2.Unveiling the molecular features and diagnosis and treatment prospects of immunothrombosis via integrated bioinformatics analysis.
Yafen WANG ; Xiaoshuang WU ; Zhixin LIU ; Xinlei LI ; Yaozhen CHEN ; Ning AN ; Xingbin HU
Chinese Journal of Cellular and Molecular Immunology 2025;41(3):228-235
Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans
;
Computational Biology/methods*
;
Lupus Erythematosus, Systemic/immunology*
;
Protein Interaction Maps/genetics*
;
Venous Thromboembolism/therapy*
;
Matrix Metalloproteinase 9/genetics*
;
Extracellular Traps/metabolism*
;
Gene Regulatory Networks
;
Thrombosis/immunology*
;
Graft vs Host Disease/genetics*
;
Gene Expression Profiling
3.Optimization of flow rate and orientation of outflow graft at implantation for patients with left ventricular assist device.
Yongyi WANG ; Li SHI ; Shijun HU ; Xiao TAN ; Tianli ZHAO
Journal of Central South University(Medical Sciences) 2025;50(3):457-468
OBJECTIVES:
A ventricular assist device (VAD) is an electromechanical device used to assist cardiac blood circulation, which can be employed for the treatment of end-stage heart failure and is most commonly placed in the left ventricle. Despite enhancing perfusion performance, the implantation of left ventricular assist device (LVAD) transforms the local intraventricular flow and thus may increase the risk of thrombogenesis. This study aims to investigate fluid-particle interactions and thromboembolic risk under different LVAD configurations using three-dimensional (3D) reconstruction models, focusing on the effects of outflow tract orientation and blood flow rates.
METHODS:
A patient-specific end-diastolic 3D reconstruction model was initially constructed in stereo lithography (STL) format using Mimics software based on CT images. Transient numerical simulations were performed to analyze fluid-particle interactions and thromboembolic risks for LVAD with varying outflow tract orientations under 2 flow rates (4 L/min and 5 L/min), using particles of uniform size (2 mm), and a blood flow rate optimization protocol was implemented for this patient.
RESULTS:
When the LVAD flow rate was 5 L/min, helicity and flow stagnation of the blood flow increased the particle residence time (RT) and the risk of thrombogenesis of the aortic root. The percentage of particles traveling toward the brachiocephalic trunk was up to 20.33%. When the LVAD flow rate was 4 L/min, blood turbulence in the aorta was reduced, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 10.54%. When the LVAD blood flow rate was 5 L/min and the direction of the outflow pipe was optimal, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 11.22%. A 18-month follow-up observation of the patient revealed that the LVAD was in good working order and the patient had no complications related to the implantation of LVAD.
CONCLUSIONS
Implantation of LVAD results in a higher risk of cerebral infarction; When implanting LVAD with the same outflow tract direction, optimizing flow velocity and outflow tract can reduce the risk of cerebral infarction occurrence.
Heart-Assist Devices/adverse effects*
;
Humans
;
Heart Failure/physiopathology*
;
Blood Flow Velocity
;
Thromboembolism/prevention & control*
;
Models, Cardiovascular
;
Heart Ventricles/physiopathology*
;
Imaging, Three-Dimensional
4.Comparative performance of bleeding risk scores in critically ill and non-critically ill patients receiving prophylactic enoxaparin admitted at a tertiary hospital: A prospective cohort study.
Rowena Q. JAVONILLO ; Paolo Joel T. NOCOM ; Jasmin Melissa B. BERNARDO
Philippine Journal of Cardiology 2025;53(2):35-41
BACKGROUND
Balancing the benefits of preventing venous thromboembolism (VTE) against the risks of bleeding is important for patients who need prophylactic anticoagulants. This study compared which of the bleeding scores (IMPROVE and HAS-BLED BRS scores) is better at predicting anticoagulant-related bleeding events in critically ill and non-critically ill patients at a tertiary hospital who received prophylactic enoxaparin.
