BACKGROUND This study evaluated the real-world diagnostic performance and limitations of noninvasive prenatal testing (NIPT) in detecting fetal copy number variations (CNVs) within a large multicenter cohort in Shaanxi Province. MATERIAL AND METHODS This retrospective observational study analyzed 18 525 cases of NIPT at the First Affiliated Hospital of Xi'an Jiaotong University, a referral center for NIPT, from June 2023 to November 2024. Karyotype analysis and CNV sequencing were conducted on the fetuses and/or parents, with follow-up on pregnancy outcomes. RESULTS Abnormal CNVs were detected in 218 cases (1.18%; 218/18525), of which 129 women (59.17%; 129/218) opted for invasive diagnostic confirmation from 38 hospitals in 7 prefectural-level cities. The positive predictive value (PPV) for aberrant CNVs following NIPT was only 48.06% (62/129; 95% CI, 39.4-56.7%), with 28.57% (18/62) possessing pathogenic CNVs. We noted that PPV estimates were based on self-selected confirmatory testing, which might inflate or deflate performance estimates. The detection efficiency varied significantly by chromosomal location; chromosome 18 showed the highest PPV at 83.33% (15/18; P<0.05), notably within the 18p11.23-p11.31 segment. Furthermore, smaller CNVs (<5 Mb) demonstrated a higher concordance rate (PPV 54.74%; 52/95) than larger fragments (>10 Mb). Regional analysis indicated Hanzhong and Xi'an demonstrated elevated PPVs, while Yulin showed the highest incidence of pathogenic CNVs. CONCLUSIONS NIPT demonstrates moderate performance for fetal CNV detection, with a PPV of approximately 48%. Its clinical utility is maximized when combined with ultrasound findings, which significantly increase the predictive value. The stakeholders should be aware of this limitation when interpreting results.

Background:The outlook for individuals dealing with metastatic or recurrent cervical cancer is still unfavorable, and existing biomarkers that assess the effectiveness of immune checkpoint inhibitors (ICIs) have certain drawbacks. Our objective was to assess the predictive importance of the combined neutrophil-to-lymphocyte ratio (Combined.NLR), incorporating both pre-treatment and post-treatment measurements in this patient population. Methods:This retrospective cohort analysis, performed at one center, encompassed 148 individuals diagnosed with metastatic or recurrent cervical cancer who underwent treatment with ICIs. Patients were categorized into the Combined.NLR groups according to the median neutrophil-to-lymphocyte ratio (NLR) values obtained before and after treatment. The relationship between the Combined.NLR and progression-free survival (PFS) was examined through Cox regression analysis. A prognostic nomogram that includes various factors was created. Results:The Combined.NLR was identified as an independent prognostic factor for PFS. Individuals classified in the poor group exhibited a notably increased risk of disease progression in comparison to those in the good group [hazard ratio (HR) = 1.355, 95% confidence interval (CI): 1.006-1.824, p = 0.046]. The nomogram, which integrated the Combined.NLR, histological type, PD-L1 expression, the count of previous treatment lines, and the presence of multi-organ metastasis demonstrated a concordance index of 0.70. Calibration curves showed a strong correlation between the predicted results and the actual outcomes. Conclusion:The Combined.NLR is a dynamic and readily accessible prognostic marker. The developed nomogram provides individualized risk prediction for individuals with metastatic or recurrent cervical cancer, potentially aiding clinical decision-making.

Investigating the association between maternal age, anti-Müllerian hormone (AMH) levels, and chromosomal abnormalities in early missed abortion (EMA) embryos, providing evidence for clinical risk stratification and intervention strategies. A retrospective cohort study was conducted, including 990 EMA diagnosed patients between June 2020 and December 2024. All patients underwent chorionic villus copy number variant sequencing (CNV-seq) after curettage. The study groups were defined as follows based on two criteria: (1) maternal age at miscarriage: <35, 35–39, and ≥ 40 years; and (2) serum AMH level within one year of enrollment: <1.1, 1.1–4.5, and ≥ 4.5ng/mL. Chromosomal abnormality detection rates and types were compared across groups. Overall, chromosomal abnormalities were detected in 58.59

Introduction: This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. Methods: HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. Results: The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (β = −0.43, 95% confidence interval [CI]: −0.76 to −0.12, p = 0.009), HBeAg (β = −195.15, 95% CI: −366.35 to −23.96, p = 0.027), and hemoglobin changes (β = −8.09, 95% CI: −15.54 to −0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (β = 73.9, 95% CI: 38.92–108.95, p < 0.001) and albumin (β = 2.73, 95% CI: 0.23–5.23, p = 0.033). Conclusion: The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.

