Cervical insufficiency (CI) affects 0.1%-2% of pregnancies and represents a significant cause of second-trimester pregnancy loss and preterm birth; yet, its pathophysiology remains incompletely understood. This study investigated whether aquaporin-3 (AQP3) facilitates hydrogen peroxide (H₂O₂) transport into cervical macrophages, driving their polarization toward a pro-inflammatory phenotype and subsequent cervical matrix degradation. Cervical tissues from women with CI demonstrated 1.45-fold higher AQP3 expression compared to gestational age-matched controls, with increased colocalization with macrophages. Tissue H₂O₂ levels were elevated 2.43-fold in CI, accompanied by increased oxidative damage markers and reduced collagen content. In vitro studies using THP-1 macrophages revealed that AQP3 knockdown prevented intracellular H₂O₂ accumulation despite pro-inflammatory stimulation, blocking M1 polarization and NF-κB activation. Co-culture experiments demonstrated that AQP3-dependent M1 macrophages increased matrix metalloproteinase (MMP)-9 activity 3.8-fold and reduced fibroblast collagen content by 59%. Both H₂O₂ scavenging with PEG-catalase and NF-κB inhibition with Bay 11-7082 prevented macrophage-mediated matrix degradation. These findings suggest that AQP3 may serve as an important mediator linking oxidative stress to inflammatory cervical remodeling through facilitation of H₂O₂ influx, NF-κB activation, and M1 macrophage polarization. Targeting AQP3 or its downstream signaling may represent a potential therapeutic approach that requires preclinical validation to prevent CI-associated pregnancy complications.

INTRODUCTION:Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by excessive inflammation at the maternal-fetal interface. The α7 nicotinic acetylcholine receptor (α7nAChR), a key mediator of the cholinergic anti-inflammatory pathway, is downregulated in decidual macrophages of PE patients, but the downstream mechanisms linking α7nAChR deficiency to macrophage inflammatory activation remain unclear. This study investigated whether α7nAChR deficiency promotes decidual macrophage M1 polarization through TLR4/NF-κB/HIF-1α-mediated glycolytic reprogramming. METHODS:Decidual tissues from PE patients and gestational age-matched healthy controls were analyzed by immunofluorescence, Western blot, qRT-PCR, Seahorse metabolic analysis, and ELISA. siRNA-mediated α7nAChR knockdown in THP-1-derived macrophages followed by LPS/IFN-γ stimulation was used to establish causality. Pharmacological inhibitors targeting TLR4, NF-κB, HIF-1α, or glycolysis were employed for pathway validation. Trophoblast function was assessed using macrophage-trophoblast co-culture systems. RESULTS:α7nAChR expression was significantly reduced in PE decidual macrophages and negatively correlated with TLR4, phosphorylated NF-κB, and HIF-1α levels. PE decidual macrophages exhibited enhanced M1 polarization, increased glycolytic enzyme expression, elevated extracellular acidification rate and pro-inflammatory cytokine secretion, with suppressed oxidative phosphorylation. In vitro, α7nAChR knockdown amplified LPS/IFN-γ-induced TLR4/NF-κB/HIF-1α signaling, glycolytic metabolism, and M1 polarization. These effects were attenuated by all four pathway inhibitors, confirming the hierarchical signaling cascade. Functionally, α7nAChR-deficient inflammatory macrophages induced trophoblast apoptosis and impaired invasion, both rescued by pathway inhibition. DISCUSSION:α7nAChR deficiency amplifies inflammatory stimuli-induced decidual macrophage M1 polarization through TLR4/NF-κB/HIF-1α-dependent glycolytic reprogramming, linking cholinergic anti-inflammatory pathway dysfunction to immunometabolic dysregulation at the maternal-fetal interface in PE. Targeting macrophage metabolic reprogramming may represent a potential therapeutic strategy for PE.

