in adults infected with HIV. METHODS:This open-label, parallel-group, randomised controlled trial (RCT) was conducted between May 2020 and January 2021 at the Second Hospital of Yuncheng. Patients were randomised to receive 3 or 4 doses of 20 μg or 60 μg of hepatitis B vaccine. The follow-up period was extended to 2022 to evaluate the duration of immunogenicity. RESULTS:The geometric mean concentration (GMC) and response rates of hepatitis B surface antibody (anti-HBs) at month 18 were 200.40 mIU/ml and 66.67 % (58/87) in the IM20 × 3 group, 382.20 mIU/ml and 75.58 % (65/86) in the IM20 × 4 group, 628.50 mIU/ml and 83.13 % (69/83) in the IM60 × 4 group, which were significantly different between the IM20 × 3 and IM60 × 4 groups (P < 0.017). In multivariate analysis, gender and vaccination regimens affected the duration of immunogenicity at month 18. Regarding the multiplicative scale, the interaction effect was significant between the male and the IM60 × 4 group after adjusting for confounders. CONCLUSION:In the one-year follow-up (month 18) of adults infected with HIV, four triple doses regimen of hepatitis B vaccine improved the duration of immunogenicity in male patients.

Introduction:Folic acid has been associated with fetal development, especially in fetal immunity. Therefore, limited evidence regarding the effects of different folic acid supplementation of hepatitis B surface antigen (HBsAg) positive mothers in innate immunity in offspring. Herein, this study aimed to explore the association between folic acid supplementation and the innate immunity of neonates and the immunological efficacy of hepatitis B vaccine (HepB), which may provide insights that could inform pre-pregnancy health management in HBsAg-positive mothers. Materials and methods:It is an ambispective cohort study with 293 pairs of HBsAg-positive mothers-offspring in Taiyuan, Shanxi Province, China. Mothers were classified into three groups according to the time of starting folic acid supplementation, non-supplementation group, pre-pregnancy group and post-pregnancy supplementation group. Immunological indexes such as immune cells proportion and innate immune mediators in cord blood and anti-HBs in infants were measured. Differences in immunological indexes were analyzed by One-Way ANOVA test. Univariate and multivariate analyses were performed for factors associated with abnormal immunological indexes and potential confounders were adjusted. Results:The preconception folic acid group showed a significantly higher expression levels of STING (P = 0.005) and pNF-κB (P = 0.010) in cord blood along with higher anti-HBs titres (P = 0.006), when compared to both non-supplementation group and post-pregnancy supplementation group. Higher anti-HBs levels indicate a stronger immune response to HepB and may enhance protection against HBV infection during early life. Infants in the high pNF-κB expression group exhibited a significantly elevated seropositive rate of HepB compared to those in the low pNF-κB expression group (P = 0.037). There were no mediation effects and no moderation effects in this study, potentially due to the direct influence of folic acid supplementation on immune responses or the limited sample size. Discussion:In conclusion, our findings demonstrate that preconception folic acid supplementation may enhance HepB vaccine responsiveness in infants of HBsAg-positive mothers. Meanwhile, high pNF-κB expression in cord blood can increase seropositive rates in infants. This discovery has significant public health implications, as it may provide a simple and accessible intervention to improve vaccination outcomes and reduce HBV transmission in endemic regions.

This study investigates the role of the STING signaling pathway in enhancing dendritic cells (DCs) maturation and activation in response to the hepatitis B vaccine. By analyzing the GSE52894 dataset, we compared differentially expressed genes between mature dendritic cells (mDCs) and immature dendritic cells (iDCs). In vitro, iDCs were treated with the STING agonist 2'3'-cGAMP, either alone or in combination with lipopolysaccharide (LPS) or the hepatitis B vaccine, to assess the expression of costimulatory molecules and key signaling molecules in the STING pathway, including STING, pNF-κBp65, and pIRF3. The results indicated that mDCs expressed significantly higher levels of STING mRNA compared to iDCs (P < 0.01). Treatment with 2'3'-cGAMP increased STING expression and activated downstream signaling molecules pNF-κBp65 and pIRF3. Co-treatment with 2'3'-cGAMP and LPS upregulated costimulatory molecules (CD80, CD86, HLA-DR, CD11c) more effectively than LPS alone (P < 0.05). Co-treatment with 2'3'-cGAMP and the hepatitis B vaccine resulted in significantly higher expression of costimulatory molecules compared to vaccine-only treatment. Furthermore, co-treatment with 2'3'-cGAMP and the hepatitis B vaccine enhanced STING, pNF-κBp65, and pIRF3 expression relative to vaccine alone. Mixed lymphocyte reaction assays demonstrated that the 2'3'-cGAMP and hepatitis B vaccine co-treatment group had a significantly stronger effect on the proliferation of CD4+T cells compared to the vaccine-only treatment group. In conclusion, 2'3'-cGAMP enhances DCs maturation and promotes CD4+T cells proliferation in response to the hepatitis B vaccine by activating the STING/IRF3 and STING/NF-κB pathways, highlighting its potential as an adjuvant to improve vaccine efficacy.