Objective: This study was developed as a retrospective analysis of the rates of embryonic chromosomal abnormalities in cases of missed miscarriages during early pregnancy, with a focus on identifying associated factors as a means of clarifying the genetic basis for missed miscarriages and how this pregnancy outcome relates to a variety of clinical and demographic characteristics. Methods: The present study enrolled 1490 patients who had been diagnosed with missed miscarriage and underwent CNV-seq testing at the Jiangxi Maternal and Child Health Hospital from January 2020 through December 2022. Medical records were accessed to obtain clinical data pertaining to these miscarriage cases, and the results of chromosomal abnormality testing were analyzed. Results: Chromosomal abnormalities were detected in 63.76% of all missed miscarriages, and included instances of autosomal trisomy (68.38%), triploidy/polyploidy (11.68%), 45XO (10.84%), CNVs (8.84%), double/multiple trisomy (4.32%), sex chromosome trisomy/polyploidy (0.32%), and complex abnormalities (2.95%). An examination of the relationship between these chromosomal abnormalities and clinical characteristics revealed that chromosomal abnormality incidence rates were significantly related to maternal age, mode of conception, AMH levels, and the presence or absence of an embryonic/fetal heartbeat. Advanced maternal age, mode of conception, and lower AMH levels were associated with a greater risk of embryonic chromosomal abnormalities. Specifically, the rates of autosomal trisomy gradually rose with maternal age (P<0.05), whereas 45XO, CNVs, and triploidy/polyploidy detection rates declined with age (P<0.05). Declining ovarian reserve function was associated with higher rates of karyotypic abnormalities (P<0.05). Higher rates of karyotypic abnormalities were also evident in the natural conception (NC) group, as were rates of CNVs and trisomy/polyploidy (P < 0.01), whereas higher rates of autosomal trisomy were detected in the assisted reproductive technology (ART) group. No relationship between a history of spontaneous miscarriages and the incidence of embryonic chromosomal abnormalities was detected. Conclusion: Embryonic chromosomal abnormalities are the leading cause of early missed miscarriages. The present results indicate that advanced maternal age, declining ovarian reserve function, and mode of conception can all increase the risk of these chromosomal abnormalities. Age and the presence of a fetal/embryonic heartbeat may be related to the incidence of different types of chromosomal abnormalities, while a history of prior missed miscarriages is not related to the odds of embryonic chromosomal abnormalities.

We aimed to determine the peripheral blood mononuclear cell (PBMC) immune profiles of mid- and late-stage pregnant women to establish a foundation for studying pregnancy-related diseases. Peripheral blood samples were collected from three women each during mid- and late-stage pregnancy, and PBMCs were extracted for single-cell RNA sequencing (scRNA-seq). Peripheral blood samples were also collected for flow cytometry analysis to validate the analytical results. HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells significantly differed in quantitative ratio and gene transcript level between women at mid- and late-stage pregnancy. In late pregnancy, cell-to-cell communication was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," exhibited high XIST expression, a gene that may be involved in the regulation of immune-related gene transcription and translation, and insulin signaling pathway, during pregnancy. Monocytes exhibited significant proinflammatory and metabolic properties in mid- and late-stage pregnancy, respectively. Natural killer (NK) cells were mainly involved in T- and B-cell-mediated signaling pathways, and in T cell differentiation, in mid-pregnancy. Enhanced innate immunity of NK cells was observed. Moreover, NK cells expressed genes associated with diabetes-related pathways in late-stage pregnancy. To conclude, we present detailed changes in the immune response occurring in pregnant women from mid- to late-stage gestation, revealing significant differences in PBMC subtypes and molecular properties. These findings provide insights into the physiopathological mechanisms of chronic hepatitis B infection, systemic lupus erythematosus, and gestational diabetes mellitus underlying systemic immune responses during mid- and late-stage pregnancy. NEW & NOTEWORTHY There are significant differences in three subtypes of memory/effector T cells (HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells) between mid- and late pregnancy. In late pregnancy, intercellular interaction was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," may be involved in the regulation of immune-related gene transcription and translation with a strong female bias.

