OBJECTIVE:To characterize epidemiology, treatment efficacy, and prognosis in cervical cancer patients aged <25 years using SEER data and institutional validation, and propose personalized strategies. METHODS:We analyzed 73,869 SEER database patients (2000-2021), including 544 aged <25 years. Epidemiological trends, histology, and staging were assessed. Survival models compared 3-/5-year survival rates: surgical (n = 25) vs. non-surgical (n = 9) treatment for stage IB3; surgical (n = 18) vs. non-surgical (n = 4) for stage IIA2; and adjuvant chemotherapy (n = 51) vs. non-chemotherapy (n = 6) for stages IIIA-IIIB. Findings were validated against institutional data (n = 12; 2009-present). RESULTS:Among SEER Database, the proportion of young patients significantly declined from 1.36% (2004) to 0.39% (2021), with poorly differentiated carcinoma predominating (51.65%). Squamous cell carcinoma accounted for the majority (59.56%), rare histological subtypes accounted for (12.68%) including small cell neuroendocrine carcinoma and clear cell carcinoma, with notable prognostic implications. Most young patients presented with early-stage disease (77.94%, n = 298/424). For stage IB3, surgery yielded higher 3-year (84% vs 55.56%) and 5-year survival (80% vs 44.44%) than non-surgical management. Stage IIA2 comparisons showed conflicting trends (potentially due to small samples). In stages IIIA-IIIB, adjuvant chemotherapy was associated with trends toward improved survival, and cumulative risk analysis suggested a potential reduction in long-term mortality risk in the chemotherapy group versus non-chemotherapy. Institutional data mirrored SEER treatment patterns. Histologic subtype emerged as a critical prognostic determinant; Both institutional deaths occurred in patients with rare histologies (stage IVB small cell neuroendocrine carcinoma; stage IIB clear cell carcinoma), suggesting histology may represent an important prognostic factor, potentially interacting with stage. CONCLUSION:Most young cervical cancer patients present with early-stage, poorly differentiated disease. Surgery may be beneficial for early-stage (≤IIB) disease in selected patients localized disease, while concurrent chemoradiotherapy (CCRT) plus brachytherapy remains the standard for advanced stages (IIIA-IIIB); the role of Adjuvant chemotherapy did not demonstrate a significant survival benefit and should be interpreted with caution. Tumor histology may outweigh stage as a prognostic determinant in this population. These findings are exploratory and require validation in prospective studies.

The impact of late-pregnancy glycemic control on pregnancy outcomes, especially in women with normal oral glucose tolerance test (OGTT) in mid-pregnancy, remain unclear. This study aimed to explore the potential benefits of maintaining glycemic levels within the target range during late pregnancy for improving pregnancy outcomes. A prospective cohort study (2018–2022) categorized participants into four groups based on the results of OGTT in mid-pregnancy and late-pregnancy fasting blood glucose (FBG) level: (1) Persistent normoglycemic group (PNG): normal OGTT, FBG < 5.3 mmol/L; (2) Late-pregnancy isolated hyperglycemia group (LPIHG): normal OGTT, FBG ≥ 5.3 mmol/L; (3) Gestational diabetes mellitus (GDM) with target glycemic control group (GDM-TC): GDM diagnosis, FBG < 5.3 mmol/L; (4) GDM with suboptimal glycemic control group (GDM-SC): GDM diagnosis, FBG ≥ 5.3 mmol/L. Associations with adverse perinatal outcomes were assessed using multivariate logistic regressions and population attributable fractions (PAF). A total of 35,378 pregnant women were included. The average age and pre-pregnancy BMI of all participants were 32.04 ± 3.85 and 21.86 ± 3.34 kg/m2. Of the participants, 15.43

