Background:Bisphenol A (BPA), a typical endocrine-disrupting chemical, is implicated in the pathogenesis of Polycystic Ovary Syndrome (PCOS); however, the underlying molecular mechanisms and pathophysiological processes remain unclear. This study aims to decipher molecular interactions between BPA and PCOS-related genetic networks, and to determine the combinatorial impacts of environmental pollutants on PCOS progression. Methods:We first identified overlapping genes associated with bisphenol A (BPA) exposure and polycystic ovary syndrome (PCOS) using the Comparative Toxicogenomics Database (CTD). Differentially expressed genes (DEGs) were extracted from three Gene Expression Omnibus (GEO) datasets, while oxidative stress- and apoptosis-related genes were retrieved from the GeneCards database. Subsequently, a series of in silico analyses were performed, including protein-protein interaction (PPI) network construction, functional enrichment profiling, Gene Set Enrichment Analysis (GSEA), immune infiltration evaluation, nomogram development, CB-DOCK molecular docking, and single-cell RNA-seq analysis of the mouse ovarian dataset GSE268919 (DHEA-induced PCOS-like model) to provide cell-type-resolved evidence. Finally, in vitro validation was conducted using primary granulosa cells from PCOS patients and healthy controls, as well as KGN cells, to assess hub gene expression. Functional evaluations were carried out via CCK-8 assay, flow cytometry, quantitative polymerase chain reaction (qPCR), and Western blotting. Results:We identified 139 hub genes between BPA exposure and PCOS, with enrichment in hormone metabolism, ovarian steroidogenesis, and reproductive signaling pathways-among which the apoptotic pathway was prominently associated with these hub genes, indicating BPA exerts a profound impact on cell survival in PCOS. Five hub genes (PTAFR, RACGAP1, CYP19A1, FSHR, DMD) were pinpointed, and a nomogram integrating these genes showed robust PCOS predictive accuracy. Single-gene GSEA further linked the hub genes to immune modulation, inflammation, and cell apoptosis-validating their functional relevance to apoptotic processes in PCOS. Immune cell infiltration analysis revealed discrepancies between PCOS and control groups, with hub genes correlating with specific immune subsets (e.g., pro-inflammatory cells) that may exacerbate apoptotic signaling in ovarian tissues. Molecular docking demonstrated strong binding affinity between BPA and the protein products of hub genes, suggesting direct BPA-mediated interference with their roles in regulating cell apoptosis. In the mouse ovarian scRNA-seq dataset (GSE268919), we observed cell-type-specific dysregulation of Cyp19a1 and Dmd (mouse gene symbols), with stress/apoptosis signatures enriched in specific ovarian cell populations, thereby providing supportive cell-type localization for the hub-gene-associated phenotypes. In vitro validation confirmed dysregulated expression of hub genes in PCOS primary granulosa cells; BPA treatment dose-dependently regulated hub gene expression, inhibited KGN cell proliferation, and significantly induced granulosa cell apoptosis. Conclusion:BPA exposure disrupts granulosa cell survival in PCOS by driving apoptosis-related molecular reprogramming through key gene regulation, thereby elucidating mechanistic links between environmental pollutants and PCOS progression and highlighting potential molecular targets for intervention.

Paromomycin, a broad-spectrum aminoglycoside antibiotic, is widely used in both clinical and agricultural fields. However, its environmental impact and potential developmental toxicity have raised growing concerns. This study systematically evaluates the adverse effects of paromomycin on early cardiovascular development in zebrafish embryos from multiple biological perspectives. Zebrafish embryos were exposed to environmental concentrations of paromomycin (0, 0.3, 3, 30, and 300 μg/mL) for 5 days. Comprehensive assessments were then performed through morphological observations, cardiovascular phenotype analysis, behavioral evaluations, and integrated analysis. The results revealed that exposure to paromomycin induced dose dependent developmental damage, including decreased survival rates, delayed hatching, and increased malformation rates. Detailed cardiovascular assessments confirmed significant abnormalities in both cardiac function and vascular development. Molecular level investigations further elucidated the underlying mechanisms, showing that paromomycin exposure elevated reactive oxygen species levels, triggering oxidative stress, inducing apoptosis in the pericardial region, and disrupting the expression of key cardiovascular developmental genes. Integrating network toxicology, molecular docking, and transcriptomic analyses, this study identified six key signaling pathways involved in paromomycin induced cardiovascular toxicity. These findings provide a comprehensive mechanistic framework for understanding the developmental cardiovascular toxicity of paromomycin at environmentally relevant concentrations and offer valuable insights for the safe application and risk management of this widely used antibiotic.

