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Sepsis, a lethal organ dysfunction syndrome driven by aberrant host responses to infection, intertwines excessive inflammatory responses and dysregulated coagulation processes in its pathophysiology. Emerging research reveals the complement terminal membrane attack complex C5b-9 orchestrates ultralarge von Willebrand factor (ULVWF) release from vascular endothelial cells (ECs) through multifaceted mechanisms: C5b-9 compromises EC membrane integrity, activates calcium influx cascades, and provokes NLRP3 inflammasome signaling, triggering massive exocytosis of ULVWF stored within Weibel-Palade bodies (WPBs). When ADAMTS13 activity falters, undegraded ULVWF complexes with platelets to spawn microthrombi, precipitating microvascular occlusion and multiorgan collapse. Strikingly, elevated plasma von Willebrand factor (vWF) antigen levels in sepsis patients correlate robustly with endothelial injury, thrombocytopenia, and mortality-underscoring C5b-9-driven vWF release as a linchpin of septic coagulopathy. Current therapeutic strategies targeting these pathways, including recombinant ADAMTS13 (rhADAMTS13), N-acetylcysteine (NAC), and complement inhibitors like eculizumab, face limitations in clinical translation, necessitating further validation of their efficacy. Additionally, investigating complement regulatory molecules such as CD59 may unlock novel therapeutic avenues. Deciphering the intricate interplay within the C5b-9-vWF axis and advancing precision therapies hold transformative potential for ameliorating sepsis outcomes.

Subarachnoid hemorrhage (SAH) is a disease with high mortality and morbidity, and its pathophysiology is complex but poorly understood. To investigate the potential therapeutic targets post-SAH, the SAH-related feature genes were screened by the combined analysis of transcriptomics and metabolomics of rat cortical tissues following SAH and proteomics of cerebrospinal fluid from SAH patients, as well as WGCNA and machine learning. The competitive endogenous RNAs (ceRNAs) and transcription factors (TFs) regulatory networks of the feature genes were constructed and further validated by molecular biology experiments. A total of 1336 differentially expressed proteins were identified, including 729 proteins downregulated and 607 proteins upregulated. The immune microenvironment changed after SAH and the changement persisted at SAH 7d. Through multi-omics and bioinformatics techniques, five SAH-related feature genes (A2M, GFAP, GLIPR2, GPNMB, and LCN2) were identified, closely related to the immune microenvironment. In addition, ceRNAs and TFs regulatory networks of the feature genes were constructed. The increased expression levels of A2M and GLIPR2 following SAH were verified, and co-localization of A2M with intravascular microthrombus was demonstrated. Multiomics and bioinformatics tools were used to predict the SAH associated feature genes confirmed further through the ceRNAs and TFs regulatory network development. These molecules might play a key role in SAH and may serve as potential biological markers and provide clues for exploring therapeutic options.

Patient-specific cerebral aneurysms exhibit complex hemodynamics insights that influence thrombus formation, wall remodeling, and therapeutic delivery. The article presents a high-fidelity, multi-parametric CFD analysis of nine distinct aneurysm cases using 3-D model-resolved meshes, non-Newtonian Casson rheology, and steady-state flow conditions. Further, the Lagrangian particle tracking was employed to assess drug transport and hemodynamic metrics such as WSS and normalized residence time (NRT) were evaluated, along with vortex dynamics, indicators including helicity ( H ) and Q criterion to characterize rotational flow structures. Results reveal that narrowed neck models (m 1 , m 2 , m 5 , m 8 ) exhibit weak vortex structures and dominant axial washout (velocity magnitude < 0.10 m/s; NRT < 0.2), while sac-expanded geometries (m 3 , m 4 , m 6 , m 9 ) support robust helical vortices ( H  > 40 m²/s², Q  > 0) and elevated residence times. Regions of low WSS (τ w  < 0.5 Pa) spatially co-localize with high NRT and potential thrombogenicity, whereas high WSS (τ w  > 2.5 Pa) associates with jet impingement zones and possible endothelial damage. Notably, sharp WSS gradients are identified as destabilizing hemodynamic factors. Rheological analysis reveals a critical threshold at γ̇ ≈ 415 s⁻¹ ( µ  ≈ 6.4 mPa·s), distinguishing thrombosis-prone regions (low γ̇, high µ) from stable zones (high γ̇, low µ). Particle transport studies show that effective drug retention occurs in high-helicity, wide neck models for Stokes number (St = 0.1–1), while laminar-dominant aneurysmal flows demonstrate poor drug deposition due to axial convection. Overall, the findings underscore that aneurysm stability and therapeutic outcomes are governed by the interplay of aneurysm induced flow structures, WSS heterogeneity, non-Newtonian rheology, and vortex coherence are refining rupture risk assessments and optimizing endovascular drug delivery strategies.