BACKGROUND:Mother-to-child is the main route of the transmission of hepatitis B virus (HBV) infection. Tenofovir fumarate (TDF) antiviral treatment has become the most extensive choice worldwide. However, the effects of TDF treatment on the immune function of pregnant women remains unclear. Here we investigate the effect of TDF treatment on the immune microenvironment of pregnant women with HBV infection using single-cell RNA sequencing (scRNA-seq). METHODS:Three HBV-infected pregnant women were treated with TDF and six samples were collected before and after the treatment. In total, 68,200 peripheral blood mononuclear cells (PBMCs) were extracted for 10 × scRNA-seq. The cells were clustered using t-distributed stochastic neighbor embedding (t-SNE) and unbiased computational informatics analysis. RESULTS:The analysis identified four-cell subtypes, including T cells, monocytes, natural killer (NK) cells, and B cells, and unraveled the developmental trajectory and maturation of CD4+ T and CD8+ T cell subtypes. The cellular state and molecular features of the effector/memory T cells revealed a significant increase in the inflammatory state of CD4+ T cells and the cytotoxic characteristics of CD8+ T cells. Additionally, after TDF treatment, the monocytes showed a tendency for M1 polarization, and the cytotoxicity of NK cells was enhanced. Furthermore, the analysis of intercellular communication revealed the interaction of various subtypes of cells and the heterogeneous expression of key signal pathways. CONCLUSIONS:The findings of this study reveal significant differences in cellular subtypes and molecular characteristics of PBMCs of pregnant women with HBV infection before and after TDF treatment and demonstrate the recovery of immune response after treatment. These findings could help develop immune intervention measures to control HBV during pregnancy and the puerperium period.

There is a growing body of evidence that innate immunity also plays an important role in the progression of hepatitis B virus (HBV) infection. However, there is less study on systematically elucidating the characteristics of innate immunity in HBV-infected pregnant women. We compared the features of peripheral blood mononuclear cells in three healthy pregnant women and three HBV-infected pregnant women by single-cell RNA sequencing. 10 DEGs were detected between groups and monocytes were the main expression source of most of the DEGs, which involved in the inflammatory response, apoptosis and immune regulation. Meanwhile, qPCR and ELISA were performed to verify above genes. Monocytes displayed immune response defect, reflecting poor ability of response to IFN. In addition, eight clusters were identified in monocytes. We identified molecular drivers in monocytes subpopulations.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes were featured with different gene expression pattern and biological function.TNFSF10+ monocytes and MT1G+ monocytes were characterized by high levels of inflammation response.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes showed decreased response to IFN. Our results dissects alterations in monocytes related to the immune response of HBV-infected pregnant women and provides a rich resource for fully understanding immunopathogenesis and developing effective preventing HBV intrauterine infection strategies.

Objective: To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa. Methods: A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared. Results: (1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95%CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 (P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 (P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion (P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions: In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

Background Liver metastasis (LM) is an independent risk factor that affects the prognosis of patients with ovarian cancer; however, there is still a lack of prediction. This study developed a limit gradient enhancement (XGBoost) to predict the risk of lung metastasis in newly diagnosed patients with ovarian cancer, thereby improving prediction efficiency. Patients and Methods. Data of patients diagnosed with ovarian cancer in the Surveillance, Epidemiology, and Final Results (SEER) database from 2010 to 2015 were retrospectively collected. The XGBoost algorithm was used to establish a lung metastasis model for patients with ovarian cancer. The performance of the predictive model was tested by the area under the curve (AUC) of the receiver operating characteristic curve (ROC). Results The results of the XGBoost algorithm showed that the top five important factors were age, laterality, histological type, grade, and marital status. XGBoost showed good discriminative ability, with an AUC of 0.843. Accuracy, sensitivity, and specificity were 0.982, 1.000, and 0.686, respectively. Conclusion This study is the first to develop a machine-learning-based prediction model for lung metastasis in patients with ovarian cancer. The prediction model based on the XGBoost algorithm has a higher accuracy rate than traditional logistic regression and can be used to predict the risk of lung metastasis in newly diagnosed patients with ovarian cancer.