Polycystic ovary syndrome (PCOS) is increasingly viewed as an environmentally influenced, epigenetically mediated reproductive–metabolic disorder. Bisphenol A (BPA) exposure is higher in women with PCOS and has been linked to hyperandrogenism, insulin resistance and ovarian dysfunction, while N6-methyladenosine (m6A) dysregulation contributes to granulosa cells (GCs) proliferation and apoptosis. However, the downstream gene networks that integrate BPA exposure, m6A imbalance and GCs apoptosis in PCOS remain unclear. BPA-related genes were retrieved from the Comparative Toxicogenomics Database and intersected with PCOS differentially expressed genes from four GEO GC datasets (GSE34526, GSE137684, GSE102293, GSE80432) and m6A/apoptosis-related genes from GeneCards. Protein–protein interaction, GO/KEGG enrichment, GSEA and immune-cell infiltration (ssGSEA) analyses were performed. A five-gene logistic model and nomogram were built and externally validated in GSE106724 and GSE98595. Single-cell RNA-seq data (GSE268919) were used to map hub-gene expression, m6A and apoptosis signatures across ovarian cell types. Molecular docking (AutoDock Vina) evaluated BPA–protein binding. Hub-gene expression and function were verified in primary human GCs and BPA-treated KGN cells by qPCR, Western blot, CCK-8 and flow cytometry. We identified 139 BPA–PCOS shared genes and five hub genes—LIFR, LMNA, BCL2, ADM, S100P—enriched in ovarian steroidogenesis, oxidative-stress and apoptotic pathways. These genes showed distinct expression patterns between PCOS and controls and were associated with altered immune-cell infiltration. A five-gene nomogram achieved an AUC of 0.846 in the training set and 0.791 in an external validation cohort, with good calibration and decision-curve benefit. Single-cell analysis revealed LIFR downregulation and LMNA upregulation in GCs clusters with high m6A and apoptosis scores. Docking predicted moderate-to-strong BPA binding to all five proteins. In vitro, BPA reduced GCs viability, increased apoptosis with BAX/Caspase-3 activation, and reproduced the hub-gene dysregulation observed in PCOS GCs. Our integrative data support a BPA–m6A–apoptosis axis in PCOS and identify a five-gene granulosa-cell signature with potential diagnostic utility, providing mechanistic insight and candidate targets for environmentally driven PCOS; however, its clinical utility requires validation in larger, independent and prospectively recruited cohorts. This work is an observational and experimental laboratory study and not a clinical trial.

OBJECTIVE:This study aims to analyze prenatal diagnostic indications, methods, and prognosis of fetuses with mosaicism, providing a reference for related prenatal diagnosis and genetic counseling. METHOD:Cases of fetuses prenatally diagnosed with mosaicism via amniocentesis at our center over a 3-year period were retrospectively reviewed. The review covered maternal age, prenatal ultrasound phenotypes, results of whole-genome non-invasive prenatal testing (wgNIPT), and outcomes of prenatal diagnosis, including karyotype analysis, chromosomal microarray (CMA), and fluorescence in situ hybridization (FISH). Pregnancy outcomes and postnatal phenotypes were also examined. RESULTS:Among the 37 cases reviewed, 43% (16/37) involved women of advanced maternal age (≥35 years), while 22% (8/37) exhibited ultrasound abnormalities. Of the subset of 31 cases that underwent wgNIPT prior to amniocentesis, 94% (29/31) had results concordant with prenatal diagnostic findings. A total of 35 cases were analyzed using multiple techniques, with 17 showing consistent findings, 10 discrepancies in mosaic or non-mosaic status, and 8 conflicting results across methods. Thirteen cases resulted in live births with no apparent abnormalities detected in follow-ups at ages 3-5. CONCLUSION:wgNIPT is a valuable tool for prenatal mosaicism screening, although its detection of complex cases remains limited. Prenatal diagnosis of mosaicism requires the mutual verification of multiple genetic techniques. Postnatally, mosaicism might lack apparent phenotypes; prolonged monitoring is needed to detect delayed effects.