Objective To explore the relationship between leukocyte count and renal function in patients with lupus nephritis (LN). Methods We performed a retrospective cross-sectional study of 100 patients with LN admitted to the Department of Nephrology between 1 January 2015 and 30 December 2023. Based on tertile of leukocyte count, they were allocated to Low, Medium, or High groups. The demographic, clinical, and pathologic characteristics of the groups were compared and the relationship between leukocyte count and renal function was analyzed using multiple linear regression analysis. Results After adjustment for age, albumin, 24-hour proteinuria, serum complement factor 3, hemoglobin, blood pressure, systemic lupus erythematosus disease activity index score, and histologic parameters, a linear relationship was identified between leukocyte count and renal function (regression coefficient −2.852; 95% confidence interval: −5.161, −0.543). Therefore, for every 1 × 109/L increase in leukocyte count, the estimated glomerular filtration rate would decrease by 2.85 mL/minute. Conclusion There is an independent linear relationship between leukocyte count and renal function. Leukocyte recruitment into the kidney is a critical step in the progression of LN, and as the leukocyte count increases, renal function gradually declines. Leukocyte count may represent a sensitive biomarker of the progression and prognosis of LN.

Abstract Background Several side effects have been reported after mRNA COVID-19 vaccinations. Nonetheless, the risk of pulmonary hypertension (PH) is rarely reported. Most cases with acute PH following vaccination were due to macropulmonary embolism secondary to deep vein thrombosis. However, acute PH due to microthrombus formation after COVID-19 vaccination has not been reported before, although a microthrombus has been considered to lead to the dysfunction of multiple organs, particularly in patients infected with COVID-19. Case summary A 63-year-old woman without any past medical history presented to our hospital with facial and bilateral pedal oedema and progressive dyspnoea on exertion. Her symptoms began the day after her second COVID-19 vaccination and developed gradually, which prompted her to seek consultation in our hospital 6 weeks later. An echocardiogram revealed substantially elevated right heart pressure, and cardiac catheterization revealed high pulmonary artery pressure (mean PAP, 30 mmHg). Contrast-enhanced computed tomography and venous echography revealed no apparent thrombus, and ventilation/perfusion (V/Q) scintigraphy revealed no V/Q mismatch. However, elevated D-dimer indicated the presence of a coagulation–fibrinolysis system in her body; thus, heparin therapy was initiated intravenously on Day 3 for 4 days, followed by direct oral anticoagulants ended on Day 16. Her symptoms substantially improved as her D-dimer level decreased, and a follow-up cardiac catheterization on Day 14 revealed a decline in mean PAP (15 mmHg). Discussion Our case suggests that the presence of acute PH is likely due to microangiopathy. Further studies are required to reveal the relationship between immune responses and microthrombus formation after COVID-19 vaccination.

Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is a useful proven imaging modality in the management of many types of cancers. It is being used at various stages of treatment of cancer. Knowledge regarding the physiological biodistribution and false-positive findings should be kept in mind for correct interpretation. Pulmonary FDG uptake can be due to different causes such as infection, inflammation, and metastases which are invariably associated with structural abnormality on CT. In rare circumstances, there can be a focus of FDG uptake in the lung with no corresponding structural abnormality which might be due to an inflammatory vascular microthrombus or due to iatrogenic microembolism caused during the injection of radiotracer. It is important to be aware of this as it can cause difficulty in interpreting the scan and can lead to false-positive findings. It also highlights the importance of hybrid imaging in the form of PET-CT as there is a definite possibility of misinterpreting this as a site of metastasis in a known carcinoma patient if there was no corresponding CT image.

