To determine the role of inflammation-related proteins in predicting asthma severity and outcome, 92 inflammation-related proteins were measured in the asthmatic serum using Olink analysis. Different bioinformatics algorithms were developed to cross analyze with the single-cell or transcriptome data sets from the Gene Expression Omnibus database to explore the role of IL18R1 and related genes in asthma and idiopathic pulmonary fibrosis (IPF). Olink identified 52 differentially expressed proteins in asthma. They were strongly linked to the cytokine-cytokine receptor interaction, TNF, and NF-κB signaling pathway. Seven proteins were found in both single-cell RNA and Olink analyses. Among them, IL18R1 was predominantly expressed in mast cells, and the results suggested enhanced communication between mast cells and CD 8⁺ T cells. IL18R1 was upregulated in serum and induced sputum and bronchoalveolar lavage fluid of patients with uncontrolled or severe asthma. IL18R1 was positively correlated with TNFSF1 and OSM and S100A12. The diagnostic efficacy of these serum IL18R1-related molecules for asthma ranged from 0.839 to 0.921. Moreover, high levels of IL18R1, TNFSF1, OSM, and S100A12 were significantly associated with shorter survival times and worse lung function. IL18R1-related molecules may serve as biomarkers for monitoring uncontrolled or severe asthma and as prognostic markers for IPF.

Preeclampsia (PE) affects 2–4% of pregnancies, and early detection and intervention can reduce its incidence. Dysregulation of the maternal immune response and red blood cells (RBCs) are key to its development, although early alterations remain unclear. This study analyzed data from 17,955 pregnant women across two centers to explore the relationships among inflammatory markers, RBC indices, and PE via multivariate logistic regression and restricted cubic splines (RCSs). Machine learning integrated inflammatory markers, RBC indices, and maternal risk factors to predict PE risk at 14 weeks, as validated by receiver operating characteristic (ROC) curve analysis. After adjusting for confounders, the lymphocyte (LYMPH) count (OR = 1.27, 95% CI: 1.05–1.53, P = 0.013), monocyte (MONO) count (OR = 2.57, 95% CI: 1.31–5.03, P = 0.006), systemic inflammatory response index (SIRI) (OR = 1.11, 95% CI: 1.01–1.21, P = 0.032), and systemic immune inflammatory index (SII) (OR = 1.01, 95% CI: 1.01–1.01, P = 0.002) were identified as significant risk factors for PE. Nonlinear associations between white blood cell (WBC) count, neutrophil (NEUT) count, platelet (PLT) count, RBC count, and hemoglobin (HGB) and PE were observed via RCS (nonlinear P < 0.05). Further analysis revealed threshold effects for WBC (P = 0.034), with an inflection point at 8.44. Below 8.44, no significant association was found (OR = 0.92, P = 0.307), but above 8.44, each unit increase was linked to a 0.14-fold rise in PE risk (OR = 1.14, P < 0.001). Similar threshold effects were found for the PLT, RBC, and HGB (P < 0.001). A prediction model based on inflammatory markers, RBC indices, and maternal risk factors achieved high performance (ROC = 0.82). LYMPH, MONO, SIRI, and SII were linearly associated with PE, whereas WBC, NEUT, PLT, RBC, and HGB showed nonlinear associations with threshold effects. Early prediction using these indicators is a cost-effective strategy for PE prevention.

Objective: To assess the association between lipid metabolism and fetal fraction, which is a critical factor in ensuring a highly accurate non-invasive prenatal testing (NIPT), and on the rate of screen failures or “no calls” in NIPT.Methods: A total of 4,514 pregnant women at 12–26 weeks of gestation underwent NIPT sequencing and serum lipid measurements. Univariate analysis and multivariate regression models were used to evaluate the associations of serum lipid concentrations with the fetal fraction and the rate of screen failures.Results: The fetal fraction decreased with increased low-density lipoprotein cholesterol and triglyceride (TG) levels, which were significant factors (standardized coefficient: −0.11). Conversely, high-density lipoprotein cholesterol and the interval between the two tests were positively correlated with the fetal fraction. The median fetal fraction was 10.88% (interquartile range, 8.28–13.89%) and this decreased with TG from 11.56% at ≤1.10 mmol/L to 9.51% at >2.30 mmol/L. Meanwhile, multivariate logistic regression analysis revealed that increased TG levels were independently associated with the risk of screen failures. The rate of screen failures showed an increase with TG levels from 1.20% at ≤1.70 mmol/L to 2.41% at >2.30 mmol/L.Conclusions: The fetal fraction and the rate of screen failures in NIPT are affected by TG levels. Meanwhile, in pregnant women with high TG levels, delaying the time between NIPT blood collections can significantly increase the fetal fraction.

Objective: We and others have previously demonstrated that the size-selection enrichment method could remarkably improve fetal fraction (FF) in the early gestational age (GA, 12–13 weeks), suggesting that 9 or 10 weeks should not be used as a threshold for GA in size-selection noninvasive prenatal screening (NIPS). Here, we assessed whether this method was reliable for detecting fetal chromosomal aneuploidy at the earliest GA (6–8 weeks). Methods: Size-selection NIPS for fetal chromosomal aneuploidy was applied to 208 pregnancy plasma samples (102 male and 106 female fetuses), while the 169 pregnancy samples with male fetuses also underwent standard NIPS. Multivariable linear regression models were used to evaluate the association between fold-change of FF and experimental factors. Results: The sensitivity of the cell-free DNA (cfDNA) test in detecting aneuploidy was 100% when screened with FF enrichment, whereas the sensitivity of the same patients was only 62.5% (5/8) without FF enrichment. In the 102 pregnancy samples with male fetuses, FF increased from 6.1% to 15.7%, and the median increase in FF was 2.8-fold with enrichment. Moreover, there was a trend toward an increasing success rate of the cfDNA test from 6 to 13 weeks of gestation, especially when the test success rate reached 100% after 7 weeks with FF enrichment. Multivariate linear regression analysis demonstrated that a lower initial FF, shorter cfDNA size, increased body mass index (BMI), and later GA were all independent predictors of a higher fold-change of FF. Compared with ≤ 120 bp cfDNA fragments, the mean fold-change of FF differences was 0.820 for 121–125 bp, 0.229 for 126–130 bp, − 0.154 for 131–135 bp, − 0.525 for 136–140 bp and − 0.934 for > 140 bp (P_trend < 0.0001), suggesting that fold-change of FF significantly decreased with cfDNA fragments > 125 bp. These results were statistically significant after adjusting for confounding factors in the models for fold-change of FF. Conclusions: The FF enrichment method is a reasonable strategy to detect fetal chromosomal aneuploidy in early pregnancy loss with reduced false negatives and increased test success rate after 7 weeks of GA and should be recommended for patients with early pregnancy loss.