Wentao Yue

1. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide [1]. Unfortunately, contrary to CVD mortality declines in the general population, the rate in women aged <55 ...

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: 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.

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.

High-grade serous ovarian cancer (HGSOC) is an aggressive gynecological malignancy marked by widespread metastasis, most notably to the omentum. However, t

Background 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. Methods 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. Results 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. Conclusions 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.

The relationship between serum ferritin levels and the risk of gestational diabetes mellitus (GDM) remains unclear. This study aimed to investigate the association between serum ferritin levels and the incidence of GDM. We conducted a prospective cohort study involving 10,871 pregnant women from the China Birth Cohort Study. Serum ferritin levels were measured using the direct chemiluminescence method in the first and second trimesters. Baseline serum ferritin levels were categorized into five groups according to quintiles in the first trimester, and trimester-specific median values were used to divide serum ferritin levels into four subgroups. GDM was determined by a 75 g oral glucose tolerance test at 24–28 weeks of gestation. Multivariate modified Poisson regression was performed to estimate the independent relationship between serum ferritin levels and the incident GDM. The median serum ferritin level in the first trimester was 57.7 ng/mL, and 13.5% of participants 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, participants with low serum ferritin levels in the first trimester that increased to high levels in the second trimester (RR = 1.376, 95% CI: 1.169–1.612) and those with consistently high serum ferritin levels in the first and second trimesters (RR = 1.351, 95% CI: 1.185–1.541) had a significantly increased risk of GDM. Changes in serum ferritin levels are independent risk factors for GDM. These findings underscore the importance of maintaining iron metabolism at an appropriate level during early to mid-pregnancy to reduce the risk of developing GDM.