Can COVID-19 Increase Platelet in Adult Immune Thrombocytopenia During the TPO-RA Administration? A Real-World Observational Study.

Introduction: COVID-19 infection has brought new challenges to the treatment of adult patients with immune thrombocytopenia (ITP). In adult ITP patients, there have been no relevant reports exploring the incidence, clinical characteristics, and risk factors of platelet elevation after COVID-19 infection. Materials and Methods: A total of 66 patients with previously diagnosed ITP from December 2022 to February 2023 in a single-center were collected and analyzed for this real-world clinical retrospective observational study. Results: In the platelet count increased group (n = 19), 13 patients (68.4%) were using thrombopoietin receptor agonists (TPO-RA) treatment at the time of COVID-19 infection; the median platelet count was 52 (2-207) ×109/L at the last visit before infection and 108 (19-453) ×109/L at the first visit after infection. In the platelet count stable group (n = 19) and platelet count decreased group (n = 28), 9 (47.4%) and 8 (28.6%) patients were using TPO-RA at the time of infection, respectively. ITP patients treated with TPO-RA had a significantly higher risk of increased platelet count than those not treated with TPO-RA at the time of infection (platelet count increased group vs platelet count decreased group: OR: 5.745, p = 0.009; platelet count increased group vs the non-increased group: OR: 3.616, p = 0.031). In the platelet count increased group, the median platelet count at 6 months post-infection was 67 (14-235) × 109/L, which was significantly higher than the platelet level at the last visit before infection (p = 0.040). Conclusion: This study showed that some adult ITP patients had an increase in platelet count after COVID-19 infection, and this phenomenon was strongly associated with the use of TPO-RA at the time of infection. Although no thrombotic events were observed in this study, it reminds clinicians that they should be alert to the possibility of thrombotic events in the long-term management of adult ITP patients during the COVID-19 pandemic.

[Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on Angâ ¡-induced cardiomyocyte hypertrophy].

This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 µmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.

The impact of maternal anxiety during pregnancy on children's eczema and allergic rhinitis: The Ma'anshan birth cohort study.

OBJECTIVE: The objective of this study was to investigate the associations between maternal exposure to anxiety during pregnancy and the susceptibility of offspring to eczema and allergic rhinitis and the possibility of sensitivity periods and cumulative effects. METHODS: The study's sample consisted of 3160 mother-child pairs from the Ma'anshan Birth Cohort Study. Maternal anxiety was repeatedly measured in the 1st, 2nd, and 3rd trimesters of pregnancy using the Chinese version of the Pregnancy-Related Anxiety Scale. Information regarding children's eczema and allergic rhinitis diagnoses was collected through parental reports at 12, 24, 36 and 48 months of age. Binary logistic regression models were used for statistical analysis and corrected for multiple comparisons using the false discovery rate (FDR) method. RESULTS: Children whose mothers experienced anxiety throughout pregnancy had the highest odds of developing total eczema (aOR 1.45, 95% CI 1.02-2.07) and total allergic rhinitis (aOR 1.67, 95% CI 1.17-2.37) between the ages of 6 and 48 months. The higher the trajectory of the maternal anxiety scores throughout pregnancy, the higher the odds of total eczema (aOR 1.65, 95% CI 1.14-2.40) and allergic rhinitis (aOR 1.84, 95% CI 1.28-2.66) in their offspring. The association between maternal anxiety and children's eczema was mainly concentrated in the first 24 months, whereas the association with allergic rhinitis was mainly concentrated in the 36-48 months. CONCLUSION: Maternal anxiety during any trimester of pregnancy, especially with a consistently high trajectory of anxiety scores, was associated with higher odds of children's eczema and allergic rhinitis.

Association between maternal fasting glucose levels throughout pregnancy and preschoolers' refractive errors.