Ovarian cancer (OC) is the most lethal of gynecological cancers and presents a poor prognosis due to difficulty in early diagnosis, extensive abdominal metastasis and chemo-resistance. We utilized single-cell transcriptomics to deconvolute intratumoral heterogeneity and identify biomarkers and therapeutic targets. Single-cell RNA sequencing (scRNA-seq) were performed with 15 patient samples. Metastatic and chemo-resistant epithelial subclusters were discovered by copy-number variations (CNV), Kaplan–Meier and enrichment analysis. Fucosyltransferase 11 (FUT11) was identified by differential expression analysis and validated by in vitro assays. Cell-cell communication analysis and protein–protein interaction (PPI) network were conducted to discover pathways and receptors in FUT11 positive (FUT11+) cells. Function of FUT11 in transforming growth factor- β (TGF- β ) pathway and drug response prediction were analyzed. Epithelial subcluster EC5 was associated with metastasis, chemo-resistance and poor prognosis of OC. FUT11 was a hub gene of EC5 and communicated with mesenchymal cells through TGF- β receptors to regulate downstream genes. FUT11 could be applied in chemo-resistance prediction and drug discovery. The present research provided new insights into gene signatures for tumor progression and drug discovery, and identified FUT11 as a diagnostic biomarker and therapeutic target.

BACKGROUND:Maternal anaemia is a public health issue globally, associated with adverse maternal and neonatal outcomes. However, less is known about the effects of high haemoglobin (Hb) and haematocrit (Hct) on the risk of stillbirth. OBJECTIVES:We assessed the dose-response effects of dynamic changes in maternal Hb and Hct across all trimesters on stillbirth risk. METHODS:This study was based on the prospective, longitudinal, population-based China birth cohort study (CBCS) between 2018 and 2022, including 142,715 women with live births or stillbirths delivered at ≥ 20 weeks' gestation. The modified Poisson regression models were used to assess the association between Hb/Hct, haemodilution status across three trimesters and stillbirth. RESULTS:Over a fifth (23.6%) of pregnant women had anaemia at least once during pregnancy. Maternal anaemia increased the risk of stillbirth. The adjusted risk ratio (aRR) for Hb at 70-99 g/L (moderate anaemia) was 2.45, 95% confidence interval (CI) 1.26, 4.76 and aRR for Hct < 33% (anaemia) was 1.63 (95% CI 1.12, 2.38) in the first trimester. Interestingly, a U-shaped association between Hb/Hct and stillbirth was observed, and high Hb/Hct levels in any of the three trimesters were related to increased stillbirth risk. Excessive haemoglobin dilution/haemoglobin concentration across trimesters was also associated with higher stillbirth risk, especially from the first to the second trimesters, with aRRs of 1.86 (95% CI 1.15, 3.01) and 3.34 (95% CI 2.08, 5.37), respectively. CONCLUSIONS:Considering the U-shaped association between Hb/Hct levels and stillbirth, clinical vigilance is necessary at both low- and high-extremes of Hb/Hct and physiological haemodilution metrics in mid-to-late pregnancy for improved pregnancy outcomes.

BACKGROUND:The American Heart Association (AHA) has updated the definition of cardiovascular health (CVH) from "Life's Simple 7" (LS7) to "Life's Essential 8" (LE8). The association between gestational LE8 CVH status and adverse pregnancy outcomes is unclear. METHODS:We recruited pregnant women from the China birth cohort study during 6-13+6 gestation weeks and followed them up until delivery to identify pregnancy outcomes. According to the modified AHA definitions, baseline gestational modified LE8 (mLE8) and LS7 CVH scores were calculated based on body mass index, nicotine exposure, physical activity, diet, blood pressure, blood glucose, and lipid levels. Multivariable adjusted logistic regression and receiver operating characteristic (ROC) curves were used to investigate the association between gestational CVH and adverse pregnancy outcomes. RESULTS:Among the 5168 pregnant women finally included, the overall gestational mLE8 CVH score was 81.4 ± 9.6 points. After multivariate adjustment, each 10-points increase in the total overall gestational mLE8 CVH score was significantly associated with a decreased risk of pregnancy loss [odds ratio (OR) = 0.85, 95% CI: 0.76-0.95), hypertensive disorders of pregnancy (OR = 0.50, 95% CI: 0.44-0.58), gestational diabetes mellitus (GDM) (OR = 0.62, 95% CI: 0.57-0.67), preterm birth (OR = 0.76, 95% CI: 0.67-0.86), large-for-gestational age (LGA) (OR = 0.81, 95% CI: 0.73-0.90), and cesarean delivery (OR = 0.77, 95% CI: 0.72-0.82)]. The areas under the ROC curves (AUC) of mLE8 were higher than those of LS7 for pregnancy loss (0.553 vs. 0.537, p = 0.031), GDM (0.626 vs. 0.615, p = 0.023), LGA (0.575 vs. 0.557, p = 0.016), and cesarean delivery (0.574 vs. 0.564, p = 0.005). CONCLUSIONS:Higher gestational mLE8 CVH scores in the first trimester are significantly associated with a lower risk of adverse pregnancy outcomes. Although the capacity to predict adverse pregnancy outcomes was modest, mLE8 slightly outperformed LS7 in predicting PE, GDM, LGA, and cesarean delivery.

