Yancheng Central Blood Station

This study aimed to develop novel, highly specific monoclonal antibodies for the rapid and precise detection of the plasmin-α2-antiplasmin complex (PIC), an early biomarker indicative of fibrinolytic activation. This approach addresses the limitations of existing methods, which are often time-consuming and susceptible to interference from abundant free plasminogen and α2-antiplasmin in plasma, thereby improving the diagnosis and management of venous thromboembolism (VTE) and related disorders. We successfully generated self-assembled PIC complexes via co-expression technology to immunize mice and subsequently screened a pair of monoclonal antibodies (4C11 and 3 × 105) that specifically target novel epitopes of the PIC, exhibiting high affinity and specificity, with affinity constants of 1.0 × 10-12 M and 8.9 × 10-10 M, respectively. Utilizing this antibody pair, we established a single-integrated chemiluminescence immunoassay capable of completing detection within 15 minutes. The developed assay demonstrated excellent analytical performance, characterized by a detection limit as low as 0.06 µg mL-1, a broad linear range (0.08-40 µg mL-1), and a total coefficient of variation below 10%. Multicenter clinical evaluations further confirmed strong concordance with the reference method (R2 = 0.99), alongside enhanced sensitivity and specificity, as evidenced by an area under the curve (AUC) of 0.95 compared to 0.90. In summary, we have developed a rapid, high-performance PIC detection platform based on novel monoclonal antibodies. This platform is compatible with point-of-care testing (POCT) and represents a highly promising and reliable tool for the clinical assessment of hyperfibrinolysis.

This study reports the development of a novel signal amplification carrier based on the soluble macromolecular polysaccharide Ficoll400 to enhance the sensitivity of chemiluminescent immunoassays (CLIA), with a particular focus on detecting low-abundance biomarkers, such as high-sensitivity cardiac troponin I (hs-cTnI). The carrier was constructed via the reductive amination of Ficoll400, followed by conjugation with streptavidin (SA), thereby generating dense SA binding sites capable of attaching numerous biotinylated horseradish peroxidase (Bio-HRP) molecules to amplify the chemiluminescent signal. Comparative analyses with other polysaccharides (Dextran T500 and hyaluronic acid) demonstrated that Ficoll400 conjugates, especially when aminated with l-lysine, provided superior signal enhancement with minimal background noise, improving the signal-to-noise ratio by up to 140-fold. Characterization by SDS-PAGE, dynamic light scattering, and transmission electron microscopy confirmed the formation of large macromolecular structures conducive to signal amplification. Optimization of experimental parameters, such as conjugation ratios, pH, buffer composition, and surfactant presence, further enhanced the assay performance. The developed hs-cTnI CLIA method exhibited excellent analytical sensitivity, with a limit of detection of 0.5 pg·mL-1 and a limit of quantitation of 0.9 pg·mL-1, alongside robust stability under accelerated and onboard conditions and high precision, with coefficients of variation below 10%. Clinical sample testing demonstrated strong correlation and consistency with a commercial hs-cTnI assay, confirming the method's reliability and potential for clinical application. Overall, the Ficoll400-SA amplification carrier provides a stable, biocompatible, and easily prepared platform that significantly enhances immunoassay sensitivity, with promising applications for the detection of various low-abundance biomarkers in vitro.

Tumorigenesis is closely related to an imbalance in cell death regulation. PANoptosis is a recently characterized form of programmed cell death that integrates the molecular features of cellular pyroptosis, apoptosis and necrotic apoptosis through the assembly of a multiprotein complex termed the PANoptosome. Beyond its role in cancer initiation and progression, PANoptosis is intricately linked to immune responses within the tumor microenvironment, thus offering new avenues for therapeutic intervention. The present review outlines the interplay among different cell death pathways, highlights the defining characteristics and assembly mechanisms of PANoptosis, as well as discusses its functional roles in cancer biology. Additionally, the implications of PANoptosis in tumor immunity and the potential of targeting this pathway in cancer therapy are explored.

Background: Previous studies have established an association between heart rate variability (HRV) and physiological processes such as inflammation and immune responses. This investigation aims to determine if there is a correlation between HRV and the levels of IgG antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 in individuals. Methods: This study involved 247 individuals who had recovered from COVID-19 and participated in a blood donation drive at the Central Blood Station in Liangshan, Sichuan, from March 1 to March 10, 2023. During these sessions, five-minute electrocardiograms were recorded while the donors were at rest, to analyze HRV in both time and frequency domains. The levels of IgG antibodies against the SARS-CoV-2 RBD protein were measured using the enzyme-linked immunosorbent assay (ELISA). Results: Bivariate correlation analysis illustrated that the spectral components of HRV — specifically the very low frequency power, low frequency power, and the low/high frequency ratio — are significantly inversely correlated with the levels of IgG antibodies targeting the SARS-CoV-2 RBD protein (P-values of 0.048, 0.031, and 0.076, respectively). After adjusting for confounding factors such as age and gender in a multivariate linear regression model, the very low and low frequency powers persisted as independent predictors of the IgG antibody levels against SARS-CoV-2 RBD protein (P-values of 0.024 and 0.047, respectively). Conclusions: The frequency domain indicators of HRV are independent determinants influencing the levels of IgG antibodies to the SARS-CoV-2 RBD protein. Further research is required to elucidate the underlying physiological and pathological mechanisms.