PURPOSE: We aimed to investigate the association between maternal fasting plasma glucose (FPG) trajectories during pregnancy and children's refractive errors at 6 years old. DESIGN: Based on the Ma'anshan Birth Cohort (MABC) in China, a total of 1987 mother-child pairs were included in this study. METHODS: Using the group-based trajectory model, trajectory fitting was performed on fasting blood glucose levels during the first, second, and third trimesters of pregnancy. Children's vision was measured at 6 years of age using the standard logarithmic visual acuity E-chart and cycloplegic refraction examination. Logistic regression models and multi-informant generalized estimating equations were used to analyze the association between maternal blood glucose level and 6-year-old children's visual acuity. RESULTS: Children born of mothers with high level FPG trajectory had a higher risk of developing refractive error [OR=1.46 (95% CI 1.08 1.97)], hypermetropia [OR=1.64 (95% CI 1.09, 2.46)] and astigmatism [OR=1.60 (95% CI 1.06, 2.41)] at age six compared to those with low level trajectory. Maternal blood glucose level in the first [ß=-0.012 (95% CI -0.024, -0.001)] and the second [ß=-0.016 (95% CI -0.025, -0.006)] trimesters was associated with 6 year children's distance vision value. CONCLUSIONS: High level of fasting plasma glucose trajectories during pregnancy has been observed to be associated with 6-year-old children's refractive error, hypermetropia and astigmatism. The first and the second trimesters may be critical periods for the effects of maternal blood glucose on children's vision. The long-term effect of maternal glucose metabolism on children's visual development deserves further study.

Artificial intelligence-based MRI radiomics and radiogenomics in glioma.

The specific genetic subtypes that gliomas exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of gliomas pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). Radiomics and radiogenomics present a potential to precisely diagnose and predict survival and treatment responses, via morphological, textural, and functional features derived from MRI data, as well as genomic data. In spite of their advantages, it is still lacking standardized processes of feature extraction and analysis methodology among different research groups, which have made external validations infeasible. Radiomics and radiogenomics can be used to better understand the genomic basis of gliomas, such as tumor spatial heterogeneity, treatment response, molecular classifications and tumor microenvironment immune infiltration. These novel techniques have also been used to predict histological features, grade or even overall survival in gliomas. In this review, workflows of radiomics and radiogenomics are elucidated, with recent research on machine learning or artificial intelligence in glioma.

Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status.

Organophosphate esters (OPEs) and phthalate acid esters (PAEs) are prevalent endocrine-disrupting chemicals (EDCs). Humans are often exposed to OPEs and PAEs simultaneously through multiple routes. Given that fetal stage is a critical period for neurodevelopment, it is necessary to know whether gestational co-exposure to OPEs and PAEs affects fetal neurodevelopment. However, accessible epidemiological studies are limited. The present study included 2, 120 pregnant women from the Ma'anshan Birth Cohort (MABC) study. The concentrations of tris (2-chloroethyl) phosphate (TCEP), 6 OPE metabolites and 7 PAE metabolites were measured in the first, second and third trimester using ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Cognitive development of preschooler was assessed based on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) of the Chinese version. Generalized estimating equations (GEEs), restricted cubic spline (RCS) and generalized additive models (GAMs) were employed to explore the associations between individual OPE exposure and preschooler cognitive development. The quantile-based g-computation (QGC) method was used to estimate the joint effect of PAEs and OPEs exposure on cognitive development. GEEs revealed significant adverse associations between diphenyl phosphate (DPHP) (ß: -0.58, 95% CI: -1.14, -0.01), bis (2-butoxyethyl) phosphate(BBOEP) (ß: -0.44, 95% CI: -0.85, -0.02), bis(1-chloro-2-propyl) phosphate (BCIPP) (ß: -0.81, 95%CI: -1.43, -0.20) and full-scale intelligence quotient (FSIQ) in the first trimester; additionally, TCEP and bis(2-ethylhexyl) phosphate (BEHP) in the second trimester, as well as DPHP in the third trimester, were negatively associated with cognitive development. Through the QGC analyses, mixture exposure in the first trimester was negatively associated with FSIQ scores (ß: -1.70, 95% CI: -3.06, -0.34), mono-butyl phthalate (MBP), BCIPP, and DPHP might be the dominant contributors after controlling for other OPEs and PAEs congeners. Additionally, the effect of OPEs and PAEs mixture on cognitive development might be driven by vitamin D deficiency.

Impact of Gestational Exposure to Individual and Combined Per- and Polyfluoroalkyl Substances on a Placental Structure and Efficiency: Findings from the Ma'anshan Birth Cohort.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.

Prenatal antibiotics exposure and preschoolers' internalizing and externalizing problems: A biomonitoring-based prospective birth cohort study.