The relationship between maternal cholesterol deficiency and the risk of congenital heart defects (CHDs) in offspring is not fully understood. In a birth cohort study of 5041 family trios, we found that low maternal cholesterol levels were significantly associated with an increased risk of CHD, with RRs of 1.52 in the second trimester and 1.73 in the third trimester. To further investigate this link, we treated pregnant mice with cholesterol-lowering agents, namely, ezetimibe or atorvastatin. Both treatments led to a significant increase in the incidence of CHD in offspring. To identify a pathogenic variant that could provide genetic evidence linking cholesterol synthesis to CHD occurrence and serve as a target for constructing a genetic mouse model, we performed whole-genome sequencing (WGS) on 103 CHD cases from the birth cohort. We identified a recurrent functional variant in the CYP51A1 gene (c.1147 A > G, p.Ile383Val). We then developed a Cyp51I383V knock-in mouse model. This variant disrupted cholesterol synthesis, resulting in CHD through impaired hedgehog (Hh) signaling. Most intriguingly, maternal dietary intervention to increase cholesterol intake effectively reduced the risk of CHD in Cyp51I383V mutant offspring. Our study suggests that low maternal cholesterol during pregnancy increases the risk of CHD in offspring by inhibiting Hh signaling and that maternal cholesterol supplementation during pregnancy may reduce the occurrence of CHD.

Neomycin, a widely used aminoglycoside antibiotic, poses potential risks to organism and the environment that remain incompletely evaluated. This study systematically evaluates its toxic effects on zebrafish embryos across physiological, cellular, molecular, and behavioral dimensions. At the physiological level, neomycin exposure induces severe developmental abnormalities, including yolk sac edema, reduced body length, and craniofacial malformations. Developmental disorders of the cardiovascular and hematopoietic systems are confirmed in exposed larvae. In addition, zebrafish larvae exposed to neomycin exhibit significant locomotor deficits, including reduced swimming speed, distance traveled, and impaired responsiveness to light-dark stimulation, indicating reduced activity. Mechanically, neomycin triggers oxidative stress through a dose-dependent elevation of reactive oxygen species (ROS) levels and induces cellular apoptosis through the PI3K/Akt signaling pathway. Collectively, our findings demonstrate that neomycin exerts toxic effects on zebrafish embryonic development, highlighting concerns regarding neomycin exposure risks during early pregnancy and providing critical insights into its potential environmental hazards.