Cervical remodeling (CR) is essential for pregnancy maintenance and successful parturition, yet its molecular regulation in humans remains incompletely defined. This study aimed to present a high-resolution, longitudinal proteomic atlas of the human CR across normal gestation. A retrospective study was conducted using cervical tissue samples collected during nonpregnancy and at three trimesters. The study cohort included 10 healthy controls and 31 pregnant women with uncomplicated singleton pregnancies. Proteomic analyses were performed using data-independent acquisition mass spectrometry. Then, we carried out comparative proteomic analyses across adjacent gestational stages and unsupervised clustering of all quantified proteins based on their expression dynamics. Subsequently, we systematically characterized the dynamic regulation of collagen. Finally, protein-protein interaction networks based on temporally regulated proteins were constructed. We quantified 6092 proteins, revealing stage-specific shifts in immune regulation, extracellular matrix remodeling, and hormone responsiveness. Systematic evaluation of five canonical hypotheses for functional progesterone withdrawal identified receptor downregulation and hormone-binding protein sequestration as the dominant mechanisms within cervical tissue. Collagen composition and organization were progressively disrupted, accompanied by coordinated remodeling of hyaluronan, enzymatic expression levels, and elastic fiber components. Network-based analyses uncovered modular regulatory architectures and stage-specific rewiring of protein interactions. Finally, we infer fibronectin 1 (FN1), matrix-metalloproteases 9 (MMP9), and estrogen receptor 1 (ESR1) protein as central regulator molecules for CR. Our study provides a temporal framework to dissect stage-specific molecular events that drive CR. These findings establish a comprehensive proteomic framework for understanding human CR and highlight novel targets for predicting and modulating CR disorders.

External cephalic version (ECV) corrects breech presentation and improves vaginal delivery success rate. To investigate factors influencing ECV success in breech-presenting pregnant women in southern China. A total of 484 pregnant women who underwent ECV from August 2021 to August 2023 were enrolled. Logistic regression analyzed factors associated with ECV success, and restricted cubic spline (RCS) evaluated relationships of amniotic fluid index (AFI) and gestational weight gain with ECV success. In all ECV, the success rate was 75.41

Background Iodine is an essential trace element for pregnant women, and iodine deficiency was still reported in some areas worldwide. Shenzhen is located in southern China where is a coastal city and an iodine sufficient urban area, but there are not large-scale studies related to iodine nutrition status and thyroid function currently. Objectives The aims of our present study were to analyse the iodine nutrition status, and explore the potential associations between UIC and thyroid function during the first trimester of pregnancy in southern China. Methods In this cohort study, 14327 pregnant women during the first trimester were enrolled. Urinary Iodine Concentration (UI), Thyroid-Stimulating Hormone (TSH), Free Thyroxine (fT4), and Thyroid Peroxidase Antibody (TPOAb) were measured. The associations between thyroid function and Iodine nutrition status were estimated. Results The median UIC during the first trimester was 173.5 (118.2-247.5) µg/L, deficiency iodine status was observed in 39.3%. The UIC was negatively associated with TPO ( r= -0.034, P = 0.000). Thyroid dysfunction incidence was 32.97%, Autoimmune Thyroid Disease is the most prevalent one (52.48%). The participants with Thyroid Dysfunction showed higher age ( t= -3.856, P = 0.000) and lower UIC ( χ 2 = 26.079, P = 0.000). ≥35 years old ( β = 0.102, P = 0.041, OR = 1.108,95% CI = 1.004–1.221), severe deficiency Iodine status ( β = 0.224, P = 0.007, OR = 1.251,95% CI = 1.062–1.473) and excess Iodine status ( β=- 0.430, P = 0.000, OR = 0.651,95% CI = 0.524–0.807) were the main determinants of thyroid dysfunction in our study cohort. Conclusions There were 39.3% incidence of deficiency iodine and 32.97% incidence of thyroid dysfunction in first trimester of pregnancy in southern China, where is an iodine sufficient urban area. The UIC was negatively associated with TPO. Higher age, severe deficiency and excess Iodine status were the main determinants of thyroid dysfunction. Additional studies of the Iodine nutrition status and dietary factors that can contribute to the prevention of thyroid dysfunction diseases in pregnant women living in iodine sufficient area are needed.