To investigate whether Huisheng Oral Solution has an anticoagulant effect in a rat model of thrombosis. A total of 40 male SD rats were equally and randomly divided into four groups: blank group, model group, and two treatment groups (A and B). Rats were subcutaneously injected with carrageenan to induce thrombosis. Rats in the treatment group A were intragastrically administered with Huisheng Oral Solution at a dose of 2 ml/100 g body weight (once per 8 hours), 72 hours after carrageenan injection, while those in the treatment group B were administered with Huisheng Oral Solution both 72 hours before and after induction of thrombosis. Blood samples were collected 24, 48, and 72 hours after carrageenan injection for measurements of prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (FIB), prothrombin activity (PTA), platelets (PLT), fibrin degradation products (FDPs), and D-dimer. Lung, liver, and mesentery samples were taken 72 hours after carrageenan injection for histopathological analysis. The numbers of microthrombi in sections of different tissue samples were counted under a microscope. Blood parameters among each group were compared using the Welch test, the Kruskal-Wallis test, or the SNK test after testing for normality, while the number of microthrombi was compared using the Bonferroni test. Compared to those in the model group, PT, APTT, and INR were significantly prolonged or increased while FIB was significantly reduced at the majority of time points in the two treatment groups (P < 0.05 for all). The levels of FDPs and D-dimer and PLT counts at the majority of time points were significantly lower (P < 0.05 for all), and the numbers of microthrombi in lung, liver, and mesentery samples were significantly decreased (P < 0.05 for all) in the two treatment groups. The above parameters at the majority of time points showed no significant differences between the two treatment groups. Huisheng Oral Solution can significantly improve coagulation parameters, fibrinolysis parameters, and PLT count, and reduce blood hypercoagulability and microthrombosis, suggesting that Huisheng Oral Solution has an anticoagulant effect in a rat model of thrombosis.

With endocrinopathic laminitis, there is no evidence suggesting that platelet activation or microthrombus formation occurs in insulin dysregulation related to either equine metabolic syndrome (EMS) or pituitary pars intermedia dysfunction (PPID). This chapter reviews the normal physiologic processes involved in thrombosis and coagulation (with emphasis on platelets). It discusses the possible involvement of these mechanisms in the pathophysiology of laminitis. Although attention is focused primarily on SRL, endocrinopathic and supporting limb laminitis is also discussed. The role of thrombosis and platelet activation in the pathogenesis of this condition is not clear, but some possible mechanisms will be discussed below. Systemic inflammation and/or sepsis in carbohydrate overload (CHO) models would appear to be the cause of the observed platelet activation, coagulation abnormalities, and microthrombus formation.

Effects of okadaic acid (OA) on mucosal damage were examined in rat colon. OA was sprinkled on rat colon mucosa under observation with an electronic-endoscopic system, and OA was also applied to the in vivo microscopic field. The OA-induced changes in transepithelial conductance (Gt) were measured by the Ussing voltage clamp technique. By endoscopic observation, the luminal sprinkling of OA (60 nmol/kg) evoked transient microthrombi in the submucosal venule, which was followed by mucosal edema. Histological study after endoscopic observation showed submucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi were also detected by in vivo microscopy. By electrophysiological study after endoscopic observation with and without OA addition, the basal Gt values were 54+/-6.2 and 36.2+/-4.2 mS/cm2, respectively (P < 0.01). Furthermore in control rats, the serosal addition of OA evoked an increase in Gt in a concentration-dependent manner without increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibited OA-induced Gt change by 60%. These results indicate that OA evokes an increase in paracellular permeability of epithelium. We conclude that the developed microthrombi are the first key event of OA-induced mucosal damage, followed by an increase in permeability in the submucosal venule and in the paracellular pathway of the epithelium.