The association between the composite dietary antioxidant index (CDAI) and hyperlipidemia remains unclear. Therefore, this study aimed to investigate the relationship between CDAI and hyperlipidemia. The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) dataset spanning from 2005 to 2020. Based on 24-h dietary recall interviews, the CDAI was calculated using the intake of six dietary antioxidants. Univariate and multivariate logistic regression models were employed to investigate the relationship between CDAI and the occurrence of hyperlipidemia. Additionally, restricted cubic spline (RCS) analysis was utilized to investigate potential non-linear relationships between the CDAI and risk of hyperlipidemia. The final analysis included 30,788 adults in the United States, among whom 25,525 (82.91%) were diagnosed with hyperlipidemia. A significant negative correlation was observed between the CDAI and hyperlipidemia in the unadjusted (Odds ratio [OR] 0.97 [95% CI 0.96, 0.98]) and multi-variable adjusted (OR 0.98 [95% CI 0.97, 0.99]) models. When the CDAI values were analyzed as a categorical variable, individuals in the highest quartile (OR 0.82 [95% CI 0.73, 0.92]) exhibited a nearly one fifth decreased risk of hyperlipidemia compared to those in the lowest quartile. Additionally, RCS analysis revealed a linear relationship between CDAI and hyperlipidemia (P for nonlinearity = 0.124). The results remained consistent across subgroups except for individuals under the age of 60 or those with diabetes mellitus. There was a significant negative correlation between the CDAI and risk of hyperlipidemia, indicating that maintaining an optimal CDAI level could effectively reduce the incidence of hyperlipidemia.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Fetal digestive system malformations (DSMs) are correlated with chromosomal anomalies. The prenatal diagnosis of DSMs allows for timely treatment and reduces perinatal morbidity and mortality. However, genetic screening for fetal DSMs is rarely reported. This study aimed to investigate genetic etiology and pregnancy outcomes in cases of fetal DSM by analyzing correlations between DSM types and chromosomal anomalies. This retrospective single-center study included 126 fetuses in whom DSMs were detected via prenatal ultrasonography. Genetic etiology was investigated using conventional karyotyping, chromosome microarray analysis (CMA), and whole-exome sequencing (WES). DSMs were categorized as simple DSM (Group A), DSM combined with abnormal ultrasound soft markers (Group B), and DSM combined with comorbidities of other systems (Group C). Abnormal karyotypes were detected in 11/126 (8.7 %) fetuses. Four more pathogenic copy number variants (CNVs) were detected using CMA, increasing the detection rate to 11.9 %. The detection rates significantly differed between the three DSM types (1.78 %, 8.11 %, and 33.33 % in Groups A, B, and C, respectively). The overall adverse pregnancy outcome rate was 33.9 %, and 11.5 %, 23.5 %, and 81.3 %, (P < 0.001), respectively, in Groups A, B, and C. Out of 83 live births, three neonates died, 26 underwent postnatal surgery with 24 favorable outcomes, and 54 did not undergo surgery and were basically normal. Two neonates who underwent WES were diagnosed with CHD7-associated Charge syndrome and JAG1-associated Alagille syndrome, respectively. Our findings demonstrate that fetal DSM is closely related to chromosome aneuploidies, CNVs, and point mutations. The prognoses of most fetuses with simple DSM and those with comorbid abnormal ultrasound soft markers were favorable in the absence of chromosomal anomalies and severe structural malformations, provided they underwent timely surgery as neonates. These findings provide guidance for the prenatal diagnosis and clinical management of fetal DSMs and the genetic counseling of parents.

Purpose: Hypoxia plays an essential role in the progression of hepatocellular carcinoma (HCC), whereas hypoxia inducible factor-1 (HIF-1) is the key transcription factor allowing HCC to survive hypoxia. The aim of this study was to define the essential mRNAs and miRNAs regulated by HIF1A and dissect their functions, interactions, and tumor-infiltrating immune cells in HCC. Methods: A human HCC cell line HepG2 was used as a cell model of HCC. The CRISPR/Cas9 system was used to knock out HIF1A in HepG2 cells, and RNA sequencing was utilized to characterize differentially expressed mRNAs and miRNAs in the HIF1A-knockout HepG2 cells; the identified candidates were then analyzed by GO annotation and KEGG pathway enrichment to study their function and establish a PPI network. Quantitative (q) PCR was used to verify if there were significant differences in the expression of mRNAs, and the association of the selected mRNAs expression with immune cell infiltration levels was further analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. Results: Using RNA-sequencing, we discovered that there were 1535 mRNAs differentially expressed (adjusted p < 0.05, |fold change|>1.5) in the HIF1A-knockout HepG2 cells, among which there were 644 mRNAs upregulated and 891 mRNAs downregulated. GO annotation and KEGG pathway enrichment showed that these mRNAs were involved in glycolysis/gluconeogenesis, PI3K-Akt signaling pathways, and HIF-1 signaling pathways. In addition, we found that there were 309 miRNAs differentially expressed (adjusted p < 0.05, |fold change|>1.5) in the HIF1A-knockout HepG2 cells, of which there were 213 miRNAs upregulated and 96 miRNAs downregulated. Our further analyses uncovered that these miRNA putative targets were involved in the hippo signaling pathway, axon guidance, and tight junction. Moreover, the construction and analysis of the PPI network showed that OASL, IL6, and TAF1 were recognized as hub genes with the highest connectivity degrees. Importantly, in the HIF1A-knockout HepG2 cells, our qRT-PCR data confirmed the selected mRNA changes revealed by RNA-sequencing, and with TCGA pan-cancer data, we revealed that the expressional levels of these three genes, LUM, SCOC, and CCL2, were associated with immune cell infiltration levels. Conclusion: The identified potential key network of mRNAs and miRNAs regulated by HIF1A in the HCC cells suggests a key role of HIF1A in the tumorigenesis of HCC.