While elevated fibrinogen-to-albumin ratio (FAR) correlates with all-cause mortality in adults, its prognostic value in pediatric intensive care units (PICUs) remains unclear. This study aimed to investigate the association between FAR and in-hospital all-cause mortality in critically ill pediatric patients. We conducted a retrospective cohort study analyzing the PIC database from 2010 to 2018. Blood samples for fibrinogen and serum albumin were collected within 24h of admission. The primary outcome was 28-day all-cause mortality. We utilized multivariable Cox proportional hazards regression, smooth curve fitting, and Kaplan-Meier survival curves, along with subgroup analyses and a two-piecewise linear regression model to assess associations. A total of 5,087 patients (mean age 1.4 years; 44.7% female) were included. The 28-day mortality rate was 4.7% (240/5,087). FAR was independently associated with mortality risk (HR: 0.83, 95% CI: 0.70-0.98; P = 0.031). Higher FAR tertiles correlated with decreased mortality risk (HR: 0.66, 95% CI: 0.44-1.00; P = 0.005). The FAR-mortality relationship was L-shaped, with a threshold around 0.648. The effect sizes on the left and right sides of the inflection point were 0.076 (95% CI: 0.025-0.234, P < 0.001) and 1.126 (95% CI: 0.669-1.895, P = 0.656), respectively. No significant interactions were observed between FAR and 28-day mortality, except in patients with malignant cancer (P for interaction > 0.05). The results of the sensitivity analysis remained stable. This study reveals an L-shaped relationship between FAR and 28-day in-hospital all-cause mortality in PICU patients, suggesting that FAR may serve as a prognostic marker for mortality in critically ill children.

Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exs) have been found to exhibit therapeutic effects on inflammatory bowel disease (IBD). However, due to the harsh environment of the gastrointestinal tract, exosomes, as a type of biological drug or carrier of bio-active substances, are still delivered by tail vein injection. In this study, hucMSC-Ex were coated with poly (lactic-co-glycolic acid) (PLGA) polymer to form microparticles, PLGA-hucMSC-Ex, by double emulsion method. The oral administration of PLGA-hucMSC-Ex particles alleviated inflammation in the mice model of IBD by reversing IBD-induced epithelial-mesenchymal transition (EMT). This provides an alternative to exploring IBD treatments, with potential clinical application to relieve IBD in patients.

To compare and analyze the changes of aggregation rate and routine parameters of platelets stored in temperature cycle, cold storage at 4 ℃ and oscillating storage at 22 ℃, so as to provide more experimental data for platelet preservation methods. Blood samples were collected at 5 time points on the 1st, 2nd, 3rd, 4th and 6th day after platelet cycling preservation at temperature, cold storage at 4 ℃, and oscillating storage at 22 ℃. Platelet maximum aggregation rate (MAR) and routine parameters including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and platelet-larger cell ratio (P-LCR) were detected. The platelet MAR of three groups showed a significant decrease trend with the preservation time, the fastest decrease was in the 22 ℃ group, the slowest was in the 4 ℃ group, and the temperature cycle group was between the two groups. On the 3rd day of preservation, the platelet MAR in 4 ℃ group was still in the normal range (MAR>60%), while in temperature cycle group was about 50%, and in 22 ℃ group was the lowest. On the 4th day of preservation, platelet MAR in all the three groups was lower than 50%, and that in temperature cycle group was significantly lower than in 4 ℃ group but higher than in 22 ℃ group (both P < 0.05). On the 6th day of preservation, platelet MAR in the temperature cycle group was significantly lower than that in the 4 ℃ group ( P <0.05), but there was no statistically significant difference compared to 22 ℃ group (P >0.05). PLT values in the three groups were all significantly decreased with the preservation time extension, and were significantly lower than those in the early stage of preservation within 6 days (all P < 0.05). PDW in temperature cycle group had no significant change within 6 days of preservation, but MPV and P-LCR were significantly increased. MPV, PDW and P-LCR all decreased significantly in 4 ℃ group within 6 days of preservation but increased in 22 ℃ group. Under the same storage days, PLT value of temperature cycle group had no significant difference with that of 4 ℃ group and 22 ℃ group, while MPV, PDW and P-LCR values were significantly higher than 4 ℃ group but lower than 22 ℃ group (all P < 0.05). The aggregation function and routine parameters changes of temperature circulating preserved platelets are between 4 and 22 ℃.

Thyroid cancer (TC) is the prevailing malignancy that impacts the endocrine system, accounting for 1% of all recently diagnosed malignancies in humans. The incidence of TC has been continuously increasing, which can be attributed to advancements in clinical diagnostic technology. However, the mechanisms behind the development of TC are still not well understood. TC is classified into four pathological forms: medullary thyroid cancer, papillary thyroid cancer (PTC), follicular thyroid cancer, and poorly differentiated TC. PTC constitutes more than 80% of all TC cases globally. Current research indicates that complex genetic and cellular processes could be responsible for the growth and spread of TC. Next-generation sequencing (RNA-seq) of 79 PTC samples and their corresponding normal thyroid tissues was performed to investigate the molecular mechanisms of PTC. An analysis of RNA-seq data from a local cohort from The Cancer Genome Atlas (TCGA) revealed that, compared with normal tissues, PTC tissues presented elevated FAM20C expression levels. In vitro, the function of FAM20C was validated with small interfering RNA (siRNA). Gene set enrichment analysis (GSEA) revealed the pathways influenced by FAM20C. A western blot experiment was used to investigate protein expression levels associated with epithelial‒mesenchymal transition (EMT). In conclusion, by regulating EMT, FAM20C facilitates PTC cell proliferation and metastasis.