OBJECTIVE:To investigate the relationship between DNA methylation of cord blood apoptosis genes and low birth weight (LBW). METHODS:A case-control study was conducted on 50 pairs of LBW neonates and normal birth weight. Genome-wide methylation assay was performed using Illumina Human Methylation EPIC microarray to analyze the methylation sites of apoptosis-related genes BCL-2, CASP3, and CASP8. The mRNA level of apoptosis gene was verified by RT-qPCR. RESULTS:Three CpG sites of BCL-2 and three CpG sites of CASP3 were different between the LBW and NBW groups. Logistic regression showed that higher methylation of BCL-2 CpG sites cg12459502 (OR = 1.208, 95% CI:1.029, 1.418) and cg25059899 (OR = 1.193, 95% CI:1.019, 1.395) increased LBW risk, while cg22152050 was protective (OR = 0.589, 95% CI:0.424, 0.820). Stratified analysis confirmed this. Maternal pre-pregnancy BMI positively correlated with BCL-2 methylation (cg12459502, cg25059899) (b = 0.431, 95% CI: 0.027, 0.835; b = 0.494, 95% CI: 0.141, 0.848), while excessive pregnancy weight gain negatively correlated with cg12459502 methylation (b = -0.269, 95% CI: -0.525, -0.013). The results showed that the mRNA level of BCL-2 in NBW group was significantly higher than that in LBW group (P-value < 0.0001). CONCLUSION:The DNA methylation levels of BCL-2 and CASP3 genes are associated with fetal growth and development. Additionally, maternal pre-pregnancy BMI and weight gain during pregnancy were found to correlate with BCL-2 methylation, indicating potential epigenetic mechanisms influencing fetal growth.

To comprehensively evaluate the epidemiological burden, temporal trends, socio-demographic inequalities, and long-term forecasting of fall-related injuries in older adults (aged ≥ 55 years) through systematic analysis of the Global Burden of Disease (GBD) 2021 dataset. We extracted data on fall-related incidence, prevalence, deaths, and disability-adjusted life years (DALYs) for adults aged ≥ 55 from the GBD database (1990–2021). Temporal trends were assessed using estimated annual percentage changes (EAPCs) and joinpoint regression. Age-period-cohort modeling was applied to disentangle the effects of age, time period, and birth cohort. Socioeconomic inequalities were evaluated using the slope index of inequality and concentration index. Future projections to 2046 were generated via Bayesian Age-Period-Cohort analysis. Between 1990 and 2021, the absolute number of fall-related incidence, deaths, and DALYs among older adults doubled globally. While age-standardized rates remained relatively stable, distinct patterns emerged across Socio-demographic Index (SDI) regions: high SDI regions had the highest incidence and prevalence, whereas low SDI regions experienced higher mortality. Joinpoint regression identified sex-specific acceleration phases, notably 2005–2021 for incidence (APC = 3.747), with women demonstrating higher ASIR but men showing elevated ASPR/ASDR. Significant socioeconomic inequalities were observed and have widened over time. Projections indicate a continued increase in the absolute burden of falls through 2046, despite stable or declining age-standardized rates. Falls represent a major and growing public health challenge among older adults worldwide, with pronounced disparities across sex and socioeconomic levels. There is an urgent need for targeted prevention strategies and enhanced resource allocation—particularly in low SDI settings—to reduce the health impact of falls in aging populations.

CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov (NCT03962816).https://clinicaltrials.gov/ct2/show/NCT03962816.

