ABSTRACT
Background: Liver cancer is one of the malignant tumors worldwide, while the prevention and control situation is grim at present, and the diffusion of its early screening technology still faces some challenges. This study aims to investigate the influencing mechanism of perceived ease of use, organizational support mechanism, and industry competitive pressure on hepatic early screening technologies use by physicians, so as to promote the wider use of corresponding technologies. Methods: Under the theoretical guidance of technology-organization-environment framework and mindsponge theory, this study took hepatic contrast-enhanced ultrasound as an example, and conducted a cross-sectional questionnaire by randomly selecting physicians from Fujian and Jiangxi provinces in China with a high and low incidence of liver cancer, respectively. Structural equation modeling was used to determine the correlation among perceived ease of use, organizational support mechanism, and industry competitive pressure, as well as their impact on the physicians' behavior toward contrast-enhanced ultrasound use. Results: The hypothesis model fits well with the data (χ2/df = 1.863, GFI = 0.937, AGFI = 0.908, RMSEA = 0.054, NFI = 0.959, IFI = 0.980, CFI = 0.980). Under technology-organization-environment framework, the perceived ease of use (ß = 0.171, p < 0.05), organizational support mechanism (ß = 0.423, p < 0.01), industry competitive pressure (ß = 0.159, p < 0.05) significantly influenced physicians' use of hepatic contrast-enhanced ultrasound. Besides, perceived ease of use and organizational support mechanism (ß = 0.216, p < 0.01), perceived ease of use and industry competitive pressure (ß = 0.671, p < 0.01), organizational support mechanism and industry competitive pressure (ß = 0.330, p < 0.01) were all associated significantly. Conclusion: From the lens of information processing (mindsponge theory) and technology-organization-environment framework, this study clarified the social and psychological influencing mechanism of perceived ease of use, organizational support mechanism, and industry competitive pressure on physicians' use of hepatic contrast-enhanced ultrasound. The results will directly propose recommendations for expanding hepatic contrast-enhanced ultrasound utilization and indirectly promoting other appropriate and effective health technologies diffusion within the integrated health system.
Subject(s)
Liver Neoplasms , Physicians , Humans , Early Detection of Cancer , Cross-Sectional StudiesABSTRACT
Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.
Subject(s)
Carcinoma, Hepatocellular , Hyperoxia , Liver Neoplasms , Selenium Compounds , Selenium , Animals , Mice , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Selenium/pharmacology , Selenium/therapeutic use , Selenium Compounds/metabolism , Selenium Compounds/pharmacology , Selenium Compounds/therapeutic use , Hydrogen Peroxide/pharmacology , Signal Transduction , Apoptosis , Hypoxia , Oxygen , Tumor MicroenvironmentABSTRACT
Background: Promoting technology diffusion and utilization is a key measure to address the great disparity in technical capacity within integrated health systems. However, even the effectiveness and appropriateness regarding technology has been widely recognized, its diffusion and utilization are still stagnant. The mechanisms that influence the technology from being recognized to being widely applied in practice remain largely unknown. Purpose: Taking hepatic contrast-enhanced ultrasound (CEUS) as an example, this study aimed to investigate the comprehensive influencing mechanism of organizational atmosphere and organizational practice on the knowledge, attitude, and practice toward diffusion and utilization of hepatic CEUS in the medical alliance. Methods: Based on the integration of organizational ready for change (ORC) and knowledge-attitude-practice (KAP), a structured questionnaire was developed. A multistage random sampling method was applied to investigate physicians who directly use CEUS working at the liver disease-related departments of sampled health institutions. Structural equation modeling (SEM) was used to verify the proposed hypotheses, and determine the relationship between the factors. Results: In total, 292 physicians were included. SEM results demonstrated that knowledge influenced both attitude and practice, while attitude positively predicted practice. Organizational practice and organizational atmosphere associated positively with each other. Organizational atmosphere positively affected the physicians' attitude toward CEUS diffusion and utilization (ß = 0.425, p < 0.001), while organizational practice positively affected corresponding knowledge (ß = 0.423, p < 0.001) and practice (ß = 0.275, p < 0.001). Additionally, there was a partial mediating effect between organizational practice and physicians' CEUS diffusion and utilization behavior. Conclusion: By verifying the influencing mechanism of organizational atmosphere and organizational practice on the physicians' KAP of hepatic CEUS diffusion and utilization, this study benefit tailoring strategies for promoting technology diffusion and utilization within medical alliance. It is recommended to develop an organizational atmosphere of advocating technology innovation, establish organizational support mechanism (SM) with multiple concrete supporting countermeasures, and so on.
Subject(s)
Health Knowledge, Attitudes, Practice , Liver/diagnostic imaging , Physicians , Ultrasonography , Atmosphere , Contrast Media , Humans , Surveys and QuestionnairesABSTRACT
We conceptually demonstrate single-cell infrared phenomics as a novel strategy of phenotypic screening with infrared microspectroscopy. Based on this development, the cancer cell HepG2 glycocalyx was first identified as a potential target of protopanaxadiol, an herbal medicine. These findings provide a powerful tool to accurately evaluate the cell stress response and to largely expand the phenotypic screening toolkit for drug discovery.
Subject(s)
Glycocalyx/genetics , Phenomics , Single-Cell Analysis , Hep G2 Cells , Humans , Phenotype , Spectrophotometry, InfraredABSTRACT
In the pathogenesis of acute respiratory distress syndrome (ARDS), an increase in vascular endothelial permeability may trigger pulmonary edema and ultimately lead to respiratory failure. Endothelial glycocalyx damage is an important factor that causes an increase in vascular endothelial permeability. Berberine (BBR) is an isoquinoline alkaloid extracted from Coptis chinensis, a plant used in traditional Chinese medicine that exerts multiple pharmacological effects. In this study, pretreatment with BBR inhibited the increase in vascular endothelial permeability in mice with lipopolysaccharide (LPS)-induced ARDS. BBR pretreatment inhibited the shedding of syndecan-1 (SDC-1) and heparan sulfate (HS), which are important components of the endothelial glycocalyx that lessen endothelial glycocalyx damage. BBR further significantly inhibited increases in important endothelial glycocalyx damage factors, including reactive oxygen species (ROS), heparanase (HPA), and matrix metalloproteinase 9 (MMP9) in LPS-induced ARDS mice and in LPS-stimulated human umbilical vein endothelial cells. BBR pretreatment also decreased the production of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and inhibited NF-κB signaling pathway activation in LPS-induced ARDS. In addition, BBR promoted the recovery of SDC-1 and HS content in injured endothelial glycocalyx after LPS treatment and accelerated its restoration. This is the first report of BBR maintaining the integrity of endothelial glycocalyx. These results provide a new theoretical basis for the use of BBR in the treatment of ARDS and other diseases related to endothelial glycocalyx damage.