目的 分析胎儿窘迫孕妇不同分娩方式的围生期相关影响因素,明确中转剖宫产、直接剖宫产和经阴道分娩的影响因素和结局.方法 选取2013年1月1日至2018年5月30日在西安交通大学第一附属医院产科以"胎儿窘迫"为诊断收住入院并分娩的孕妇948例作为研究对象,根据分娩方式的不同将孕妇分为引产中转剖宫产组(332例)、引产后经阴道分娩组(283例)和直接剖宫产组(333例)3组.收集与分娩方式选择相关影响因素的数据和资料,采用软件Epidata3.1进行数据录入,利用SPSS 24.0进行数据分析.结果 中转剖宫产组、经阴道分娩组及直接剖宫产组3组研究对象的产前数据(孕周、产次、胎儿双顶径、股骨长、腹围、羊水指数、S/D比值)差异均有统计学意义(P<0.05).3组间的产时数据胎盘和羊水情况比较差异有统计学意义(P<0.05),脐带情况差异无统计学意义(P>0.05).3组间新生儿的1-5-10 min Apgar评分、新生儿体重、是否转科及出院时间差异均有统计学意义(P<0.05).结论 应重视胎儿窘迫的诊断和处理,尤其要重视产前胎儿情况和羊水量的充分评估,加强产程中的胎儿监护,选择更合理的分娩方式,在保证母儿安全的前提下降低剖宫产率.

Extracorporeal membrane oxygenation (ECMO) is more widely used in critically ill patients, which has gained time for the recovery of cardiopulmonary function. The ECMO technology has undergone dramatic changes. New small-diameter catheters have simplified vascular access, and the application of long-lasting anticoagulant coatings has improved the ECMO system′s histocompatibility, reduced blood damage, and reduced inflammation and thrombosis. ECMO has become simpler and safer. Because some serious pregnancy and delivery complications may lead to heart or lung failure, the use of ECMO during the perinatal period has also increased. In this paper, the indications, complications and matters needing attention of ECMO during perinatal severe illnesses were discussed.

BACKGROUND:Currently, tenofovir disoproxil fumarate (TDF) treatment in pregnant women with hepatitis B virus (HBV) infection in the second trimester of pregnancy to reduce the HBV DNA load and block the mother-to-child transmission of HBV has become a consensus. An increasing number of studies have shown that lncRNAs play an important role in immune regulation; however, there are only a few studies on how lncRNAs affect the immune function of TDF-treated pregnant women with HBV infection.METHODS:The peripheral blood of pregnant women with HBV infection was collected before and after TDF treatment for whole-transcriptome sequencing; the differential expression of lncRNA MALAT1 in PBMCs and natural killer (NK) cells was verified by qRT-PCR. ELISA and flow cytometry were used to detect the effect of MALAT1 on NK-92 cells on IFN-γ secretion. Dual-luciferase reporter, qRT-PCR, and western blot analyses were used to verify the relationship between the expression levels of MALAT1, has-miR-155-5p and HIF-1α.RESULTS:After TDF treatment, the MALAT1 expression in the PBMCs of pregnant women with HBV infection, especially in NK cells, was significantly reduced. MALAT1 overexpression decreased IFN-γ secretion in NK-92 cells, while IFN-γ secretion increased after MALAT1 knockdown. Mechanistically, we identified MALAT1 as a competitive endogenous RNA that regulates HIF-1α expression by sponging has-miR-155-5p. Low HIF-1α expression resulted in increased IFNG expression in, and IFN-γ secretion by, NK cells.CONCLUSIONS:Thus, MALAT1 may play an important role in NK cell-mediated immunity in TDF-treated pregnant women with HBV infection by regulating the has-miR-155-5p/HIF-1α axis.