Introduction:Human immunodeficiency virus (HIV), syphilis, and hepatitis B virus (HBV) infection pose a major global public health challenge. However, high-quality integrated data on the burden of these diseases among women of childbearing age (WCBA) and children remain limited. This study aims to provide a comprehensive global assessment of HIV, syphilis, and HBV infection among WCBA and children under five and to explore their potential relationships. Methods:The Global Burden of Disease Study 2021 provided data on the global prevalence of WCBA and incidence of HIV, syphilis, and HBV infection in children under five years old from 1990 to 2021. Temporal trends were analyzed using annual average percentage change (AAPC) and joinpoint regression. A Bayesian age-period-cohort model was used to forecast the disease burden from 2022 to 2030. Results:In 2021, the age-standardized prevalence (ASPR) of HIV infection among WCBA was 830.87 per 100,000, while the age-standardized incidence (ASIR) of HIV among children under five was 15.39 per 100,000. From 1990 to 2021, the ASPR of HIV in WCBA demonstrated sustained growth, whereas the ASIR in children exhibited a rise-then-fall pattern. For syphilis, the 2021 ASPR among WCBA was 1057.32 per 100,000, and the ASIR in children was 58.36 per 100,000; both metrics followed a declining-then-rising trend, returning to 1990 levels by 2021. Both the ASPR of HBV infection among WCBA and the ASIR among children under five declined significantly from 1990 to 2021, with average annual percentage changes of -1.25% and -4.14%, respectively. Generally, ASPR and ASIR decreased as the sociodemographic index (SDI) increased. Regions with lower SDI experienced a disproportionately higher burden of HIV, syphilis, and HBV infections. Conclusion:In 2021, the global disease burden of HIV, syphilis, and HBV infection remained high among WCBA and children under five, with significant regional and demographic disparities. These findings indicate a persistent public health challenge, necessitating continued global efforts to mitigate the burden through addressing socioeconomic inequalities, strengthening health education, and expanding healthcare access.

Environmental metal exposure is a key risk factor for gestational diabetes mellitus (GDM), but the mechanisms remain unclear. The traditional view holds that excessive accumulation of metals directly damages the islets to induce GDM. Recent studies suggest that supplementing with trace elements can alleviate insulin resistance by reducing endoplasmic reticulum stress, indicating that endoplasmic reticulum stress might have a comparable impact in metal-induced GDM. Selenoprotein S (SEPS1), a key regulator of endoplasmic reticulum function, may play a role. This study aims to investigate the interaction between the genetic predisposition of the SEPS1 gene and exposure to metals on GDM from the perspective of endoplasmic reticulum stress. A total of 278 pregnant women with GDM and 278 matched pregnant women without GDM were recruited. Maternal blood samples were collected before delivery to genotype the SEPS1 gene and measure metal levels. We found that rs28533324 and rs894317 were associated with the risk of GDM. The level of chromium (Cr) Q3 in maternal blood increased the risk of GDM, and the level of nickel (Ni) Q4 decreased the risk of GDM. Furthermore, the Q3 and Q4 Cr exhibit a multiplicative interaction with rs894317 in both the codominant and dominant models, and a multiplicative interaction between the Cr Q3 and rs894317 is also observed in the allele model. We found a novel link between SEPS1 gene variation and GDM, with these associations potentially being modified by Cr exposure. Our findings provide new etiological insights into GDM induced by Cr through endoplasmic reticulum stress.

Liver cancer due to hepatitis B (LCHB) presents a major public health challenge, particularly in younger populations. To date, comprehensive analyses of the global burden and changing trends of LCHB in young adults aged 15–49 years are understudied. We collected prevalence, mortality, and disability-adjusted life years (DALYs) between 1990 and 2021 from the Global Burden of Disease (GBD) Study 2021. Percentage change and estimated annual percentage change (EAPC) were calculated to quantify temporal trends. The future burden to 2030 was projected using the Bayesian age-period-cohort (BAPC) model. From 1990 to 2021, the global prevalence, mortality, and DALYs cases of LCHB in young adults increased by 49.72

