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OBJECTIVE: To construct a stable rat portal vein thrombosis (PVT) model and explore the time window of urokinase thrombolytic therapy on this basis. METHODS: Constructing a rat PVT model by combining anhydrous ethanol disruption of portal endothelium with stasis of blood flow. Forty-eight rats after PVT modeling were divided into control group and experimental group, with 24 rats in each group. The experimental and control groups were given urokinase treatment and saline tail vein injection, respectively. The two groups of rats were observed and compared for PVT formation at 1, 3 and 5 days after modeling, respectively. RESULTS: A stable rat PVT model was successfully constructed. No significant differences were found in PVT length, portal vein wet weight, and percentage of luminal occlusion area in the control rats at 1, 3, and 5 days after successful modeling (P > 0.05). Compared with control rats 1 day after modeling, the percentage of non-organized thrombus luminal area was significantly decreased (P < 0.0001), and the percentage of organized thrombus luminal area was significantly increased (P < 0.0001) in the PVTs of control rats at 3 and 5 days after modeling. After thrombolytic treatment with urokinase, plasma fibrinogen (FBG) levels were significantly decreased in the experimental group of rats compared with the control group (P < 0.0001), and plasma D-dimer (D2D) levels were significantly increased in the experimental group of rats compared with the control group (P < 0.0001). In addition, we observed prolongation of prothrombin time (PT) in the experimental group at 1, 3 and 5 days after modeling compared to the control group (P = 0.0001). Compared with the control group, portal vein wet weight and PVT length were significantly decreased in the experimental group of rats at 1 day after modeling (P < 0.05), whereas these differences were not found in the two groups of rats at 3 and 5 days after modeling (P > 0.05). The percentage of non-organized thrombus area in the experimental group was significantly decreased compared with that in the control group at 1, 3, and 5 days after modeling (P < 0.05), whereas there was no significant difference in the percentage of lumen area of organized thrombus between the two groups (P > 0.05). CONCLUSION: The method of producing a rat PVT model by destroying the endothelium of the portal vein by anhydrous ethanol combined with blood flow stasis is feasible and reproducible. In addition, the optimal time window for thrombolysis in the treatment of PVT in rats using urokinase is the early stage of thrombosis, when the fibrin content is highest.

Asunto(s)

Modelos Animales de Enfermedad , Vena Porta , Terapia Trombolítica , Activador de Plasminógeno de Tipo Uroquinasa , Trombosis de la Vena , Animales , Vena Porta/efectos de los fármacos , Trombosis de la Vena/tratamiento farmacológico , Ratas , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Terapia Trombolítica/métodos , Masculino , Ratas Sprague-Dawley , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo

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BACKGROUND: Immune Checkpoint Inhibitors (ICIs) are becoming a new treatment approach for patients with unresectable hepatocellular carcinoma (uHCC). However, the results regarding its efficacy compared with the standard regimen of targeted therapy are not consistent. AIMS: Our aim was to conduct a meta-analysis of existing studies to reveal the differences in the efficacy and safety of the two systems of treatment. METHODS: The related studies were searched in PubMed, Web of Science, the Cochrane Library, and Embase from inception to June 30th, 2022. Data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and rate of treatment- related adverse events (TrAEs) with their 95% confidence intervals (CI) were pooled and analyzed by Stata 12.0 software. RESULTS: A total of ten high-quality controlled clinical studies with 5,539 patients with uHCC were included. The hazard ratio (HR) of the OS and PFS were 0.80 (95% CI, 0.74-0.86) and 0.72 (95% CI, 0.58-0.89), respectively. In addition, the odds ratio (OR) of the ORR and DCR were 3.39 (95% CI, 2.75-4.17) and 1.20 (95% CI, 0.84-1.73), respectively. The ORR of ICIs monotherapy, ICIs plus anti-vascular endothelial growth factor (VEGF) and ICIs plus ICIs were 16% (95% CI, 0.13-0.18), 17% (95% CI, 0.10-0.27), and 20% (95% CI, 0.16-0.24), respectively. For all included studies, the OR of the overall TrAEs was 0.51(95% CI, 0.22-1.18), and grade ≥ 3 TrAEs was 0.78 (95% CI, 0.53-1.14). CONCLUSION: ICIs were more effective than targeted drugs concerning survival periods and ORR in patients with uHCC while maintaining a stable safety profile.