Recently, chromosomal microarray analysis (CMA) has been implemented as a first-tier test in pregnancies with ultrasound anomalies. However, its application for pregnancies with abnormal maternal serum screening (AMSS) only is not widespread. This study evaluated the value of CMA compared to traditional karyotyping in pregnancies with increased risk following first- or second-trimester maternal serum screening. Data from 3973 pregnancies with referral for invasive prenatal testing following AMSS were obtained from April 2016 to May 2020. Routine karyotyping was performed and single nucleotide polymorphism array was recommended. The foetuses were categorized according to the indications as AMSS only (group A) and AMSS with ultrasound anomalies (group B). CMA was performed on 713 prenatal samples. The proportion of women opting for CMA testing in both groups increased over the years. The incremental yield of clinically significant findings for pregnancies with high risk of screening results was similar to that for the foetuses with ultrasound soft markers (P > 0.05), but significantly lower than that for the foetuses with structural anomalies (P < 0.05). The total frequencies of variants of unknown significance in groups A and B showed no significant difference (P > 0.05). CMA should be performed for pregnant women undergoing prenatal invasive testing due to AMSS, especially with high-risk results, regardless of ultrasound findings.

出生缺陷目前已成为影响人口素质和群体健康水平的公共卫生问题,是引起新生儿残疾、疾病甚至死亡的主要原因之一,严重影响了社会文明和人口素质的发展.开展围孕期保健可降低出生缺陷发生率.

目的:研究影响患病宫颈高级别鳞状上皮内病变(HSIL)风险的相关因素并构建患病风险预测模型,为临床实践提供参考.方法:选取2019年6月至2021年1月于福建省妇幼保健院诊治的慢性宫颈炎、低级别鳞状上皮内病变(LSIL)、HSIL及宫颈癌病例为研究对象,回顾性收集其阴道镜检查结果(醋酸白色上皮、镶嵌、点状血管等)、HPV检测结果(HPV16、31、33、58型是否阳性)及病理诊断结局等资料,分析罹患HSIL或宫颈癌的风险与阴道镜检查结果及HPV检测结果间的关联性,运用SAS9.4软件的logistic逐步回归分析方法筛选影响患病风险的相关因素并构建患病风险预测模型.结果:共纳入研究对象5147例,其中慢性宫颈炎占59.74％(3075/5147),LSIL占23.33％ (1201/5147),HSIL占15.00％ (772/5147),宫颈癌占1.92％ (99/5147).研究对象患HSIL或宫颈癌的风险与其临床症状,醋酸白色上皮、镶嵌或点状血管,HPV16、31、33或58型阳性情况等8个纳入因素在单因素分析时均存在显著关联(P均＜0.001).研究因素间,仅镶嵌与点状血管间的列联系数值相对较大(0.36).采用逐步回归法构建多变量logistic模型,则依次纳入点状血管、HPV16型阳性情况、醋酸白色上皮、HPV33型阳性情况、HPV58型阳性情况、镶嵌、HPV31型阳性情况,无剔除变量,该模型对训练样本预测的正确率为71.7％,模型的拟合优度良好.利用该模型可对不同HPV检测结果和(或)阴道镜检查结果患者的患病风险进行预测.结论:阴道镜检查结果及HPV检测结果均与患HSIL或宫颈癌风险存在关联性;综合阴道镜检查结果及HPV检测结果构建的患病风险预测模型可为临床实践提供参考;HPV16、31、33、58型的多重感染与宫颈病变严重程度间关系密切.

