Xi-He Zhang

Background: Venous thromboembolism (VTE) is a globally prevalent severe disease associated with high morbidity and mortality. Currently, thrombomodulin (TM), fibrinogen degradation product (FDP), thromboelastography have been the subject of several research pertaining to VTE; However, the combined diagnostic efficacy of these tests for VTE remains unclear. Therefore, we proposed to investigate the diagnostic efficacy of TM, FDP, thrombelastography in predicting VTE. Methods: The patients with traumatic fracture included in the study were divided into a VTE group (n = 44) and a control group (n = 56) based on imaging diagnosis. Spearman correlation was employed to analyze the relationship between coagulation-related markers and thromboelastography indices. Variables were analyzed using multifactorial logistic stepwise regression. Statistically significant indicators were included in the receiver operating characteristic curve to evaluate their diagnostic efficacy for VTE. Results: The VTE group showed significantly higher levels of multiple coagulation-related parameters and thromboelastography indices compared to the control group. Specifically, D-dimer levels were 8.87 (4.77, 15.07) mg/L in the VTE group versus 2.36 (1.07, 5.73) mg/L in the control group ( P < 0.001), and FDP levels were 36.45 (11.34, 73.75) μg/mL versus 7.96 (4.57, 12.73) μg/mL ( P < 0.001). TM levels were also elevated in the VTE group at 11.74 (9.26, 13.27) TU/mL compared to 8.60 (7.20, 11.60) TU/mL in controls ( P = 0.001). Among thromboelastography parameters, maximum amplitude (MA) was 72.06 ± 7.61 mm in the VTE group versus 67.03 ± 7.21 mm in controls ( P = 0.001), and clot intensity (G) was 13,259.75 (9,346.48, 18,545.83) d/sc versus 9,659.70 (8,009.33, 13,480.40) d/sc ( P = 0.004). Conversely, the blood clot formation rate was lower in the VTE group (1.25 [0.83, 1.40] vs. 1.30 [1.10, 1.58], P = 0.037). Linear correlation analysis revealed significant positive associations between platelet counts and both MA (r = 0.612, P < 0.001) and G (r = 0.588, P < 0.001). Multivariate logistic stepwise regression identified FDP (OR = 1.047, 95% CI: 1.025–1.070, P < 0.001), TM (OR = 1.215, 95% CI: 1.033–1.429, P = 0.019), and MA (OR = 1.104, 95% CI: 1.026–1.188, P = 0.008) as independent risk factors for VTE. ROC curve analysis demonstrated that the combined model of these three markers achieved the highest diagnostic efficacy, with an area under the curve (AUC) of 0.860 (95% CI: 0.789–0.931), sensitivity of 70.5%, and specificity of 85.7%. Conclusion: Combined testing of FDP, TM, and MA holds clinical significance for clinicians to early predict the risk of VTE in post-traumatic fracture patients and implement preventive measures.

Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis.

The mortality rate of young female COVID-19 patients is reported to be lower than that of young males but no significant difference in mortality was found between female and male COVID-19 patients aged over 65 years, and the underlying mechanism is unknown. We retrospectively analyzed clinical characteristics and outcomes of severely ill pre- and post-menopausal COVID-19 patients and compared with age-matched males. Of the 459 patients included, 141 aged ≤55, among whom 19 died (16 males vs. 3 females, p55 years (n=318), 115 died (47 females vs. 68 males, p=0.149). In patients ≤55 years old, the levels of NLR, median LDH, median c-reactive protein and procalcitonin were significantly higher while the median lymphocyte count and LCR were lower in male than in female (all p<0.0001). In patients over 55, these biochemical parameters were far away from related normal/reference values in the vast majority of these patients in both genders which were in contrast to that seen in the young group. It is concluded that the mortality of severely ill pre-menopausal but not post-menopausal COVID-19 female patients is lower than age-matched male. Our findings support the notion that estrogen plays a beneficial role in combating COVID-19.

Hepatocellular carcinoma (HCC), one of the most common and lethal tumors worldwide, is usually not diagnosed until the disease is advanced, which results in ineffective intervention and unfavorable prognosis. Small molecule targeted drugs of HCC, such as sorafenib, provided only about 2.8 months of survival benefit, partially due to cancer stem cell resistance. There is an urgent need for the development of new treatment strategies for HCC. Tumor immunotherapies, including immune check point inhibitors, chimeric antigen receptor T cells (CAR-T) and bispecific antibodies (BsAb), have shown significant potential. It is known that the expression level of glypican-3 (GPC3) was significantly increased in HCC compared with normal liver tissues. A bispecific antibody (GPC3-S-Fabs) was reported to recruit NK cells to target GPC3 positive cancer cells. Besides, bispecific T-cell Engagers (BiTE), including GPC3/CD3, an aptamer TLS11a/CD3 and EpCAM/CD3, were recently reported to efficiently eliminate HCC cells. It is known that immune checkpoint proteins programmed death-1 (PD-1) binding by programmed cell death-ligand 1 (PD-L1) activates immune checkpoints of T cells. Anti-PD-1 antibody was reported to suppress HCC progression. Furthermore, GPC3-based HCC immunotherapy has been shown to be a curative approach to prolong the survival time of patients with HCC in clinically trials. Besides, the vascular endothelial growth factor (VEGF) inhibitor may inhibit the migration, invasion and angiogenesis of HCC. Here we review the cutting-edge progresses on mechanisms and clinical trials of HCC immunotherapy, which may have significant implication in our understanding of HCC and its immunotherapy.

Aikeqing (AKQ) has been shown in clinical studies to improve quality of life of HIV/AIDS patients, but anti-HIV activity has not been determined. The SHIV-infected macaque is an important animal model for testing antiviral drugs. This study aimed to determine the anti-HIV activity of AKQ in chronically SHIV89.6-infected Chinese rhesus macaques. Nine Chinese rhesus macaques were inoculated intravenously with SHIV89.6 virus. At 11 weeks post-infection, the animals were arbitrarily divided into three groups: high-dose (AKQ 1.65 g/kg; n = 3), low-dose (AKQ 0.55 g/kg; n = 3), and control (water 1 mL/kg; n = 3). Treatment was administered by the intragastric gavage route once-daily for 8 weeks. Blood (5 mL) was collected biweekly. Viral loads were analyzed by real-time quantitative RT-PCR assays, and T cell counts were monitored by FACS analyses throughout the treatment. AKQ induced a persistent decline (P = 0.02) in plasma viral loads during treatment in the high-dose group compared with their baseline levels, and cessation of the therapy caused viral load rebound to the pretreatment levels. No significant difference (P = 0.06) was found in the plasma viral loads during treatment in the low-dose group. The CD4+ T cell counts and CD4/CD8 ratios remained at stable high levels during the treatment period. AKQ reduced plasma viral loads in the SHIV89.6-infected Chinese rhesus macaque model.