METHODOLOGYSixty-nine (69) patients in the ICU and ward who received prophylactic enoxaparin were included in the study and followed until discharge. Demographic data, comorbidities and IMPROVE and HAS-BLED BRS scores were recorded, and bleeding events monitored.
RESULTSDuring the study, 16% (11/69) of the study population experienced bleeding events, both major and minor. Patients with IMPROVE BRS ≥7 (high risk) were more likely to bleed than those with scores ofCONCLUSION
In patients receiving prophylactic anticoagulants for VTE, the IMPROVE BRS was better at predicting major anticoagulant-related bleeding events than the HAS-BLED BRS, with higher sensitivity, specificity and accuracy. Both risk scoring systems are useful for assessing bleeding risk before starting pharmacologic VTE prophylaxis, but the IMPROVE BRS is more accurate.
Human ; Venous Thromboembolism
7.Recent advances in the application of TAT, TM, t-PAIC and PIC in thromboembolism.
Yong Jian LI ; Qi ZHANG ; Hong Chun WANG
Chinese Journal of Preventive Medicine 2023;57(10):1693-1703
Thromboembolism is a crucial part of the global disease burden. It has high incidence, high mortality and disability rates, and the mechanism of occurrence and development is extremely complex. It is difficult to detect the disease in the early stage so that we have trouble with clinical prevention and treatment in general. At present, four items of blood coagulation and D-dimer have been widely used in the evaluation and auxiliary diagnosis of thromboembolism, the monitoring of effect for antithrombotic drugs and other fields. The thrombus biomarkers including thrombin-antithrombin complex (TAT), thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC) and α2-plasmin inhibitor-plasmin complex (PIC) fill the gap of laboratory diagnosis before clinical symptoms appear in some degree. This article aims to explain the current application status of TAT, TM, t-PAIC and PIC in thromboembolism and explore their potential application value, so as to provide a reference for selecting appropriate early monitoring indicators for high-risk population of thromboembolism.
Humans
;
Tissue Plasminogen Activator
;
Plasminogen Inactivators
;
Thrombomodulin
;
Thromboembolism
;
Biomarkers
8.Recent advances in the application of TAT, TM, t-PAIC and PIC in thromboembolism.
Yong Jian LI ; Qi ZHANG ; Hong Chun WANG
Chinese Journal of Preventive Medicine 2023;57(10):1693-1703
Thromboembolism is a crucial part of the global disease burden. It has high incidence, high mortality and disability rates, and the mechanism of occurrence and development is extremely complex. It is difficult to detect the disease in the early stage so that we have trouble with clinical prevention and treatment in general. At present, four items of blood coagulation and D-dimer have been widely used in the evaluation and auxiliary diagnosis of thromboembolism, the monitoring of effect for antithrombotic drugs and other fields. The thrombus biomarkers including thrombin-antithrombin complex (TAT), thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC) and α2-plasmin inhibitor-plasmin complex (PIC) fill the gap of laboratory diagnosis before clinical symptoms appear in some degree. This article aims to explain the current application status of TAT, TM, t-PAIC and PIC in thromboembolism and explore their potential application value, so as to provide a reference for selecting appropriate early monitoring indicators for high-risk population of thromboembolism.
Humans
;
Tissue Plasminogen Activator
;
Plasminogen Inactivators
;
Thrombomodulin
;
Thromboembolism
;
Biomarkers
9.The clinical value of serum GPC3 level in predicting recurrence of patients with primary hepatocellular carcinoma.
Pei Ru ZHANG ; Xiao Lu MA ; Lin GUO ; Ren Quan LU
Chinese Journal of Preventive Medicine 2023;57(6):885-890
Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ2=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ2=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ2 =4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ2=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.
Humans
;
Carcinoma, Hepatocellular/pathology*
;
Liver Neoplasms/diagnosis*
;
alpha-Fetoproteins/analysis*
;
Biomarkers, Tumor
;
Glypicans
;
Ascites
;
Venous Thromboembolism
;
Peritoneal Neoplasms
;
Liver Cirrhosis


Result Analysis
Print
Save
E-mail