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BACKGROUND: For resectable hepatocellular carcinoma (HCC), radical hepatectomy is commonly used as a curative treatment. However, postoperative recurrence significantly diminishes the overall survival (OS) of HCC patients, especially with microvascular invasion (MVI) as an independent high-risk factor for recurrence. While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients, the specific role of adjuvant therapies in those with MVI remains unclear. AIM: To conduct a network meta-analysis (NMA) to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen. METHODS: A systematic literature search was conducted on PubMed, EMBASE, and Web of Science until April 6, 2023. Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included. Hazard ratios (HRs) with 95% confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA. RESULTS: Fourteen eligible trials (2268 patients) reporting five different therapies were included. In terms of reducing the risk of recurrence, radiotherapy (RT) [HR = 0.34 (0.23, 0.5); surface under the cumulative ranking curve (SUCRA) = 97.7%] was found to be the most effective adjuvant therapy, followed by hepatic artery infusion chemotherapy [HR = 0.52 (0.35, 0.76); SUCRA = 65.1%]. Regarding OS improvement, RT [HR: 0.35 (0.2, 0.61); SUCRA = 93.1%] demonstrated the highest effectiveness, followed by sorafenib [HR = 0.48 (0.32, 0.69); SUCRA = 70.9%]. CONCLUSION: Adjuvant therapy following hepatectomy may reduce the risk of recurrence and provide a survival benefit for HCC patients with MVI. RT appears to be the most effective adjuvant regimen.

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AIM: The aim of this study was to evaluate the efficacy and safety of the anticoagulants for the prevention of portal vein system thrombosis (PVST) in patients with cirrhosis after splenectomy and explore the optimal time of anticoagulant administration. METHODS: A systematic literature search was performed using PubMed, Embase and China Biology Medicine disc (CBM)databases, so as to screen out studies comparing the prognoses between cirrhotic post-splenectomy patients treated with and without anticoagulants. The parameters that were analyzed included the incidence of PVST and postoperative bleeding. RESULTS: With a total of 592 subjects, we included 8 studies (6 observational and 2 randomized trials) that fulfilled the inclusion criteria. We found that the incidence of PVST was significantly lower in the anticoagulation group during the first 6 months of anticoagulant administration. And the largest difference in the incidence of PVST between the anticoagulation and control groups was observed at 3 months (odds ratio 0.17(0.11~0.27); P = 0.767; I2 = 0.0%) and 6 months (OR = 0.21(0.11~0.40); P = 0.714; I2 = 0.0%) postoperatively. The incidence of bleeding was not significantly higher in the anticoagulation group (odds ratio 0.71 (0.30~1.71); P = 0.580; I2 = 0.0%). CONCLUSION: Low-molecular weight heparin (LMWH) and warfarin can decrease the incidence of PVST in post-splenectomy cirrhotic patients without an increased risk of bleeding. And the optimal use time of warfarin is 6 months after splenectomy.

Asunto(s)

Trombosis de la Vena , Warfarina , Humanos , Warfarina/uso terapéutico , Vena Porta/patología , Heparina de Bajo-Peso-Molecular , Esplenectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Trombosis de la Vena/etiología , Trombosis de la Vena/prevención & control , Trombosis de la Vena/epidemiología , Anticoagulantes/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía

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Neutrophil extracellular traps (NETs) as special release products of neutrophils have received extensive attention. They are composed of decondensed chromatin and coated with nucleoproteins, including histones and some granulosa proteins. NETs can form a network structure to effectively capture and eliminate pathogens and prevent their spread. Not only that, recent studies have shown that NETs also play an important role in venous thrombosis. This review provides the most important updated evidence regarding the mechanism of NETs formation and the role of NETs in the process of venous thrombosis. The potential prophylactic and therapeutic value of NETs in venous thrombotic disease will also be discussed.

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Beads trapped in optical tweezers are aligned along the optical propagation direction, which makes it difficult to determine the number of beads with bright-field microscopy. This problem also dramatically influences the measurement of the optical trapping based single-molecule force spectroscopy. Here, we propose a video processing approach to count the number of trapped micro-objects in real time. The approach uses a normalized cross-correlation algorithm and image enhancement techniques to amplify a slight change of the image induced by the entry of an exotic object. As tested, this method introduces a ∼10% change per bead to the image similarity, and up to four beads, one-by-one falling into the trap, are identified. Moreover, the feasibility of the above analysis in a moving trap is investigated. A movement of the trap leads to a fluctuation of less than 2% for the similarity signal and can be ignored in most cases. The experimental results prove that image similarity measurement is a sensitive way to monitor the interruption, which is very useful, especially during experiments. In addition, the approach is easy to apply to an existing optical tweezers system.