BACKGROUND: Biomonitoring-based epidemiological studies on prenatal antibiotic exposure and behavioral problems in preschoolers are lacking. The present study aimed to investigate the relationship between prenatal antibiotic exposure and internalizing and externalizing problems in preschoolers. METHODS: Data from 2449 mother-child pairs were analyzed. Urine samples were repeatedly collected across three trimesters, and 43 antibiotics and 2 metabolites were measured, including preferred as veterinary antibiotics (PVAs), VAs, preferred as human antibiotics and human antibiotics. Preschoolers' internalizing and externalizing problems were evaluated by the Achenbach Child Behavior Checklist. Poisson regression models with generalized estimating equations were used to estimate risk ratios (RRs) and 95 % confidence intervals (CIs) for preschoolers' internalizing, externalizing and total problems across tertiles of antibiotic concentrations during three periods of pregnancy, and performed several subgroup analyses. RESULTS: First-trimester urinary oxytetracycline (RR = 1.69, 95%CI: 1.20, 2.39, P-FDR = 0.011), tetracycline (RR = 1.91, 95%CI: 1.36, 2.68, P-FDR < 0.001), doxycycline (RR = 1.66, 95%CI: 1.28, 2.17, P-FDR < 0.001) and PVAs (RR = 1.79, 95%CI: 1.29, 2.48, P-FDR < 0.001) concentrations in the highest tertile were related to an elevated risk of internalizing problems compared with concentrations in the lowest tertile. First-trimester urinary doxycycline concentrations in the third tertile were also associated with an increased risk of externalizing problems compared with the first tertile (RR = 2.00, 95%CI: 1.28, 3.15, P-FDR = 0.042). Compared with concentrations in the lowest tertile, first-trimester urinary doxycycline (RR = 1.63, 95%CI: 1.19, 2.22, P-FDR = 0.028) and PVAs (RR = 1.67, 95%CI: 1.14, 2.43, P-FDR = 0.047) concentrations in the middle tertile were related to an increased risk of total problems. Furthermore, the type of main caregiver and children's outdoor activities time modified the relationships between specific prenatal antibiotic exposure and preschoolers' behavioral problems. CONCLUSIONS: Exposure to specific antibiotics during the first trimester may be related to an increased risk of internalizing and externalizing problems in preschoolers.

Ultrafast and selective capture of 99TcO4-/ReO4- from wastewater by hyper-branched quaternary ammonium group-functionalized resin.

99Tc primarily exists high mobility in the natural aqueous environment due to its extremely high solubility and non-complexing features, which can easily cause radioactive pollution. We herein report a general strategy for constructing a novel resin (SiPAN-PEI) with multiple positive charges nitrogen, exhibiting ultrafast adsorption kinetics (< 3 min), superior adsorption capacities (463.96 mg g-1), and excellent selectivity in the presence of excess competitive anions, which exceed those of most commercial resins. Moreover, based on impressive structure stability in extreme conditions, SiPAN-PEI can still maintain superior adsorption abilities after suffering irradiation, calcination, and immersion in strong acid. In addition, the separation performance kept excellently after five loading-washing-eluting cycles and the total adsorption ratio can still reach 97 %. Outstandingly, SiPAN-PEI can remove most of ReO4- from simulated nuclear wastewater through a sequential injection automatic separation system and can reduce the concentration of ReO4- to the maximum concentration standard set by the World Health Organization (WHO) in a short time. Leveraging density functional theory calculations and other characteristics clearly elucidated adsorption mechanism of anion-exchange between Cl- and TcO4-/ReO4-. In terms of superior adsorption property, SiPAN-PEI is demonstrated to be a pretty candidate for 99Tc elimination from wastewater.

Selinexor Synergistically Promotes the Antileukemia Activity of Venetoclax in Acute Myeloid Leukemia by Inhibiting Glycolytic Function and Downregulating the Expression of DNA Replication Genes.