目的 探讨子宫肌壁间妊娠的临床表现、发病因素、诊断及治疗方案.方法 回顾性分析2002年1月至2020年1月福建省妇幼保健院收治的11例子宫肌壁间妊娠患者的病史及诊治经过,探讨子宫肌壁间妊娠的病因、诊断及治疗方案.结果 11例患者中9例被误诊为宫内妊娠、宫角妊娠、输卵管妊娠或妊娠滋养细胞疾病.3例接受药物保守治疗,其中1例中转手术;8例接受宫腹腔镜手术治疗.11例患者治疗后血人绒毛膜促性腺激素(β-hC G)均降至正常范围.结论 子宫肌壁间妊娠无特异的临床表现,对于有子宫手术史,而影像学检查提示子宫肌层占位的患者应高度警惕,宫腹腔镜探查可明确诊断同时清除病灶.

Background: Low HbA(2)level is an underlying of delta-thalassemia, alpha-thalassemia, and IDA. Interactions of these disorders can generate a wide spectrum of phenotype, which will pose diagnostic conundrum for clinical assessment, carrier screening, and genetic counseling. Methods: Subjects with HbA(2)levels below 2.0% with normal or reduced hematological parameters were recruited for further investigation. delta-globin gene mutations were identified by DNA sequencing of the HBD gene. Serum ferritin (SF) concentration was determined by the chemiluminescent microparticle immunoassay. The three common deletional alpha-thalassemia (--(SEA)/alpha alpha, -alpha(3.7)/alpha alpha, and -alpha(4.2)/alpha alpha) were detected using Gap-PCR, detection of the point mutations in the three nondeletional alpha-thalassemia (alpha(CS)alpha/alpha alpha,alpha(QS)alpha/alpha alpha,alpha(WS)alpha/alpha alpha), and the 17 common beta-thalassemia was performed using reverse dot blot hybridization (RDB). Results: We had characterized the delta-globin gene mutations in 20 cases, revealing a frequency of 0.4% in the women of reproductive age (20/4 792). Two previously known mutations:-77 T > Cand-30 T > Cand 3 novel delta-globin gene defects:-44G > A,CD87C > T,andCD134T > Awere found. In the selected cases, we also found 85 cases confirmed with (51.2%,85/166) IDA and 39 cases (23.5%,39/166) with common alpha-thalassemia. Subjects with delta-thalassemia had statistically higher levels of Hb, MCV, and MCH compared with other two groups, whereas statistically lower levels of RDW were seen in delta-thalassemia group. What's more, statistically higher levels of SF were seen in delta-thalassemia group, compared with IDA groups. Conclusion: We reported the spectrum of delta-thalassemia mutations for the first time with the frequency of 0.4% among women of reproductive age in Fujian area and found that-77T > Cmutation was the most common mutation, followed by-30T > Cmutation. What's more, 3 novel delta-globin gene defects:-44G > A,CD87C > TandCD134T > Awere found. A thorough analysis of the hematological, electrophoretic characterization, and the level of SF was needed to suspect and further investigate the existence of IDA, alpha-thalassemia, and delta-thalassemia.