Introduction: Preeclampsia (PE) is a pregnancy-specific multisystemic syndrome. This study aimed to investigate the associations between angiotensinogen (AGT), methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF) polymorphisms, and PE in the Han Chinese population. Methods: We genotyped 26 single-nucleotide polymorphisms (SNP) in three genes by using QuantStudioTM 12 K Flex Real-Time PCR technology in 168 patients with PE and 204 healthy pregnant control subjects. The associations of tested polymorphisms with PE were analyzed at allele, genotype, and haplotype levels. Results: A common coding variant in MTHFR, rs2274976, was significantly associated with increased risk of PE in both allelic and genotype models (P < 0.05). The heterozygous genotypes of rs699 (G/A vs G/G) in AGT gene and rs3025035 (C/T vs C/C) in VEGF gene showed weak associations with increased PE risk, whereas the mutant homozygous genotype of rs3024987 (TT vs C/C) and the heterozygous genotype of rs3025039 (C/T vs C/C) in VEGF gene displayed weak associations with decreased PE risk (P < 0.05). Discussion: However, these weak associations lost significance after multiple testing correction. The results indicated that rs2274976 in MTHFR gene may contribute to the increased risk of PE in pregnant women. AGT and VEGF gene polymorphisms may not play a significant role in PE development.

Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

Background: Pregnancy-specific vitamin reference ranges are currently not available for maternal vitamin management during pregnancy. This study aimed to propose pregnancy-specific vitamin reference ranges and to investigate the factors influencing vitamin levels during pregnancy. Methods: A cross-sectional study that included pregnant women from 17 cities in 4 provinces in western China was conducted from 2017 to 2019. A total of 119,286 subjects were enrolled in the study. Serum vitamin A, vitamin D, and vitamin E levels were measured. A multivariable linear regression model and restricted cubic spline function were used to analyze the factors related to vitamin levels. Results: The reference ranges for vitamin A, D, and E levels were 0.22–0.62 mg/L, 5–43 ng/mL, and 7.4–23.5 mg/L, respectively. A linear relationship was found between vitamin E level and age (β = 0.004; 95% confidence interval [CI], 0.0037–0.0042; p < 0.001), and a nonlinear relationship was found between vitamin D ( p nonlinear = 0.033) and vitamin A levels and age ( p nonlinear < 0.001). Season, gestational trimester, and regions were related to the levels of the three vitamins in the multivariable models ( p < 0.05). Conclusions: The lower limit of vitamin A during pregnancy was the same as the reference value currently used for the general population. The reference ranges of vitamins D and E during pregnancy were lower and higher, respectively, than the currently used criteria for the general population. Vitamin A, D, and E levels differed according to age, season, gestational trimester, and region.

目的 研究乙型肝炎病毒X(HBx)蛋白与内皮生长因子受体(EGFR)启动子的关系,明确HBx蛋白激活EGFR/PI3K/p-Akt信号通路抑制滋养细胞凋亡及相关机制.方法 构建EGFR启动子质粒,通过荧光素酶活性检测HBx蛋白对EGFR启动子的调控作用;通过感染慢病毒颗粒构建EGFR过表达滋养细胞,使用shRNA转染EGFR过表达滋养细胞构建EGFR敲低滋养细胞,Western blotting及激光共聚焦成像分析EGFR/PI3K/p-Akt蛋白表达及定位,并通过流式细胞术分析滋养细胞凋亡情况.将HBV野生型质粒、HBx缺失突变型HBV质粒及HBx质粒瞬时转染至胎盘滋养细胞内,Western blotting检测细胞内HBx、PI3K/p-Akt蛋白表达,并通过流式细胞术分析滋养细胞凋亡情况.结果 在JEG-3细胞及HTR-8细胞中共转染HBx质粒与EGFR启动子质粒时,EGFR启动子荧光素酶表达较对照组显著增高(P<0.01);EGFR过表达组JEG-3细胞及HTR-8细胞的PI3K/p-Akt蛋白表达显著升高(P<0.01),细胞凋亡比例显著降低(均为P<0.05);敲低EGFR组的结果相反.HBx蛋白表达组JEG-3细胞及HTR-8细胞PI3K及p-Akt蛋白表达显著升高(均为P<0.05),细胞凋亡比例显著下降(均为P<0.05).结论 在胎盘滋养细胞内,HBx蛋白作用于EGFR启动子,从而激活EGFR/PI3K/p-Akt信号通路,抑制细胞凋亡.