Introduction: The BCL-2 inhibitor venetoclax has been widely used in the treatment of acute myeloid leukemia (AML); however, AML patients treated with venetoclax gradually develop resistance. The exportin-1 (XPO1) inhibitor selinexor can synergistically promote the antileukemia activity of venetoclax, but the mechanism remains unclear. Methods and Results: Annexin V/7-aminoactinomycin D assays were used to examine the effects of a combination of venetoclax and selinexor (VEN+SEL) on AML cell lines and primary AML cells. RNA sequencing and oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) determinations by a Seahorse XF analyzer were employed to investigate the molecular mechanism of the toxicity of the VEN+SEL combination to AML cells. The cytotoxicity of NK cell combined with VEN+SEL combination was assessed in vitro using flow cytometry. VEN+SEL enhanced the apoptosis of AML cells (KG-1A and THP-1) and primary AML samples in vitro. The ECAR and OCR results demonstrated that the VEN+SEL combination significantly inhibited glycolytic function. RNA sequencing of THP-1 cells demonstrated that DNA replication-related genes were downregulated after treatment with the VEN+SEL combination. Conclusion: This study indicated that selinexor can synergistically enhance the antileukemia activity of venetoclax in AML cells in vitro by inhibiting glycolytic function and downregulating DNA replication-related genes. Based on our experimental data, combining selinexor with venetoclax is an appropriate advanced treatment option for AML patients.

Placental inflammatory cytokines mRNA expression and preschool children's cognitive performance: a birth cohort study in China.

BACKGROUND: The immunologic milieu at the maternal-fetal interface has profound effects on propelling the development of the fetal brain. However, accessible epidemiological studies concerning the association between placental inflammatory cytokines and the intellectual development of offspring in humans are limited. Therefore, we explored the possible link between mRNA expression of inflammatory cytokines in placenta and preschoolers' cognitive performance. METHODS: Study subjects were obtained from the Ma'anshan birth cohort (MABC). Placental samples were collected after delivery, and real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the mRNA expression levels of IL-8, IL-1ß, IL-6, TNF-α, CRP, IFN-γ, IL-10, and IL-4. Children's intellectual development was assessed at preschool age by using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Multiple linear regression and restricted cubic spline models were used for statistical analysis. RESULTS: A total of 1665 pairs of mother and child were included in the analysis. After adjusting for confounders and after correction for multiple comparisons, we observed that mRNA expression of IL-8 (ß = - 0.53; 95% CI, - 0.92 to - 0.15), IL-6 (ß = - 0.58; 95% CI, - 0.97 to - 0.19), TNF-α (ß = - 0.37; 95% CI, - 0.71 to - 0.02), and IFN-γ (ß = - 0.31; 95% CI, - 0.61 to - 0.03) in the placenta was negatively associated with preschoolers' full scale intelligence quotient (FSIQ). Both higher IL-8 and IL-6 were associated with lower children's low fluid reasoning index (FRI), and higher IFN-γ was associated with lower children's working memory index (WMI). After further adjusting for confounders and children's age at cognitive testing, the integrated index of six pro-inflammatory cytokines (index 2) was found to be significantly and negatively correlated with both the FSIQ and each sub-dimension (verbal comprehension index (VCI), visual spatial index (VSI), FRI, WMI, processing speed index (PSI)). Sex-stratified analyses showed that the association of IL-8, IFN-γ, and index 2 with children's cognitive development was mainly concentrated in boys. CONCLUSIONS: Evidence of an association between low cognitive performance and high expression of placental inflammatory cytokines (IL-8, IL-6, TNF-α, and IFN-γ) was found, highlighting the potential importance of intrauterine placental immune status in dissecting offspring cognitive development.

Early sleep duration trajectories and children's cognitive development: a prospective cohort study.

We aimed to investigate the association between sleep duration trajectories and cognitive performance in preschool-aged Chinese children. We included 2131 children from the Ma'anshan birth cohort (MABC) study. Sleep duration trajectories from 6 to 48 months of age were determined using the group-based trajectory modeling (GBTM). Children's intellectual development was assessed using the Wechsler Preschool and Primary Scale of Intelligence. Compared to those with a medium total sleep duration trajectory, children with a short total sleep duration trajectory had poorer cognitive performance on the Visual Spatial Index (VSI) (ß = -3.65; 95% CI = -6.77 to -0.53), which was associated with an increased risk of a low full-scale intelligence quotient (FSIQ) (OR = 1.60; 95% CI = 1.02 to 2.51). The short total sleep duration trajectory was associated with a low VSI compared with both the medium total sleep duration trajectory and the long total sleep duration trajectory. Compared to children with normal nighttime sleep duration and normal daytime sleep duration trajectories, children with short nighttime sleep and long daytime sleep duration trajectories, normal nighttime sleep and long daytime sleep duration trajectories, and short nighttime sleep and normal daytime sleep duration trajectories all had lower cognitive performance. The restricted cubic spline (RCS) also showed that children with and appropriate total sleep duration, an adequate nighttime sleep duration, and a moderate daytime sleep duration had higher FSIQ. CONCLUSIONS: The results of this study emphasize that a medium total sleep duration, adequate sleep at nighttime, and appropriate sleep in the daytime appear to be more beneficial for children's cognitive development. WHAT IS KNOWN: • Sleep duration in infancy is strongly associated with neurocognitive development. WHAT IS NEW: • Medium and long total sleep duration trajectories are beneficial for children's cognitive performance compared to the short total sleep duration trajectory. • A medium total sleep duration, adequate sleep at nighttime and appropriate sleep in the daytime appear to be more beneficial for children's cognitive development.