Abstract Background The tumor microenvironment plays a crucial role in determining the prognosis of tumors. Fc gamma receptor IIa (FcγRIIa), one of the three subtypes of FcγRII, is expressed on platelets and immunocytes such as macrophages and neutrophils. These cellular elements collectively contribute to the tumor microenvironment. Previous research has indicated that FcγRIIa activates platelets and inflammatory cells, thus participating in tumor growth and metastasis. Nonetheless, limited information is available regarding FcγRIIa levels in most cancer types. This study aimed to detect serum FcγRIIa in 333 patients with non-small cell lung cancer (NSCLC) and 100 healthy individuals, and to explore the relationship between serum FcγRIIa levels and clinical outcomes in patients with NSCLC. Methods Serum samples from 333 patients with stage I–IV NSCLC and 100 healthy volunteers were analyzed using ELISA. The clinical and laboratory data underwent statistical analysis. Results Circulating FcγRIIa levels were markedly increased in patients with NSCLC, especially in advanced pathologic stages.ROC curve analysis yielded an AUC of 0.7713 (95% CI: 0.7132–0.8264), with an optimal cutoff value of 2115.88 pg/mL based on the Youden index (sensitivity: 60.06%, specificity: 86.00%). Notably, 13% of healthy controls showed FcγRIIa levels above the cutoff, suggesting that elevated FcγRIIa may partially reflect systemic inflammatory status. Survival analysis in 333 patients with NSCLC showed markedly shorter overall survival in FcγRIIa-positive cases. Serum FcγRIIa levels were further identified to be significantly associated with metastatic status. Conclusion This study demonstrated that circulating FcγRIIa levels rise along with tumor progression and may serve as a potential complementary prognostic indicator in metastatic NSCLC, though these findings require validation in prospective cohorts with comprehensive adjustment for inflammatory markers and treatment regimens.

Abstract High-grade serous ovarian carcinoma (HGSOC) is an aggressive malignancy marked by high recurrence rates, poor prognosis, and limited response to immune checkpoint inhibitors, primarily attributable to its immunologically “cold” tumor microenvironment (TME). To profile the immunological landscape of HGSOC, we conducted single-cell RNA sequencing (scRNA-seq) on 84,065 cells from tumor tissues of eight treatment-naïve patients and one normal ovarian tissue, identifying six major cell clusters and revealing substantial immune cell infiltration. Further analysis of CD8⁺ T cells identified two key subpopulations—precursor and terminally exhausted T cells—and delineated their developmental trajectories. The accumulation of exhausted CD8⁺ T cells (Tex) suggested an immunosuppressive TME. Integrated trajectory inference and high-dimensional weighted gene co-expression network analysis (hdWGCNA) identified CCL3 as a novel hub gene specifically expressed in Tex cells. Communication analysis suggested that Tex cells may interact with M2 macrophages via the CCL3–CCR1 ligand–receptor axis. Functional validation confirmed that: (1) secretomes from Tex cells—but not effector T cells—significantly promoted M2 polarization in both THP-1 and bone marrow-derived macrophages (CD206⁺ THP-1: 83.8% vs. 51.4%, p < 0.001; CD206⁺ BMDM: 72.4% vs. 41.5%, p < 0.001); and (2) recombinant CCL3 acted synergistically with IL-4/IL-10 to further enhance M2 polarization (59.2% vs. 37.7%, p = 0.008). Collectively, our findings unveil a previously unrecognized immunoregulatory axis whereby exhausted CD8⁺ T cells drive immunosuppression via CCL3–CCR1–mediated communication with M2 macrophages, presenting a promising therapeutic target to reverse the immune-cold TME in HGSOC.