Physiological blood pressure changes in pregnancy are insufficiently defined. This paper describes the blood pressure changes across healthy pregnancies in a Southern Chinese population to present gestational - age - specific blood pressure ranges with smoothed centiles (3rd, 10th, 50th, 90th, and 97th). Antenatal blood pressure measurements [median (interquartile range) 9 (8 - 10) per woman] were repeated in 17, 776 women from a Southern China population. Multilevel cubic splines models were used to derive longitudinal reference ranges for systolic blood pressure (SBP) and diastolic blood pressure (DBP) from 6 to 42 weeks of gestation for the normal pregnancies (excluding chronic hypertension, preeclampsia, diabetic ones, and preterm birth et al.). Systolic and diastolic BP increased from 6 weeks of gestation: 50th centile (3rd - 97th centile) 106 (87 - 125); 61 (47 - 77) mm Hg to 12 weeks of gestation: 50th centile (3rd - 97th centile) 108 (88 - 129); 64 (49 - 81) mm Hg. Then, the lowest value of 107 (87 - 129); 62 (47 - 78) mm Hg was reached at 16 weeks and 20 weeks of gestation, respectively. Systolic and diastolic BP then rose to a maximum median (3rd - 97th centile) of 115 (96 - 135); 68 (53 - 85) mm Hg at 42 weeks of gestation. Additionally, the ascending tendency of SBP after 16 weeks of gestation was interrupted by two fluctuations that occurred at 24 weeks and 30 weeks of gestation. In summary, our study provides blood pressure reference values for Southern Chinese women with normal pregnancies. To identify gestational hypertension and hypotension, centiles for gestational - age - specific BP should be defined in healthy pregnancies. Understanding these changes in low risk pregnancies is essential to optimize maternal blood pressure management.

Endogenous estrogen and progesterone and their metabolites play a key role in regulating and maintaining the normal pregnancy process. However, the dynamic change of these estrogen and progesterone metabolites’ level across the entire gestational period is not fully revealed. This study systematically measures the temporal changes of estrogen, progesterone, and their metabolites in human urine during normal pregnancy using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We find that the levels of estrone, estradiol, estriol, 16-epiestriol, 17-epiestriol, 2-methoxyestradiol, and 4-hydroxyestrone gradually increase during pregnancy. The levels of 2-hydroxyestrone, 2-hydroxyestradiol, and 4-hydroxyestradiol rapidly decrease in the early pregnancy and then maintain at lower levels. The levels of 4-methoxyestradiol, 4-methoxyestrone and 2-methoxyestrone peak in the mid-pregnancy and then gradually decrease. The levels of pregnenolone, 17α-hydroxy pregnenolone, 17α-hydroxy progesterone, pregnanolone, epipregnanolone gradually increase during pregnancy. The levels of progesterone, 20α-hydroxy progesterone, 5α-dihydroprogesterone and 5β-dihydroprogesterone first increase in the mid pregnancy and then decrease in the late pregnancy. In sum, this study comprehensively depicts the dynamic change of estrogen, progesterone, and their metabolites in human urine during pregnancy, which lays the foundation for hormone monitoring and early diagnosis of pregnancy complications, and further mechanistic study of the roles of these metabolites in pregnancy.