Microbial community structure and functional prediction in five full-scale industrial park wastewater treatment plants.

The development of industrial parks has become an important global trend contributing significantly to economic and industrial growth. However, this growth comes at a cost, as the treatment of multisource industrial wastewater generated in these parks can be difficult owing to its complex composition. Microorganisms play a critical role in pollutant removal during industrial park wastewater treatment. Therefore, our study focused on the microbial communities in five full-scale industrial park wastewater treatment plants (WWTPs) with similar treatment processes and capacities. The results showed that denitrifying bacteria were dominant in almost every process section of all the plants, with heterotrophic denitrification being the main pathway. Moreover, autotrophic sulfur denitrification and methane oxidation denitrification may contribute to total nitrogen (TN) removal. In plants where the influent had low levels of COD and TN, dominant bacteria included oligotrophic microorganisms like Prosthecobacter (2.88 % ~ 10.02 %) and hgcI_clade (2.05 % ~ 9.49 %). Heavy metal metabolizing microorganisms, such as Norank_f__PHOS-HE36 (3.96 % ~ 5.36 %) and Sediminibacterium (1.86 % ~ 5.34 %), were prevalent in oxidation ditch and secondary settling tanks in certain plants. Functional Annotation of Prokaryotic Taxa (FAPROTAX) revealed that microbial communities in the regulation and hydrolysis tanks exhibited higher potential activity in the nitrogen (N) and sulfur (S) cycles than those in the oxidation ditch. Sulfate/sulfite reduction was common in most plants, whereas the potential occurrence of sulfide compounds and thiosulfate oxidation tended to be higher in plants with a relatively high sulfate concentration and low COD content in their influent. Our study provides a new understanding of the microbial community in full-scale industrial park WWTPs and highlights the critical role of microorganisms in the treatment of industrial wastewater.

Identification and prediction model of placenta-brain axis genes associated with neurodevelopmental delay in moderate and late preterm children.

BACKGROUND: Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The "placenta-brain axis" (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children. METHODS: The authors performed multivariate logistic regression models between MLPT and children's neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma'anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models. RESULTS: The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children. CONCLUSIONS: These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.

Associating phthalate exposure during pregnancy with preschooler's FMI, ABSI and BRI trajectories via putative mechanism pathways.

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into "rapidly increasing FMI" (4.71%) and "stable FMI" (95.29%) groups; ABSI trajectories were categorized as "decreasing ABSI" (32.74%), "stable ABSI" (46.55%), "slowly increasing ABSI" (13.26%), "moderately increasing ABSI" (5.27%) and "rapidly increasing ABSI" (2.18%) groups; BRI trajectories were categorized as "increasing BRI" (2.82%), "stable BRI" (19.85%), and "decreasing BRI" (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (ß = 0.111, 95% CI = 0.002-0.221), ABSI (ß = 0.145, 95% CI = 0.023-0.268) and BRI (ß = 0.046, 95% CI = -0.005-0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502-0.844) and MBP (OR = 0.717, 95% CI = 0.984-1.015) were linked to a decreased risk of "decreasing BRI" in children; there was a negative relationship between MBP and the "decreasing ABSI" group (OR = 0.667, 95% CI = 0.487-0.914), and MEP increased the risks of "slowly increasing ABSI" (OR = 1.668, 95% CI = 1.210-2.299) and "rapidly increasing ABSI" (OR = 2.522, 95% CI = 1.266-5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights.