Background Birth defects, which comprise a series of severe congenital abnormalities, impose a significant burden on society, families and individuals. Consequently, it is crucial to identify the underlying causes of birth defects and reduce their occurrence. Although an increasing number of risk factors for birth defects have been identified, few associations can be established as causal. Furthermore, the distribution of aetiology related to birth defects remains unclear. This study aims to analyse birth defect cases from the China Birth Cohort Study (CBCS) to elucidate the aetiological profile of these conditions.Methods A total of 3873 abnormal cases were recorded in the CBCS from November 2017 to August 2021. Abnormal fetuses (including both live births and foetal losses) were diagnosed by obstetricians, ultrasound specialists and geneticists based on prenatal screening and clinical examinations. The causes of birth defects were categorised into chromosomal anomalies, genetic anomalies, environmental exposures and twinning. Chromosomal and genetic anomalies were identified through genetic screening. Data on exposure, including the substances involved and the duration of exposure, were reviewed to determine whether environmental factors contributed to the birth defects.Results After excluding cases with minor malformations, a total of 2123 birth defect cases were reviewed. The most common birth defects among the included cases were congenital heart disease, polydactyly, trisomy 21 and cleft palate with cleft lip. Of these, only 22.4% (475/2123) had identifiable causes. Specifically, 415 cases were attributed to chromosomal anomalies, while 31 cases were diagnosed as monogenic disorders. Additionally, 23 cases were linked to environmental exposures, and 6 cases were associated with twinning. The proportions of birth defect cases with known causes were significantly higher in the spontaneous abortion group (12/27, 44.4%), the therapeutic abortion group (314/1044, 30.1%) and perinatal death group (13/36, 36.1%) compared with live births (136/1016, 13.4%).Conclusions Nearly 80% of birth defect cases in the CBCS lack a clear identifiable cause. Therefore, translating statistical associations between risk factors and birth defects into causal relationships is both necessary and important.

ObjectiveTo evaluate the efficacy and safety of the Peiyu Granules (PYG) compared with placebo on early miscarriage rates among women undergoing embryo transfer.MethodsA double-blind, parallel-group randomized clinical trial between February 15, 2017, and June 17, 2019, within 10 months of pregnancy follow-up until March 2020. This clinical trial was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. A total of 886 women were included in this study. The intervention group (n = 443) received PYG on the night of Embryo Transfer (ET) until the day of the hCG test. If it was negative, the patient stopped taking medicine. In contrast, the treatment continued until 70 days after ET. The women in the control group (n = 443) consumed the same amount of placebo as the intervention group. All women enrolled were subject to the same follow-up protocols. The primary outcome was early miscarriage rate. The secondary outcomes were clinical intrauterine pregnancy rate and live birth rate.ResultsAmong the 886 randomized women (mean [SD] age, 32.8 [3.6] years), 854 women (96.4%) underwent ET and followed the treatment of random grouping. Early miscarriage occurred among 17 of 133 women (12.8%) receiving PYG compared with 35 of 156 women (22.4%) receiving placebo (relative risk[RR], 0.51 [95% CI, 0.27 to 0.95], P = 0.02). Clinical intrauterine pregnancy rates were 30.0% (133 of 443) in the intervention group and 35.2% (156 of 443) in the control group (relative risk[RR], 0.79 [95% CI, 0.60 to 1.05], P = 0.10). Live-birth rates were 25.3% (112 of 443) in the intervention group and 25.7% (114 of 443) in the control group (relative risk[RR], 0.98 [95% CI, 0.72 to 1.32], P = 0.88). Live birth rates in the clinical pregnant population were 84.2% (112/133) in the intervention group and 73.7% (115/156) in the control group (relative risk [RR], 1.14 [95% CI, 1.01 to 1.29], P = 0.03).ConclusionThe findings suggested that PYG reduced early miscarriage rates among women undergoing embryo transfer. However, there were no significant improvement in clinical pregnancy rates and live birth rates.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=12343 identifier, ChiCTR-inr-16010087.

