Risk Factors for Rebleeding After Endoscopic Injection of Cyanoacrylate Glue for Gastric Varices: A Systematic Review and Meta-Analysis.

BACKGROUND: Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients. AIM: This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding. METHODS: Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included. RESULTS: The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100%. The pooled rate of gastric varices recurrence was 34% [95% CI 21-46, I2 = 61.4%], early rebleeding rate was 16% [95% CI 11-20, I2 = 37.4%], late rebleeding rate was 39% [95% CI 36-42, I2 = 90.9%], mild and moderate adverse events rate were 28% [95% CI 24-31, I2 = 91.6%], 3% [95% CI - 2 to 8, I2 = 15.3%], rebleeding-related mortality rate was 6% [95% CI 2-10, I2 = 0%], all-cause mortality rate was 17% [95% CI 12-22, I2 = 63.6%]. Independent risk factors for gastric variceal rebleeding included portal venous thrombosis, ascites, cyanoacrylate volume, fever/systemic inflammatory response syndrome, red Wale sign, previous history of variceal bleeding, active bleeding and paragastric veins. The use of proton pump inhibitors could be a protective factor. CONCLUSIONS: Endoscopic cyanoacrylate glue injection is an effective and safe treatment for gastric varices. Cirrhotic patients with the above risk factors may benefit from treatment aimed at reducing portal hypertension, antibiotic prophylaxis, and anticoagulation if they meet the indications.

CellBiAge: Improved single-cell age classification using data binarization.

Aging is a major risk factor for many diseases. Accurate methods for predicting age in specific cell types are essential to understand the heterogeneity of aging and to assess rejuvenation strategies. However, classifying organismal age at single-cell resolution using transcriptomics is challenging due to sparsity and noise. Here, we developed CellBiAge, a robust and easy-to-implement machine learning pipeline, to classify the age of single cells in the mouse brain using single-cell transcriptomics. We show that binarization of gene expression values for the top highly variable genes significantly improved test performance across different models, techniques, sexes, and brain regions, with potential age-related genes identified for model prediction. Additionally, we demonstrate CellBiAge's ability to capture exercise-induced rejuvenation in neural stem cells. This study provides a broadly applicable approach for robust classification of organismal age of single cells in the mouse brain, which may aid in understanding the aging process and evaluating rejuvenation methods.

Reactive Oxygen Species Induce Endothelial Differentiation of Liver Cancer Stem-Like Sphere Cells through the Activation of Akt/IKK Signaling Pathway.

Cancer stem cells (CSCs) from various cancers are able to transdifferentiate into endothelial cells and further form functional blood vessels, indicating another possible resistance mechanism to antiangiogenic agents. However, it remains unclear whether CSCs from hepatocellular carcinoma have the ability to differentiate into endothelial cells, and thus resulting in resistance to antiangiogenic therapy targeting VEGF. Reactive oxygen species (ROS) are involved in the self-renewal and differentiation of CSCs, yet, their role in endothelial differentiation of CSCs has been poorly understood. In this study, we found that cancer stem-like sphere cells enriched from human hepatocellular carcinoma cell line Hep G2 could differentiate into endothelial cells morphologically and functionally, and this process could be blocked by Akt1/2 kinase inhibitor and IKK-ß inhibitor BAY 11-7082 but not by Bevacizumab, a VEGFA-binding antibody, and DAPT, a γ-secretase inhibitor. Both hydrogen peroxide and BSO (an inhibitor of GSH biosynthesis) induce the differentiation of cancer stem-like sphere cells into endothelial cells, which can be canceled by the antioxidant N-Acetyl-L-cysteine (NAC). We also found that hydrogen peroxide or BSO induces the phosphorylation of Akt and IKK of endothelial differentiated sphere cells. Accordingly, both Akt1/2 kinase inhibitor and BAY 11-7082 inhibited hydrogen peroxide and BSO-mediated endothelial differentiation of cancer stem-like sphere cells. Collectively, the results of the present study demonstrate that cancer stem-like sphere cells from Hep G2 are able to differentiate into endothelial cells both morphologically and functionally, and this process is independent of VEGF and NOTCH signaling but dependent on the activation of Akt and IKK. ROS promote endothelial differentiation of cancer stem-like sphere cells through activation of Akt/IKK signaling pathway. Therefore, our study reveals a novel mechanism of resistance to conventional antiangiogenic therapy and may provide a potential therapeutic target for liver cancer treatment.