Trimester-specific effects of maternal exposure to single and mixed metals on cord serum inflammatory cytokines levels: A prospective birth cohort study.

BACKGROUND: Cord blood inflammatory cytokines are vital in early-life programming. An increasing number of studies concern the effect of maternal exposure to different metal elements during pregnancy on inflammatory cytokines, but limited studies have explored the association between maternal exposure to mixed metals and cord blood inflammatory cytokine levels. METHODS: We measured serum concentrations of vanadium (V), copper (Cu), arsenic (As), cadmium (Cd), and barium (Ba) in the first, second, and third trimesters and eight cord serum inflammatory cytokines (IFN-γ, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and TNF-α) in 1436 mother-child dyads from the Ma'anshan Birth Cohort. Generalized linear models and Bayesian kernel machine regression (BKMR) were performed to assess the association of single and mixed metal exposure during each trimester with cord serum inflammatory cytokine levels, respectively. RESULTS: Regarding metal exposure in the first trimester, V was positively associated with TNF-α (ß = 0.33, 95 % CI: 0.13, 0.53); Cu was positively associated with IL-8 (ß = 0.23, 95 % CI: 0.07, 0.39); Ba was positively associated with IFN-γ and IL-6; As was negatively associated with IFN-γ and IL-17A; and Cd was negatively associated with IFN-γ, IL-1ß, IL-12p70, IL-17A, and TNF-α. BKMR revealed that exposure to metal mixtures in the first trimester was positively associated with IL-8 and TNF-α but negatively associated with IL-17A. Moreover, V contributed the most to these associations. Interaction effects were observed between Cd and As and between Cd and Cu with IL-8, and between Cd and V with IL-17A. Among males, As decreased inflammatory cytokines; among females, Cu increased inflammatory cytokine levels, whereas Cd decreased inflammatory cytokine concentrations. CONCLUSIONS: Maternal exposure to metal mixtures in the first trimester interfered with cord serum inflammatory cytokine levels. The associations of maternal exposure to As, Cu and Cd with inflammatory cytokines showed sex differences. Further studies are warranted to support the findings and explore the mechanism of the susceptibility window and sex-specific disparity.

The Addition of Hypomethylating Agents to Low-Intensity Induction Chemotherapy Does Not Improve Outcomes in Elderly Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study.

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5-22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0-17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8-41.9%) and 33.3% (95% Cl: 20.3-51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1-51.5%) and 55.4% (95% Cl: 40.5-67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2-20.6%) and 20.6% (95% Cl: 9.1-35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.

Combined effects of prenatal phthalate exposure on cardiometabolic risk score among 4- to 7-year-old children: MABC study.

There is currently no consensus about the impact of prenatal phthalate exposure on blood pressure and glycolipids in children. Few studies consider the health effects as an integrated indicator. The combined effect of multiple phthalate exposures is often ignored. Based on the Ma'anshan Birth Cohort, 2298 woman-child pairs were included in this study. Maternal urine was collected in each trimester to analyze 6 phthalate metabolites. The overall cardiometabolic risk (CMR) score was calculated based on serum glycolipids and blood pressure for children aged 4-7 years. A higher score represents a less favorable CMR profile. The restricted cubic spline model was used to explore the relationship between prenatal phthalate exposure and childhood CMR score. In addition, the quantile g-computation and the Bayesian kernel machine regression were used to evaluate the combined effect. The MBP exposure in the 1st trimester (MBP-1st) and the MEP-2nd were non-linearly associated with the CMR score (Fnonlinear = 3.28 and 5.60, Pnonlinear = 0.0378 and 0.0038, respectively). The MBP-3rd (Flinear = 5.31, Plinear = 0.0012) and the ∑LMWP-3rd (Flinear = 4.37, Plinear = 0.0045) were negatively associated with the score in a linear manner. The phthalate mixture in the 2nd trimester increased the score (psil = 0.1747, 95% CI = 0.0077-0.3416), with the MEP being the most common [weights = 0.5290; posterior inclusion probability (PIP) = 0.40]. The phthalate mixture in the 3rd trimester decreased the score (psil = -0.2024, 95% CI = -0.4097－0.0048), with the MEHP (weights = -0.5101; PIP = 0.14) and the MBP (weights = -0.3993, PIP = 1.00) being the greatest contributors. In conclusion, the MBP-1st and the MEP-2nd are non-linearly associated with the cardiometabolic risk in children. The MBP-3rd and the ∑LMWP-3rd decrease the childhood risk. The combined exposure to phthalate mixture in the second and third trimester elevates and decreases the risk of childhood cardiometabolism, respectively.