BACKGROUND:Trace element Cu is associated with the risk of small for gestational age infants, but its underlying mechanism is still unclear. This study aims to explore the possible mechanism of Cu induced SGA from the perspective of DNA methylation. METHODS:We performed epigenome-wide DNA methylation analysis of umbilical cord blood from small for gestational age infants (SGA, n = 35) and appropriate for gestational age infants (AGA, n = 61) at birth to explore SGA related epigenome-wide DNA methylation sites. Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) was used to detect their umbilical cord blood Cu levels. Multiple linear regression models were used to explore the effect of Cu on SGA-related DNA methylation sites, and mediation analysis was further applied to explore the potential mediating factors of DNA methylation. The false discovery rate（FDR）was used for multiple comparisons. RESULTS:Compared with AGA (452 ng/mL), SGA infants (532 ng/mL) had higher umbilical cord blood Cu concentration (P < 0.05). Seven Cu-related CpG sites were identified from epigenome-wide DNA methylation association analysis with SGA. Among them, a significant mediation effect of FLT3（cg10763141） methylation level in the association between high exposure level of Cu and SGA (P = 0.024). The mediation analysis showed a mediation proportion of 44.7 %. CONCLUSIONS:Consistent with previous findings, we found that Cu was associated with the risk of SGA, and seven differentially methylated sites significantly associated with Cu were observed in the epigenome wide DNA methylation association study of SGA. FLT3（cg10763141）mediates the correlation between Cu and SGA. Cu may increase the risk of SGA by altering DNA methylation in certain genes (particularly FLT3). Our study provides new clues for the mechanism of SGA.

The issue of breast cancer in young women (BCYW) has gained increasing attention over the past few decades. However, a notable gap exists in the literature concerning the comparison of the disease burden of BCYW with that of other age groups. This study presents a comprehensive analysis of the disparities in global, regional, and national burden between BCYW and their middle-aged and elderly counterparts. The breast cancer data in this study were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). The age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and age-standardized disability-adjusted life years rate (ASDR), and the Average Annual Percent Change (AAPC) were employed to assess the disease burden of BCYW. The Bayesian Age-Period-Cohort model was used to forecast disease burden from 2022 to 2030. The AAPC of ASIR of BCYW from 1990 to 2021 was 0.91 (95

Prenatal exposure to Benzo[a]pyrene (BaP) has been shown to increase the risk of adverse birth outcomes, potentially through disruption of maternal metabolic homeostasis. However, the underlying pathways and mechanisms remain unclear. To address this knowledge gap, we employed a multi-omics approach combining experimental and epidemiological investigations. In the mouse model, untargeted metabolomics profiling revealed niacinamide (NAM) metabolism as the most significantly altered pathway in both maternal serum and placenta following BaP exposure. Mechanistically, BaP exposure reduced nicotinamide adenine dinucleotide (NAD+) synthesis while increasing its catabolism through activation of poly (ADP-ribose) polymerase 1 (PARP1) in placental tissue. Subsequent transcriptomic analysis showed that BaP-induced NAD+ depletion led to sirtuin 1 (SIRT1) suppression and consequent exacerbation of the NF-κB-mediated inflammatory response. These experimental findings were substantiated in human populations through targeted metabolomic analysis of a Chinese birth cohort, where significant NAM metabolic disturbances were observed in women with high BaP exposure experiencing preterm delivery. Our study provides novel mechanistic evidence that BaP-induced dysregulation of NAM metabolism mediates adverse birth outcomes through NAD+ deficiency and subsequent inflammatory response. These findings not only identify potential therapeutic targets but also highlight the urgent need for evidence-based environmental policy interventions and nutritional supplementation strategies to protect maternal-fetal health in high-risk populations.

BACKGROUND:Patients receiving hemodialysis represent a high-risk group for hepatitis B virus (HBV) infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of hepatitis B surface antibodies (anti -HBs). Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedules in patients receiving hemodialysis. METHODS:We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 patients receiving hemodialysis were enrolled. All participants were randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 μg) at 0, 1, and 6 months (IM20 × 3 group), 4 standard doses at 0, 1, 2, and 6 months (IM20 × 4 group), or 4 triple doses (60 μg) at 0, 1, 2, and 6 months (IM60 × 4 group). RESULTS:The vaccine-elicited antibody response peaked at month 7. The follow-up from month 7 to 30 revealed that response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20 × 3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20 × 4 group, and from 95.4% (145/152) to 57.3% (55/96) in IM60 × 4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibodies were 21.0 months in IM20 × 3 group, 25.7 months in IM20 × 4 group (vs IM20 × 3 group, P = .056), and 29.2 months in IM60 × 4 group (vs IM20 × 3 group, P = .034). All the adverse reactions were mild. CONCLUSIONS:The triple-strength 4-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in patients receiving hemodialysis.Clinical Trials Registration. NCT03962881.