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

OBJECTIVES: To evaluate the feasibility, efficacy and safety of Sentinel cerebral embolic protection device (CEPD) during transcatheter aortic valve replacement (TAVR). This study is a subgroup analysis of the China Moderate to Severe Valvular Heart Disease Registry, which has been registered at the Chinese Clinical Trial Registry (ChiCTR2300075006). METHODS: Patients undergoing TAVR with the Sentinel CEPD from October 2023 to September 2024 were retrospectively enrolled. A total of 80 patients were included, with a median age of 72 (68, 76) years, including 52 males (65.0%) and 28 females (35.0%); 62 patients (77.5%) with tricuspid valves, and 18 patients (22.5%) with bicuspid valves; 34 patients (42.5%) with type Ⅰ aortic arch, 24 patients (30.0%) with type Ⅱ aortic arch, 12 patients (15.0%) with type Ⅲ aortic arch, and 10 patients (12.5%) with bovine-type aortic arch. Clinical data of the patients were summarized and analyzed. The primary endpoints were success rate of Sentinel CEPD implantation, as well as all-cause death, symptomatic stroke, transient ischemic attack, and Sentinel CEPD access vessel complications during hospitalization and within 30 days postoperatively. RESULTS: In the 80 patients, self-expanding valves were used in 68 cases (85.0%) and balloon-expandable valves in 12 cases (15.0%). Seventy-nine patients (98.8%) successfully underwent TAVR with Sentinel CEPD deployment. Macroscopically visible debris was captured in 92.5% (74/80) by filters of Sentinel CEPD. Although the procedure time for Sentinel CEPD placement was slightly longer in patients with bovine-type aortic arch, there was no statistically significant difference in deployment time among different aortic arch types (P>0.05). During hospitalization and within 30 days postoperatively, only one case of transient ischemic attack occurred, and there was no all-cause mortality, symptomatic stroke, or access-site vascular complications related to the Sentinel CEPD observed. CONCLUSIONS The Sentinel CEPD demonstrates high feasibility across aortic arch types, potential efficacy in embolic capture, and excellent safety in TAVR.
Humans ; Transcatheter Aortic Valve Replacement/adverse effects* ; Male ; Female ; Aged ; Embolic Protection Devices ; Retrospective Studies ; Intracranial Embolism/prevention & control* ; Aged, 80 and over ; Aortic Valve Stenosis/surgery* ; Aortic Valve/surgery*

OBJECTIVE: To investigate the factors affecting ferric chloride (FeCl₃) - induced carotid artery thrombosis model experiment. METHODS: After the common carotid artery was damaged by FeCl₃, the injured vessels were dissected for fixation, embedding, frozen section, and then processed HE staining. The carotid thrombus area ratio was calculated. We examined the effect of FeCl₃ concentration (5%, 10% and 15%), reaction time (2, 4 and 6 min), and recipient mouse age (4-5, 6-8 and 10 weeks) on the formation and stability of arterial thrombosis model. The model was injected through the post-glomus venous plexus of mouse eyeball with 0.075 μg/g and 0.1 μg/g R300 to verify the accuracy of the FeCl₃-induced model on thrombus formation by adjusting the platelet number. RESULTS: HE staining showed that thrombus formation induced by 10% and 15% FeCl₃ was more stable, dense and larger than 5% FeCl₃-induced thrombosis. 10% FeCl₃ induced the formation of dense and large thrombosis after 4 and 6 minutes of vascular endothelium injury, while the thrombosis induced for 2 minutes were looser and smaller in area. Mouse age can not affect thrombus formation and stability, because there were no significant differences in the formation of dense thrombus and thrombus area induced by 10% FeCl₃ among three different age groups of mice. CONCLUSION Many factors affect the formation and stability of arterial thrombosis model induced by FeCl₃. This optimal experimental conditions for construction of a stable carotid artery thrombosis model are 10% FeCl₃, 4 minutes for injury, and 6-8 week old mice.
Animals ; Mice ; Ferric Compounds/adverse effects* ; Chlorides ; Disease Models, Animal ; Carotid Artery Thrombosis/chemically induced* ; Male

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

BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

Humans ; Venous Thromboembolism/drug therapy* ; Anticoagulants/administration & dosage* ; Child ; Consensus ; China ; Practice Guidelines as Topic