Chemoresistance, the primary cause of mortality among ovarian cancer (OC) patients, is a multifaceted process encompassing numerous biological phenomena. As sequencing technology continues to advance, single-cell sequencing has surfaced as a potent strategy to elucidate the pathogenesis of OC. We examined single-cell sequencing data derived from five OC samples (three resistant and two sensitive) and identified an epithelial subcluster associated with chemotherapy resistance and poor prognosis. Using GSVA and cell communication analysis, we explored the unique biological functions and communication characteristics of this resistant subcluster. We performed high dimensional weighted gene co-expression network analysis and differential expression analysis to identify the hub genes of c3. Lastly, we investigated the correlation between the hub gene, CLIC3, and chemotherapy drug sensitivity. We also validated their involvement in specific pathways using TCGA data. The effects and primary mechanism to chemoresistance of CLIC3 was explored. We identified a cell subcluster, denoted as c3, strongly linked to chemoresistance and poor prognosis in OC. This subcluster demonstrated a correlation with both extracellular matrix (ECM) formation and angiogenesis signature, with CLIC3 identified as its key marker. The expression levels of CLIC3 exhibit a significant association with the sensitivity to various chemotherapeutic drugs in OC. Mechanistically, CLIC3 increases OC resistance to cisplatin by promoting integrin β1 redistribution and PI3K-AKT pathway. This study offers a novel insight into the progression and chemoresistance of OC. Additionally, we identified a specific cell cluster highly associated with chemoresistance. The marker for this cluster, CLIC3, increases OC resistance to cisplatin by promoting integrin β1 redistribution and PI3K-AKT pathway and holds significant potential as a new therapeutic target for OC.

Given the maternal hypercoagulability during pregnancy, thrombophilia may increase the risk of adverse pregnancy outcomes (APOs). This retrospective case-control study aimed to assess whether low-molecular-weight heparin (LMWH) could improve APOs in women with protein S (PS) deficiency. We selected 35 pregnant women who were considered for potential PS deficiency, and 70 healthy pregnant women were randomly selected as the control group. Two or more consecutive miscarriages were more frequent in pregnant women with PS deficiency than in the control group (12/35 vs. 4/70, P = 0.0001). Ten pregnant women with PS deficiency conceived by in vitro fertilization-embryo transfer (IVF-ET), which was significantly higher than the number of controls who conceived by IVF-ET (4/70, P = 0.0012). All 20 women in the LMWH-treated group (P = 0.001) had live births, which were significantly higher than that in the LMWH-untreated group (8/15, 53.3