Association of maternal and cord blood barium exposure with preschoolers' intellectual function: Evidence from the Ma'anshan Birth Cohort (MABC) study.

OBJECTIVES: Barium is widely involved in drilling fluids, plastics, and personal care products. Although the neurodevelopmental toxicity of barium has been reported in animals, human data are scarce. This study aimed to investigate the effect of prenatal barium concentrations on preschoolers' intellectual function based on a birth cohort study. METHODS: A total of 2164 mother-child pairs from Ma'anshan city, China were included in this study. We measured serum barium concentrations in the first, second, and third trimesters and in cord blood. Intellectual function in children aged 3.0-6.0 years old was assessed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). Linear regression models were used to analyze the association between averaged barium exposure during pregnancy and intellectual function. Multiple informant models were performed to jointly test for differences in associations between four repeated barium exposure and intellectual function. All models were further stratified by child sex. RESULTS: Collectively, we observed significant inverse associations of average maternal barium exposure levels with verbal comprehension index (VCI), visual spatial index (VSI), processing speed index (PSI), and full-scale intelligence quotient (FSIQ) scores. Maternal serum log10-transformed barium levels in the second trimester were inversely associated with VCI [-2.33 (95%CI: -4.02, -0.64)], VSI [-2.30 (95%CI: -4.08, -0.52)], working memory index (WMI) [-2.09 (95%CI: -3.71, -0.46)], PSI [-2.23 (95%CI: -3.82, -0.65)], and FSIQ scores [-2.73 (95%CI: -4.23, -1.22)]. Prenatal barium exposure was inversely associated with VCI, VSI, WMI, PSI, and FSIQ in girls, except for the fluid reasoning index (FRI). Additionally, inverse associations were found between prenatal barium exposure and VSI, PSI, and FSIQ in boys. CONCLUSIONS: Prenatal barium exposure had detrimental effects on intellectual function in preschoolers and girls drove these inverse associations more than boys. The second trimester may be the critical window of neurotoxicity to barium exposure.

Association between prenatal metals exposure and blood pressure in 5-6 years children: A birth cohort study.

BACKGROUND: The trajectory of blood pressure (BP) from childhood to early middle age suggested that individuals with elevated BP in early childhood were more likely to be affected by cardiovascular disease in adulthood. Exposure to metals may affect BP in children, and pregnancy is a sensitive time for metal exposure. This study assessed the relationship between different stages of prenatal exposure to metals or metal mixtures and BP in children aged 5-6 years. METHODS: The study included 2535, 2680, 2534 mother-child pairs in three trimesters, from the Ma'anshan birth cohort study (MABC). We collected maternal blood samples during pregnancy and measured the serum levels of four metals (arsenic, selenium, cadmium, and mercury). BP was measured in children aged 5-6 years. A linear regression model and Bayesian kernel machine regression (BKMR) were used to explore associations between prenatal exposure to metals at different stages and multiple metal exposure with BP in children aged 5-6 years. RESULTS: Associations were observed between the arsenic in the third trimester and children's diastolic blood pressure (DBP) (ß = 0.88, 95% CI: 0.44, 1.33), systolic blood pressure (SBP) (ß = 0.72, 95% CI: 0.19, 1.24) and mean arterial pressure (MAP) (ß = 0.83, 95% CI: 0.42, 1.23), as well as between the mercury and children's DBP (ß = 0.65, 95% CI: 0.13, 1.16) and MAP (ß = 0.60, 95% CI: 0.14, 1.07). The BKMR analysis showed that multiple metals had a significant positive joint effect on children's DBP, SBP and MAP. A potential interaction between arsenic and mercury was observed (ß = -0.85, 95% CI: -1.62, -0.08). CONCLUSIONS: Exposure to arsenic and mercury during pregnancy was associated with altered BP in children. The third trimester may represent an important window of opportunity to reduce the effects of metal exposure on children's blood pressure and long-term health.