Background The incidence of CHD is the highest among birth defects and is increasing year to year. CHD seriously harms the health of infants and young children and presents a large economic burden to families and society. The pathogenesis of CHD and preventive measures are the focus of current research. Our research aimed to explore the intervention effect of folic acid on heart abnormalities resulting from sodium arsenic (NaAsO2) exposure during the periconception period. Methods Sixty 35-day-old female SD rats were randomly divided into 5 groups with 12 rats in each group. Group A was the control group. The rats were given distilled water and ordinary chow. The rats in group B were given distilled water containing 75 mg/L NaAsO2 and ordinary chow. The rats in groups C, D, and E were given distilled water containing 75 mg/L NaAsO2 and chow containing 0.53 mg/kg, 5.3 mg/kg, and 10.6 mg/kg folic acid, respectively. The general condition of the embryos and the histopathology of the embryonic hearts were examined. The acetylation levels of histone H3K9 in heart tissues and the expression levels of Mef2C (which is related to heart development) were observed. Results The embryo weight and placental weight of groups B-E were significantly lower than those of group A (P < 0.05). The heart malformation rate of the fetal rats in groups B-E was significantly higher than that of the fetal rats in group A (P < 0.05). We found that the level of H3K9 acetylation in fetal rat cardiomyocytes in groups B-E was significantly higher than that in group A (P < 0.05) and that the level of H3K9 acetylation in groups C-E was lower than that in group B (P < 0.05). The mRNA level of Mef2C in fetal rat cardiomyocytes in group B-E was significantly higher than that in group A (P < 0.05), and the mRNA level of Mef2C in groups C-E was significantly lower than that in group B (P < 0.05). Conclusion Supplementation with folic acid during the periconception period can interfere with the toxic effects of arsenic on the heart. The mechanism may be that lowering the acetylation levels of histone H3K9 in heart tissues leads to decreased expression levels of Mef2C, which may play a protective role in heart development in fetal rats.

The q11.2 region on chromosome 22 contains numerous low-copy repeats that lead to deleted or duplicated regions in the chromosome, thereby resulting in different syndromes characterized by intellectual disabilities or congenital anomalies. The association between patient phenotypes and 22q11.2 copy number abnormalities has been previously described in postnatal cases; however, these features have not been systematically evaluated in prenatal cases because of limitations in phenotypic identification in prenatal testing. In this study, we investigated the detection rate of 22q11.2 copy number abnormalities in 2500 fetuses using single nucleotide polymorphism (SNP) array and determined the common abnormal ultrasound findings in fetuses carrying the 22q11.2 copy number abnormalities. The 22q11.2 copy number abnormalities were identified in 13 fetuses with cardiovascular malformations (6/13), kidney malformations (3/13), isolated ultrasound markers (3/13), or high-risk Down syndrome based on maternal serum screening (1/13). Approximately 0.5% (13/2500) of the fetuses harbored 22q11.2 copy number abnormalities. The most frequent ultrasound findings in fetuses with these abnormalities were cardiovascular malformations, followed by kidney malformations and isolated ultrasound markers. Prenatal diagnosis of these genetic abnormalities allows for the delineation of differential diagnoses, characterization of a wide spectrum of associated malformations, and determination of associations that exist between prenatal diagnosis and obstetrical outcomes.

Multiple molecular tests are currently needed for accurate carrier testing for thalassemia. Therefore, long-molecule sequencing (LMS) was evaluated as an alternate on the PacBio Sequel platform for genotyping carriers of α-thalassemia or β-thalassemia. Multiplex long PCR was used to generate representative amplicons for the α (HBA1/2) and β (HBB) gene loci. Following LMS, circular consensus sequencing reads were aligned to the hg19 reference genome and variants called using FreeBayes software version 1.2.0. In a blinded study of 64 known carrier samples, all HBA1/2 and HBB variants detected by LMS were concordant with those independently assigned by targeted PCR assays. For HBA1/2 carrier samples, LMS accurately detected the common South East Asian, -α3.7, and -α4.2 deletions and four different rare single-nucleotide variants (SNVs). For HBB carrier samples, LMS accurately detected the most common Chinese insertion and deletion variant c.126_129delCTTT and 14 different SNVs/insertions and deletions and could discriminate compound heterozygous SNVs (trans configuration) and identify variants linked to benign SNPs (cis configuration). Overall, LMS displayed the hallmarks of a scalable, accurate, and cost-effective genotyping method. With further test coverage to additionally include detection of other clinically significant HBA1/2 copy number variations, such as the Thai, Mediterranean, and Filipino deletions, LMS may eventually serve as a comprehensive method for large-scale thalassemia carrier screening.

