ABSTRACT
BACKGROUND: Schistosomiasis is a serious but neglected parasitic disease in humans that may lead to liver fibrosis and death. Activated hepatic stellate cells (HSCs) are the principal effectors that promote the accumulation of extracellular matrix (ECM) proteins during hepatic fibrosis. Aberrant microRNA-29 expression is involved in the development of fibrotic diseases. However, less is known about the role of miR-29 in Schistosoma japonicum (S. japonicum)-induced hepatic fibrosis. METHODS: The levels of microRNA-29a-3p (miR-29a-3p) and Roundabout homolog 1 (Robo1) were examined in liver tissues during S. japonicum infection. The possible involvement of the miR-29a-3p-Robo1 signaling pathway was determined. We used MIR29A conditional knock-in mice and mice injected with an miR-29a-3p agomir to investigate the role of miR-29a-3p in schistosomiasis-induced hepatic fibrosis. The functional contributions of miR-29a-3p-Robo1 signaling in liver fibrosis and HSC activation were investigated using primary mouse HSCs and the human HSC cell line LX-2. RESULTS: MiR-29a-3p was downregulated in humans and mice with schistosome-induced fibrosis, and Robo1 was upregulated in liver tissues. The miR-29a-3p targeted Robo1 and negatively regulated its expression. Additionally, the expression level of miR-29a-3p in schistosomiasis patients was highly correlated with the portal vein and spleen thickness diameter, which represent the severity of fibrosis. Furthermore, we demonstrated that efficient and sustained elevation of miR-29a-3p reversed schistosome-induced hepatic fibrosis. Notably, we showed that miR-29a-3p targeted Robo1 in HSCs to prevent the activation of HSCs during infection. CONCLUSIONS: Our results provide experimental and clinical evidence that the miR-29a-3p-Robo1 signaling pathway in HSCs plays an important role in the development of hepatic fibrosis. Therefore, our study highlights the potential of miR-29a-3p as a therapeutic intervention for schistosomiasis and other fibrotic diseases.
Subject(s)
MicroRNAs , Schistosoma japonicum , Schistosomiasis , Humans , Mice , Animals , Schistosoma japonicum/genetics , Schistosoma japonicum/metabolism , Hepatic Stellate Cells/metabolism , Nerve Tissue Proteins , MicroRNAs/genetics , MicroRNAs/metabolism , Receptors, Immunologic , Liver Cirrhosis/genetics , Liver Cirrhosis/prevention & control , Schistosomiasis/pathologyABSTRACT
BACKGROUND: Due to confounders like hyperglycemia, patients with type 2 diabetes mellitus (T2DM) have an increased susceptibility to venous thromboembolism (VTE). However, formal risk assessment models, such as using the Padua score, do not include all T2DM-associated risk factors for VTE. Therefore, this study aims to develop and validate a predictive nomogram for VTE in non-surgical inpatients with T2DM. METHODS: We retrospectively analyzed the clinical and biochemical data of 420 non-surgical inpatients with T2DM between 2017 and 2021 from three centers (the PLA 474th hospital, the Second Affiliated Hospital of Xinjiang Medical University and the Fifth Affiliated Hospital of Xinjiang Medical University). A multivariate analysis based on logistic regression model was performed to identify independent risk factors and construct a nomogram. The predictive values were compared by calculating the integrated discrimination improvement (IDI) and net reclassification improvement (NRI), and by decision curve analysis (DCA). RESULTS: Old age, BMI, D-dimer, hypoproteinemia, acute infection, acute myocardial infarction, cerebral ischemic stroke, reduced mobility, and heart/respiratory failure were independent risk factors for VTE in non-surgical inpatients with T2DM, as indicated by the multivariate analysis. The nomogram demonstrated superior discriminative ability compared to the Padua score (area under the curve: 0.923 vs. 0.849). NRI and IDI were also observed, and the DCA identified the greater net benefit and clinical utilization of the new nomogram. CONCLUSIONS: A predictive nomogram for VTE in non-surgical inpatients with T2DM was developed and validated in this study. The nomogram is highly predictive and easy to operate, but external data verification is required before it can be further used.
ABSTRACT
This article analyzed the quality control of 35 preparations with cortex moutan in volume I pharmacopoeia of People' s Republic of China (2005 edition). The result showed that only 11 preparations selected paeonol in cortex moutan as one of their quality indexes, the others selected other components or none as index. Via discussing problems on quality control in preparations with cortex moutan, it gave some suggestions on index selection for quality control and method selection for the determination of paeonol in preparations with cortex moutan, and provided some references for the revision of pharmacopoeia of People's Republic of China (2005 edition I ).