High-grade serous ovarian cancer (HGSOC) is an aggressive gynecological malignancy marked by widespread metastasis, most notably to the omentum. However, the molecular mechanisms driving this process remain poorly understood. We present an integrated analysis of single-cell RNA sequencing (scRNA-seq) data from normal ovaries, primary tumors, and omental metastases to generate a high-resolution cellular landscape of HGSOC. LAPTM5 expression was examined by immunohistochemistry, immunofluorescence, qPCR, western blotting, and analyses of TCGA datasets. Functional assays including Transwell migration/invasion, wound healing, flow cytometry, single-nucleotide variant (SNV) and alternative splicing (AS) analysis were performed after LAPTM5 knockdown. The proteins expression involved in epithelial-mesenchymal transition (EMT) and TGF-β mediated signaling pathways was verified by qPCR and western blotting. The critical role of LAPTM5 on metastasis in vivo was detected by the tumor-bearing mice model. We identified a metastasis-associated epithelial subcluster characterized by immune suppression and poor prognosis, with LAPTM5 emerging as a defining marker. Functional assays revealed that LAPTM5 silencing significantly impaired HGSOC cell migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, and reduced metastatic burden in vivo. Mechanistically, LAPTM5 activates the TGF-β/Smad signaling pathway, promoting EMT and facilitating omental metastasis. Intriguingly, LAPTM5 knockdown led to reduced single-nucleotide variant (SNV) accumulation and alternative splicing (AS) events, thereby decreasing the expression of metastasis-associated genes. These findings identify LAPTM5 as a key regulator of TGF-β/Smad-driven epithelial plasticity and omental dissemination in HGSOC, positioning it as both a prognostic biomarker and a potential therapeutic target for advanced-stage disease.

Objective:To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. Methods:A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. Results:A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. Conclusion:The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.

High-throughput sequencing technologies generate a vast number of DNA sequence reads simultaneously, which are subsequently analysed using the information contained within these fragmented reads. The assessment of sequencing technology relies on information efficiency, which measures the amount of information entropy produced per sequencing reaction cycle. Here we propose a fuzzy sequencing strategy that exhibits information efficiency more than twice that of currently prevailing cyclic reversible terminator sequencing methods. To validate our approach, we develop a fully functional and high-throughput fuzzy sequencer. This sequencer implements an efficient fluorogenic sequencing-by-synthesis chemistry and we test it across various application scenarios, including copy-number variation detection, non-invasive prenatal testing, transcriptome profiling, mutation genotyping and metagenomic profiling. Our findings demonstrate that the fuzzy sequencing strategy outperforms existing methods in terms of information efficiency and delivers accurate resequencing results with faster turnaround times.

BACKGROUND:This study aims to evaluate the association between maternal hepatic steatosis index (HSI) in the first trimester and adverse perinatal outcomes. METHODS:A prospective birth cohort study was conducted from 19 February 2018 to 31 December 2022 in China. Logistic regression models and restricted cubic splines were used to estimate the associations of maternal HSI in early pregnancy and the risk of perinatal outcomes. Subgroup analyses stratified by maternal age and gravidity were carried out. RESULTS:A total of 42,589 participants were included in this study. The overall prevalence of caesarean delivery, preterm birth, large-for-gestational age (LGA), shoulder dystocia and low Apgar scores were 39.17%, 5.18%, 9.45%, 0.92% and 0.77%, respectively. With the increase of HSI quartiles, the incidence of caesarean delivery, preterm birth, large-for-gestational age (LGA) and shoulder dystocia significantly increased (P < 0.0001). The highest quartile of HSI was associated with the highest risk of caesarean delivery (odds ratio (OR) 1.777, 95% CI 1.674-1.886), preterm birth (OR 1.323, 95% CI 1.160-1.510), LGA (OR 2.743, 95% CI 2.468-3.049) and shoulder dystocia (OR 1.487, 95% CI 1.094-2.021). The associations between HSI and adverse perinatal outcomes showed non-linear relationships except for shoulder dystocia (P < 0.0001 for all, P = 0.4792 for non-linearity). Subgroup analyses revealed that the associations between HSI and the risks of LGA and caesarean delivery were significantly stronger in younger and first-time pregnant women. CONCLUSION:Elevated maternal HSI in early pregnancy was positively associated with the risk of adverse perinatal outcomes.