Epstein-Barr virus (EBV) persistently infects more than 90% of the human population, causing infectious mononucleosis1, susceptibility to autoimmune diseases2 and multiple malignancies of epithelial or B cell-origin3. EBV infects epithelial cells and B cells through interaction between viral glycoproteins and different host receptors4, but it has remained unknown whether a common receptor mediates infection of its two major host cell targets. Here, we establish R9AP as a crucial EBV receptor for entry into epithelial and B cells. R9AP silencing or knockout, R9AP-derived peptide and R9AP monoclonal antibody each significantly inhibit, whereas R9AP overexpression promotes, EBV uptake into both cell types. R9AP binds directly to the EBV glycoprotein gH/gL complex to initiate gH/gL-gB-mediated membrane fusion. Notably, the interaction of R9AP with gH/gL is inhibited by the highly competitive gH/gL-neutralizing antibody AMMO1, which blocks EBV epithelial and B cell entry. Moreover, R9AP mediates viral and cellular membrane fusion in cooperation with EBV gp42-human leukocyte antigen class II or gH/gL-EPHA2 complexes in B cells or epithelial cells, respectively. We propose R9AP as the crucial common receptor of B cells and epithelial cells and a potential prophylactic and vaccine target for EBV.

Preterm birth (PTB) significantly contributes to maternal and perinatal mortality and lifelong morbidity. While large language models (LLM) offer considerable potential for disease risk prediction and early detection, their application to PTB prediction using multi-omics data remains limited. We developed a novel transformer-based architecture for integrating cell free (cfDNA) and cfRNA sequencing data for PTB risk prediction. In the test set, the cfDNA LLM model achieved an AUC of 0.822, and the cfRNA LLM model achieved 0.851. Integrating cfDNA and cfRNA data within the transformer-based framework outperformed both, reaching an AUC of 0.890, a significant improvement over single-modality models. Additionally, we explored cfRNA and cfDNA integration using RNA editing and achieved an AUC of 0.82. This underscores the potential of multi-omics data fusion, with transformer-based architectures providing a powerful framework for disease risk assessment, and demonstrates the potential of AI-driven multi-omics for broader applications in precision obstetrics and biomedicine.

This study has registered in National Medical Research Registration and Filing Information System of China ( www.medicalresearch.org.cn . Id: MR-44-25-004777).

Background:The study of 24-hour urinary total protein (24-h UTP) excretion is an essential parameter for the assessment of renal function and early detection of pregnancy complications. However, data on reference interval for 24-h UTP in women with twin pregnancies are scarce. Objective:We aimed to establish the reference interval for 24-h UTP excretion in women with twin pregnancies and compare it with that in women with singletons. Study Design:A total of 12,633 participants with singletons or twin pregnancies were recruited. They were instructed to collect standard 24-hour urinary samples. Information was extracted from the electronic medical record. The nonparametric percentile method was used to determine reference interval for 24-h UTP excretion during different trimesters in women (excluding, among others, those with preexisting renal disease, gestational or chronic hypertension, pre-eclampsia, and pregestational diabetes mellitus). Results:In twin pregnancies, the 24-h UTP levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 74.2 (32.7, 195.5) mg, 104.5 (41.9, 213.1) mg, and 152.6 (46.1, 415.7) mg in the first, second, and third trimesters, respectively. A significant increase in 24-h UTP excretion was observed throughout pregnancy (all P<.001). Furthermore, the median (25th, 75th) of 24-h UTP values in the singleton group and twin groups were 70.2 (48.5, 98.3) vs 74.2 (47.3, 108.2) mg, 84.8 (58.5, 118.2) vs 104.5 (78.4, 135.6) mg, and 108.0 (73.4, 149.3) vs 152.6 (90.8, 192.8) mg in the first, second, and third trimesters, respectively. (Part of the data on singleton pregnancy has previously been published). The 24-h UTP excretion in the twin group was significantly higher than those in the singleton group in the second and third trimesters (both P<.001). Conclusion:Physiological proteinuria levels were approximately doubled in late pregnancy in women with twin pregnancies compared to early pregnancy, and the upper limit of normal 24-h UTP excretion is 415.7 mg in late pregnancy. Moreover, the threshold for elevated proteinuria in twin pregnancies could be higher than in singletons from the second trimester onwards. Understanding these changes is essential for precise twin management and patient counseling.