BACKGROUND:Aortic arch abnormalities (AAA) are abnormal embryologic developments of the aorta and its branches. Their outcomes often depend on their association with other congenital diseases and genetic testing results.OBJECTIVE:This study aimed to evaluate the yield of chromosomal microarray analysis (CMA) in fetuses with different patterns of AAA and normal karyotype.METHODS:Data from 158 pregnancies referred for prenatal CMA testing due to fetal AAA were obtained between April 2016 and April 2019. Fetuses with isolated AAA, AAA accompanied by soft ultrasound markers, and AAA with other ultrasound malformations were classified into groups A, B, and C, respectively. Cases with detectable karyotype aberrations were excluded from the study.RESULTS:Twenty cases (12.7%) of submicroscopic anomalies were detected in 158 cases with normal karyotype, comprising 16 cases (10.1%) of clinically significant variants, two cases (1.3%) of variants of unknown significance, and two variants (1.3%) that were likely benign. Microdeletion of 22q11.2 accounted for 25% (4/16) of the clinically significant variants. The overall incremental yields by CMA in group A, group B, and group C were 1.8%, 2.3%, and 24.1%, respectively. Except for double aortic arch, the incremental yield of clinical significant findings for each type of AAA in group C was much higher than that in group A and group B. In group A, a clinically significant variant was only detected in one fetus with right aortic arch (RAA) (1.8%, 1/57).CONCLUSIONS:In addition to 22q11.2 microdeletion, many other clinically significant submicroscopic variants are present in fetuses with AAA, especially in fetuses with other ultrasound malformations. Although CMA is always recommended in the presence of any malformation in many countries, our results suggest insufficient evidence to recommend CMA in fetuses with isolated AAA, except for isolated RAA.

Early diagnosis of congenital heart disease (CHD) can improve the prognosis of neonates with CHD. We retrospectively evaluated the value of prenatal diagnosis of CHD by comparing the pregnancy outcomes. Prenatal diagnosis of CHD was established by echocardiographic evaluation of fetal heart. Amniotic fluid and/or cord blood genetic examination, pathological anatomy, casting specimen, and/or multidisciplinary-joint consultation (MDJC) were performed. A total of 1492 fetuses with CHD were diagnosed by prenatal echocardiography from 67834 pregnant women. There were 445, 236, 583, and 228 cases in groups A (simple CHD), B (simple CHD plus extra-cardiac abnormality), C (complex CHD), and D (complex CHD plus extra-cardiac abnormality), respectively. The pregnancy continuation rate in the four groups was 98.67%, 85.71%, 67.65%, and 36.84%, respectively ( P < 0.001). The pregnancy termination rate for fetal CHD with extra-cardiac abnormalities was significantly higher than that for fetuses with only CHD (81.24% vs . 53.6%, P < 0.05). Prenatal genetic test revealed chromosomal abnormalities in 20.43% of fetuses with CHD. MDJC significantly decreased the pregnancy termination rate. In 88 cases, the original decision to terminate the pregnancy was changed after consultation and the pregnancy was continued. Of these, 87 cases culminated in live births; 65 of these children had better prognosis. Nine-segment sequential segment analysis method for prenatal fetal echocardiography was compared with the results of pathological anatomy, cast specimen, postoperative diagnosis, and postnatal ultrasound. The accuracy of prenatal ultrasound for diagnosis of fetal complex CHD and fetal simple CHD was 90.5–91.66% and 98.6%, respectively. Prenatal ultrasound is still the most effective method for fetal CHD diagnosis.