Context: Previous studies have reported that pregnant women with non-alcoholic fatty liver disease (NAFLD) face an increased risk of gestational hypertension (GH) and preeclampsia (PE). However, no study has assessed the relationship between the Hepatic Steatosis Index (HSI), a biomarker for NAFLD, in early pregnancy and the subsequent risk of GH and PE. Objective: We aimed to investigate the relationship between HSI in early pregnancy and the risks of GH and PE in Chinese women. Methods: Based on the China Birth Cohort Study conducted from February 2018 to December 2022, this prospective cohort study collected liver enzyme and body mass index data from pregnant participants during 6-13+6 gestational weeks. The incidences of GH and PE were monitored until delivery. Results: This study included 39,114 pregnant women, and GH and PE incidences were 4.2% and 4.1%, respectively. After multivariable adjustment, the risks of GH (Q2: OR = 1.35, 95% CI = 1.13-1.62; Q3: OR = 1.86, 95% CI = 1.57-2.20; Q4: OR = 3.81, 95% CI = 3.25-4.46) and PE (Q2: OR = 1.22, 95% CI = 1.01-1.47; Q3: OR = 1.96, 95% CI = 1.65-2.32; Q4: OR = 3.60, 95% CI = 3.07-4.22) significantly increased with higher HSI quartiles. Further analysis indicated that compared to women aged 35 years or older, HSI in pregnant women under 35 years had relatively stronger predictive value for GH (OR ≥ 35 = 4.527, 95% CI = 3.762-5.446 vs. OR < 35 = 2.325, 95% CI = 1.729-3.128) and PE (OR ≥ 35 = 4.13, 95% CI = 3.433-4.983 vs. OR < 35 = 2.348, 95% CI = 1.736-3.176). Conclusion: Elevated HSI may be associated with an increased risk of GH and PE.

Tumor-associated macrophages (TAMs) play a pivotal role in immune suppression, tumor progression, and metastasis within the tumor microenvironment (TME) of ovarian cancer. While TAMs are known to promote T-cell dysfunction, the precise molecular mechanisms governing this process remain poorly understood. Here, we performed an integrated analysis of six high-grade serous ovarian cancer (HGSOC) single-cell sequencing datasets to investigate the molecular and functional diversity of TAMs in HGSOC. We identified an SPP1+ TAM subpopulation enriched in HGSOC and strongly associated with poor prognosis. These macrophages promoted T-cell exhaustion via the SPP1-CD44 axis, which emerged as the principal mediator of immune suppression. Functional assays demonstrated that SPP1 secreted by TAMs drove T-cell exhaustion, weakening anti-tumor immunity. Blocking either SPP1 or CD44 effectively reversed T-cell exhaustion, restored CD8+ T-cell functionality, and suppressed tumor growth in vivo. Furthermore, molecular docking and dynamics simulations identified nilotinib as a potential SPP1 inhibitor, exhibiting strong binding affinity and stability. In vitro assays confirmed that nilotinib reduced PD-1 expression in Jurkat cells induced by M2-type macrophages, underscoring its therapeutic potential in reversing T-cell exhaustion in ovarian cancer. The research demonstrates that SPP1+ TAMs drive immune suppression and T-cell exhaustion in ovarian cancer via the SPP1-CD44 axis, highlighting this pathway as a promising therapeutic target for reprogramming the immune microenvironment and improving patient outcomes.