BACKGROUND:Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear.METHODS:Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based studies and animal models including conditional knockout mice and a new preeclampsia mouse model induced by recombinant mouse galectin-9 were applied to validate the pathogenic role of a CD11chigh subpopulation of decidual macrophages (dMφ) and to determine its underlying regulatory mechanisms in preeclampsia. A retrospective preeclampsia cohort study was performed to determine the value of circulating galectin-9 in predicting preeclampsia.RESULTS:We discovered a distinct CD11chigh dMφ subset that inhibits spiral artery remodeling in preeclampsia. The proinflammatory CD11chigh dMφ exhibits perivascular enrichment in the decidua from patients with preeclampsia. We also showed that trophoblast-derived galectin-9 activates CD11chigh dMφ by means of CD44 binding to suppress spiral artery remodeling. In 3 independent preeclampsia mouse models, placental and plasma galectin-9 levels were elevated. Galectin-9 administration in mice induces preeclampsia-like phenotypes with increased CD11chigh dMφ and defective spiral arteries, whereas galectin-9 blockade or macrophage-specific CD44 deletion prevents such phenotypes. In pregnant women, increased circulating galectin-9 levels in the first trimester and at 16 to 20 gestational weeks can predict subsequent preeclampsia onset.CONCLUSIONS:These findings highlight a key role of a distinct perivascular inflammatory CD11chigh dMφ subpopulation in the pathogenesis of preeclampsia. CD11chigh dMφ activated by increased galectin-9 from trophoblasts suppresses uterine spiral artery remodeling, contributing to preeclampsia. Increased circulating galectin-9 may be a biomarker for preeclampsia prediction and intervention.

Background: Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. Objective: This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. Study design: This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6(+0) to 13(+6), 14(+0) to 27(+6), and 28(+0) to 41(+6) weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). Results: The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (>= 35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). Conclusion: Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.

Objective The mechanism of cervical ripening in late pregnancy is still unclear. The vaginal microbiome has been reported to correlate with the preterm birth and short cervix in pregnant women. However, the associations between the cervical maturity and the vaginal microbiome are still poorly understood. We aim to analyze the cervicovaginal microflora in women with ripe cervix and in those who are unripe when delivering at term. Methods Cervicovaginal swabs were collected between 40 and 41 weeks of gestation from the following 2 different groups of patients: ripe group (n = 25) and unripe group (n = 25). Samples were tested using 16S ribosomal RNA gene high-throughput sequencing and analyzed by bioinformatics platform. Results This study highlights the relationship between cervical maturity during late pregnancy and the composition of the cervicovaginal microflora. Both α- and β-diversity analyses demonstrated significant differences between women with a ripe cervix and those with an unripe cervix. Notably, the Lactobacillus profile was found to be closely linked to cervical maturity. There was a significant difference in the vaginal community state type, with CST IV being more prevalent in women with an unripe cervix. Furthermore, the association between CST IV and the unripe cervix group, as indicated by the odds ratio of 8.6, underscores its relevance in evaluating cervical maturity, when compared to other Lactobacillus-dominant community state types. Additionally, several bacterial taxa, particularly Lactobacillus, exhibited differential relative abundances between the two groups. Conclusion This study provided significant evidence regarding the relationship between the vaginal microbiome and cervical maturity, highlighting the differential diversity, community state types, and specific bacterial taxa, such as Lactobacillus, that are associated with cervical maturation status. These findings contributed to our understanding of the dynamics of the cervicovaginal microflora during late pregnancy and its implications for cervical health.