The classification of preeclampsia has not been unified in the world, and different subtypes of preeclampsia have different pathogenesis, prognosis and treatment. Clarifying the classification of preeclampsia is helpful to study the pathophysiological mechanism of different subtypes of preeclampsia and reduces the occurrence of adverse outcomes for mothers and infants.

Hepatitis B virus (HBV) infection is a global epidemic. The main transmission route of chronic HBV infection is from mother to child, yet the mechanisms underlying HBV intrauterine infection remain unclear. In the present study, the effect and the mechanism underlying hepatitis B virus X antigen (HBxAg) on HBV replication and EGFR activation in trophoblasts was investigated. Serum samples from pregnant women with HBV infection were used to infect trophoblasts and HBxAg expression was detected using ELISA. HBV plasmids carrying either full length hepatitis B virus X (HBx) or HBx with a deletion mutation (ΔHBx) were transfected into trophoblasts and expression levels of HBV DNA, hepatitis B e-antigen and pregenomic (pg)RNA, and structural maintenance of chromosomes (Smc) 5/6 were assessed. The association between HBx and EGFR promoters was characterized using a luciferase reporter assay and EGFR/PI3K/phosphorylated (p)-AKT expression and apoptosis rate were also monitored. The results of the present study indicated that HBxAg expression increased with the increasing titre of HBV DNA (P<0.05). Compared with the wild-type group, the amount of HBV DNA in the supernatant and cells was significantly reduced (P<0.05) in the ΔHBx group and the intracellular HBeAg and pgRNA levels were also significantly decreased (P<0.05). In addition, Smc5/6 expression was also significantly decreased (P<0.05) when the intracellular HBx protein was expressed compared with mock-transfected cells. Co-transfection of HBx and EGFR promoter plasmids in JEG-3 and HTR-8 cells significantly elevated EGFR promoter driven luciferase expression relative to the control group (P<0.01). In EGFR overexpressing cells, the expression of PI3K/p-AKT was significantly increased, whereas the apoptosis rate was significantly decreased (P<0.05). These results were reversed in the EGFR-knockdown group. In conclusion, the present study demonstrated that HBx promotes HBV replication in trophoblasts via downregulation of Smc5/6, activates the EGFR promoter and inhibits trophoblast apoptosis via the PI3K/p-AKT downstream signalling pathway, thereby increasing the risk of HBV intrauterine infection.

PURPOSE:The aim of this study was to compare the differences in the immune microenvironment between HBV-infected pregnant women with a high HBV viral load and healthy pregnant women, with an emphasis on T cell subset alteration.PATIENTS AND METHODS:We compared the differences of cellular and molecular signatures between HBV-infected and healthy pregnant women by performing single-cell RNA and T cell receptor sequencing of peripheral blood mononuclear cells from 51,836 women in the mid-trimester pregnancy stage. Specific trajectories of the different T clusters throughout the course of T cell differentiation were investigated. Flow cytometry was used to validate the proportion of different T cell subtypes.RESULTS:We identified nine cellular subtypes and found an increased proportion of effector/memory CD8+ T cells in HBV-infected pregnant women. Both CD4+ and CD8+ effector/memory T cells in HBV-related samples expressed higher levels of metallothionein (MT)-related genes (MT2A, MTIE, MTIF, MTIX), metal ion pathways, and multiple inflammatory responses. Among CD8+ T cell clusters, we identified a particular subset of effector/memory CD8+ T cells (CD8-cluster 2) with MTs as the top-ranking genes, which may be enriched in HBV-related samples. These cells showed an increased clonal expansion in HBV infection. Moreover, we found more active immune responses, according to cellular interaction patterns, between immune cell subsets in HBV-infected samples.CONCLUSION:This study shows significant differences between HBV-infected and healthy samples, including cell clusters, dominant gene sets, T cell function, clonal expansion, and V/J gene usage of T cell clonotypes, and identifies a distinct CD8+ T cell cluster with immune-active and antiviral properties. These findings pave the way for a deeper understanding of the impact of HBV infection on the immune microenvironment during pregnancy.