Background The relationship of serum ferritin levels with the risk of gestational diabetes mellitus (GDM) remains unclear. The aim of this study is to investigate the association between serum ferritin levels and its change with the incident of GDM. Methods A prospective cohort study of 10,871 pregnancies from the China Birth Cohort Study were performed. Serum ferritin levels were measured by direct chemiluminescent method in the first and second trimester. Baseline serum ferritin were categorized into five groups by their quintiles in the first trimester. Serum ferritin changes were divided into four subgroups using the trimester-specific median as cut-off points. GDM was determined by a 75g oral glucose tolerance test at 24–28 weeks of gestation. Multivariate modified Poisson regressions were performed to estimate the independent relationship between serum ferritin levels and its change with the incident GDM. Results The median of serum ferritin levels in the first trimester was 57.7 ng/mL, and 13.5% of subjects developed GDM. After multivariate adjustment, the RRs and 95% CIs for incident GDM across baseline serum ferritin quintiles were 1.099 (0.940–1.285), 1.228 (1.055–1.430), 1.186 (1.018–1.383) and 1.179 (1.017–1.367), respectively. Furthermore, subjects with low serum ferritin levels in the first trimester but increased to high level in the second trimester (RR = 1.376,95%CI:1.169–1.612), as well as subjects with consistently high serum ferritin levels in the first and second trimester (RR = 1.351,95%CI:1.185–1.541) had a significantly increased risk of GDM. Conclusions Serum ferritin and its changes were independent risk factors of GDM. These findings underscore the importance of keeping iron metabolism at an appropriate level during early to middle pregnancy to reduce the risk of developing GDM.

Background: The relationship between maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) status and hypertensive disorders of pregnancy (HDP) remains uncertain. Methods: This was a prospective cohort study based on the China Birth Cohort Study (CBCS). 36,256 women were included at 6 to 13+6 gestation from February 2018 to December 2020. Generalized linear mixed models were used to investigate the association between thyroid function and HDP/BP. We further performed multiple subgroup analyses to test the robustness of this association. Results: The final study population was 25,608, and the overall incidence of HDP was 8.0%. After adjusting for maternal age, pre-pregnancy BMI, education, household annual income, smoking status, conception method and parity, the odds of HDP increased by 3.0% with a 1-unit increase in TSH (OR 1.03, 95% CI 1.04-1.06). Maternal TSH and TPOAb positivity were associated with a higher risk of preeclampsia or eclampsia but not gestational hypertension (TSH: OR 1.04, 95% CI 1.01-1.07; TPOAb positivity: OR 1.30, 95% CI 1.09-1.56). TSH and TPOAb positivity were significantly and positively associated with systolic pressure (TSH: β 0.02, 95% CI 0.07-0.26; TPOAb positivity: β 0.02, 95% CI 0.12-0.98) and diastolic pressure (TSH: β 0.02, 95% CI 0.02-0.17; TPOAb positivity: β 0.02, 95% CI 0.06-0.75). Subgroup analyses suggested that the association between TSH and diastolic pressure was stronger in those with BMI ≥ 25 kg/m2 (P = 0.014). Conclusions: Our founds suggest that high TSH and TPOAb positivity in the first trimester are associated with an increased risk of preeclampsia or eclampsia.

CONTEXT:Previous studies on the relationship between thyroid gland function and the development of gestational diabetes mellitus (GDM) have reported different results, leading to the need for a cohort study design with a large sample size. OBJECTIVE:We aimed to investigate the relationship between thyroid function in early pregnancy and GDM. METHODS:This was a prospective cohort study based on the China Birth Cohort Study (CBCS), from February 2018 to December 2020. The study took place at a tertiary maternal and child health hospital. A total of 36 256 pregnant women were successfully recruited based on the CBCS. The main outcome measure was GDM. RESULTS:This study consisted of 26 742 pregnant women who met the inclusion criteria, of whom 3985 (14.90%) were diagnosed with GDM, and the women with GDM were older than their healthy counterparts (33.26 ± 4.01 vs 31.51 ± 3.76 years, P < .001). After removing potential influencing variables, we found that increased thyroid-stimulating hormone (TSH) (adjusted odds ratio [aOR] 1.030, 95% CI 1.007, 1.054, P = .012) and subclinical hypothyroidism (aOR 1.211, 95% CI 1.010, 1.451, P = .039), but not free thyroxine or thyroid peroxidase antibody, were associated with the occurrence of GDM. Further analysis indicated a nonlinear relationship between TSH and GDM (P < .05): when TSH ≤ 1.24 mIU/L, the occurrence of GDM was elevated with increasing TSH, but when TSH > 1.24 mIU/L, this trend was not obvious. CONCLUSION:High TSH might be associated with increased risk of GDM.