Background White blood cell (WBC) count increases during pregnancy, necessitating reliable reference intervals for assessing infections and pregnancy-related complications. This study aimed to establish comprehensive reference intervals for WBC counts during pregnancy. Methods The analysis included 17,737 pregnant women, with weekly WBC count measurements from pre-pregnancy to postpartum. A threshold linear regression model determined reference intervals, while Harris and Boyd’s test partitioned the intervals. Results WBC count exhibited a significant increase during pregnancy, characterized by a rapid rise before 7 weeks of gestation, followed by a plateau. Neutrophils primarily drove this increase, showing a similar pattern. The threshold regression model and Harris and Boyd’s test supported partitioned reference intervals for WBC counts: 4.0–10.0 × 10^9/L for < = 2 weeks, 4.7–11.9 × 10^9/L for 3–5 weeks, and 5.7–14.4 × 10^9/L for > = 6 weeks of gestation. These reference intervals identified pregnant women with high WBC counts, who had a higher incidence of pregnancy-related complications including placenta previa, oligohydramnios, secondary uterine inertia, and intrauterine growth restriction. Conclusion This study establishes comprehensive reference intervals for WBC counts during pregnancy. Monitoring WBC counts is clinically relevant, as elevated levels are associated with an increased risk of infection and pregnancy-related complications.

BACKGROUND:Intravenous calcium administration has shown promise in enhancing uterine contractions and reducing blood loss during cesarean delivery, but this regimen has not been compared in vaginal labor induction. OBJECTIVE:This study aimed to determine the efficacy of oxytocin combined with calcium vs oxytocin alone for inducing labor in women with term premature rupture of membranes. STUDY DESIGN:This single-blind, randomized controlled trial was conducted between October 2022 and May 2023 at a tertiary university hospital. Patients diagnosed with premature rupture of membranes were randomly allocated into 2 groups. The intervention group received a bolus of 10 mL of calcium gluconate followed by a continuous infusion of oxytocin via a pump (n=210), whereas the control group received only oxytocin infusion (n=218). The primary outcome was successful vaginal deliveries within 24 hours after labor induction. The secondary outcomes included the interval from labor induction to delivery, vaginal delivery blood loss, and maternal and neonatal complications. RESULTS:Baseline characteristics, including maternal age, body mass index, and Bishop score before labor induction, were comparable between the groups. The rate of vaginal delivery within 24 hours after labor induction was statistically higher in the intervention group (79.52% vs 70.64%; P=.04). The participants in the intervention group experienced a shortened interval between labor induction and delivery (10.48 vs 11.25 hours; P=.037) and demonstrated a higher success rate in labor induction assessed by the onset of the active phase (93.80% vs 87.61%; P=.04) without increasing the cesarean delivery rate. Reduced hemorrhage was observed in the intervention group (242.5 vs 255.0 mL; P=.0015), and the maternal and neonatal outcomes were comparable between the groups. CONCLUSION:The coadministration of calcium and oxytocin in labor induction among pregnancies with premature rupture of membranes was more efficient and safer than the administration of oxytocin alone. Our research suggests that the combination therapy of calcium and oxytocin may offer significant advantages during the process of labor induction and result in better outcomes. VIDEO ABSTRACT.

Preterm birth (PTB), a leading cause of neonatal mortality, presents challenges in prediction with current methods focusing on traditional risk factors or biomarkers, particularly for spontaneous preterm birth (sPTB). Here, we developed a machine-learning framework based on untargeted cervicovaginal fluid proteomics from 707 individuals (136 sPTB and 571 FTB, Full-term birth) across five hospitals. Our analysis identified 293 proteins with potential predictive value, subsequently distilled into a robust predictive model composed of five protein markers (LUM, AMBP, B2M, FN1, and TIMP1) demonstrating outstanding performance in predicting the risk of sPTB. It achieved area under the receiver operating characteristic curve values of 0.89, 0.90, 0.92, and 0.94 in independent validation datasets from four hospitals, with an overall sensitivity = 0.73 and specificity = 0.92. Moreover, we reproduced the predictive performance of these five biomarkers using enzyme-linked immunosorbent assay (ELISA). At system level, integrating proteomics data from all hospitals, we delineated two distinct molecular subtypes of sPTB, revealing functional differences. Concurrently, we conducted a drug target analysis, unveiling potential preventative drugs for sPTB. In summary, this research expands the repertoire of sPTB prediction biomarkers, offers a novel non-invasive predictive model for sPTB and provides valuable data resources for further investigation into the pathogenesis of preterm birth.