OBJECTIVE: To analyze the clinical characteristics of venous thromboembolism (VTE) in patients with multiple myeloma (MM) and to identify the risk factors of VTE in MM patients. METHODS: 179 newly diagnosed MM (NDMM) patients admitted to The Second Hospital of Shanxi Medical University from January 2014 to December 2020 who were followed up for more than 6 months were collected, and they were divided into VTE group and control group according to whether combined with VTE. The clinical and laboratory data were compared between the two groups. Mann-whitney U test was used for inter-group comparison of measurement data, Chi-square test or Fisher's exact test was used for inter-group comparison of count data, and multivariate logistic regression analysis was performed to explore the risk factors of VTE in MM patients. RESULTS: Compared with control group, the serum albumin (ALB) level in VTE group was significantly lower (P =0.033), the fibrinogen (FIB) level was significantly higher (P =0.016), and the proportion of patients with D-dimer≥2 000 ng/ml was significantly higher than that in the control group (26.3% vs 4.4%, P =0.002). There was a significant difference in M-component type between the two groups (P =0.028), and the proportion of IgG type in VTE group was higher. There were no statistically significant differences between two groups in age, sex, body mass index (BMI), the proportions of patients with hypertension, diabetes, coronary heart disease and cerebral infarction, white blood cell (WBC) count, platelet (PLT) count, liver and kidney function, plasma cells ratio in bone marrow, serum globulin (GLO), lactate dehydrogenase (LDH), β₂-microglobulin (β₂-MG) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), prothrombin time (PT), activated partial thromboplastin time (APTT), disease stage, thrombosis prevention and the use of immunomodulators (P >0.05). Multivariate logistic regression analysis showed that FIB level (OR=1.578, 95%CI:1.035-2.407, P =0.034), D-dimer≥2 000 ng/ml (OR=5.467, 95%CI:1.265-23.621, P =0.023) and IgG type (OR=4.780, 95%CI: 1.221-18.712, P =0.025) were independent risk factors for VTE in MM patients. CONCLUSION MM patients are prone to VTE, and FIB level, D-dimer≥2 000 ng/ ml and IgG type are independent risk factors for VTE in MM patients.
Humans ; Venous Thromboembolism ; Multiple Myeloma/complications* ; Risk Factors ; Anticoagulants ; Immunoglobulin G ; Retrospective Studies

Objective:To analyze the clinical diagnosis, treatment ，and surgical timing of otogenic intracranial complications. Methods:The clinical data of 11 patients with intracranial complications with ear symptoms as the first manifestation in Department of Otorhinolaryngology Head and Neck Surgery, Qilu Hospital of Shandong University（Qingdao） from December 2014 to June 2022 were collected, including 8 males and 3 females, aged from 4 to 69 years. All patients had complete otoendoscopy, audiology, imaging and etiology examination, and the diagnosis and treatment plan was jointly developed through multidisciplinary consultation according to the critical degree of clinical symptoms and imaging changes. Among the 11 patients, 5 cases were treated with intracranial lesions first in neurosurgery department and middle ear lesions later in otolaryngology, 3 cases of meningitis, were treated with middle ear surgery after intracranial infection control, 1 case was treated with middle ear lesions and intracranial infection simultaneously, and 2 cases were treated with sigmoid sinus and transverse sinus thrombosis conservatively. They were followed up for 1-6 years. Descriptive statistical methods were used for analysis. Results:All the 11 patients had ear varying symptoms, including ear pain, pus discharge and hearing loss, etc, and then fever appeared, headache, disturbance of consciousness, facial paralysis and other intracranial complication. Otoendoscopy showed perforation of the relaxation of the tympanic membrane in 5 cases, major perforation of the tension in 3 cases, neoplasia in the ear canal in 1 case, bulging of the tympanic membrane in 1 case, and turbidity of the tympanic membrane in 1 case. There were 4 cases of conductive hearing loss, 4 cases of mixed hearing loss and 3 cases of total deafness. Imaging examination showed cholesteatoma of the middle ear complicated with temporal lobe brain abscess in 4 cases, cerebellar abscess in 2 cases, cholesteatoma of the middle ear complicated with intracranial infection in 3 cases, and sigmoid sinus thrombophlebitis in 2 cases. In the etiological examination, 2 cases of Streptococcus pneumoniae were cultured in the pus of brain abscess and cerebrospinal fluid, and 1 case was cultured in streptococcus vestibularis, Bacteroides uniformis and Proteus mirabilis respectively. During the follow-up, 1 patient died of cardiovascular disease 3 years after discharge, and the remaining 10 patients survived. There was no recurrence of intracranial and middle ear lesions. Sigmoid sinus and transverse sinus thrombosis were significantly improved. Conclusion:Brain abscess, intracranial infection and thrombophlebitis are the most common otogenic intracranial complications, and cholesteatoma of middle ear is the most common primary disease. Timely diagnosis, multidisciplinary collaboration, accurate grasp of the timing in the treatment of primary focal and complications have improved the cure rate of the disease.
Female ; Humans ; Male ; Brain Abscess/therapy* ; Cholesteatoma ; Deafness/etiology* ; Hearing Loss/etiology* ; Lateral Sinus Thrombosis/therapy* ; Retrospective Studies ; Thrombophlebitis/therapy* ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Cholesteatoma, Middle Ear/therapy* ; Central Nervous System Infections/therapy* ; Sinus Thrombosis, Intracranial/therapy* ; Ear Diseases/therapy*

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

Humans ; China ; Consensus ; Purpura, Thrombocytopenic, Idiopathic/therapy* ; Thrombocytopenia/therapy* ; Thromboembolism/therapy*