Background Krüppel-like factor 15 (KLF15) has been reported to be involved in ischemia injury of multiple types of diseases. Nevertheless, the roles and underlying mechanisms of KLF15 in preeclampsia (PE) are still unclear. Methods In this study, the expression of KLF15 in placenta tissues and hypoxia/reoxygenation (H/R)-induced HTR8/SVneo cells was evaluated by GSE66273 database, qRT-PCR and western blot assay. CCK-8 assay was employed to detect cell proliferation. Wound healing assay and transwell assay were used to detect cell migration and invasion. Celloxidative stress was measured by DCFH-DA staining and kits. Cell apoptosis was evaluated by TUNEL assay and western blot assay. The JASPAR database was used to analyze the binding site of KLF15 and insulin-like growth factor-1 receptor (IGF1R) promoter region. The luciferase reporter assay was used to detect IGF1R promoter activity and ChIP assay was used to verify the combination of KLF15 and IGF1R promoter. Moreover, western blot was employed to measure the expressions of PI3K/Akt-related proteins. Results The data showed that the expression of KLF15 was significantly downregulated in GSE66273 database, tissues and HTR8/SVneo cells. KLF15 overexpression increased H/R-induced HTR8/SVneo cell proliferation, invasion and migration, and inhibited oxidative stress and cell apoptosis. In addition, IGF1R was highly expressed in H/R-induced HTR8/SVneo cells after KLF15 overexpression, and the binding of KLF15 and IGF1R promoter was verified. Silencing of IGF1R reversed the effects of KLF15 overexpression on H/R-induced HTR8/SVneo cell proliferation, migration, invasion, oxidative stress and cell apoptosis. Moreover, KLF15 overexpression and IGF1R silencing regulated the expressions of PI3K/Akt-related proteins in H/R-induced HTR8/SVneo cells. Conclusion In conclusion, KLF15 overexpression promoted the proliferation and metastasis, and suppressed oxidative stress and cell apoptosis of H/R-induced HTR8/SVneo cells through mediating the PI3K/Akt pathway, which may provide a promising target for the treatment of preeclampsia.

PurposePreeclampsia/Eclampsia (PE/E) poses significant risks to neonatal cardiac health. Traditional echocardiographic methods have limitations in detailing these impacts. This study hypothesized that echocardiographic radiomics could provide a more comprehensive assessment of the cardiac changes in neonates affected by PE/E.MethodIn a comprehensive analysis, 2594 neonates underwent echocardiographic screening. From these, 556 were selected for detailed radiomics analysis, focusing on cardiac shape, movement, and texture features. A multiblock sparse partial least squares (sPLS) model integrated these features to assess their association with PE/E.ResultsNewborns from PE/E-affected pregnancies displayed lower left ventricular ejection fractions compared to the control group (61.1 % vs. 66.2 %). Our radiomics approach extracted 15,494 features per neonate, with the sPLS model identifying 17 features significantly correlated with PE/E. Among these, texture features representing myocardial non-compaction were most strongly correlated with PE/E (correlation coefficient r = 0.63). Detailed visualization of these texture features suggested that PE/E might lead to more pronounced myocardial non-compaction, characterized by a thicker non-compaction layer and increased cardiac trabeculation.ConclusionsOur findings demonstrate the potential of echocardiographic radiomics as a tool for assessing the impact of PE/E on neonatal cardiac function. The correlation between PE/E and myocardial non-compaction underlines the need for enhanced cardiac monitoring in neonates born to PE/E-affected mothers. This study contributes to a better understanding of PE/E's cardiac implications, potentially guiding future clinical practices.