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Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Assuntos
Camundongos , Animais , Hipóxia , Estresse Oxidativo , Autofagia , Cognição , Sirolimo/uso terapêuticoRESUMO
Objective:To investigate the attitude of neonatologists toward the treatment of extremely preterm infants (EPIs) in China.Methods:A cross-sectional survey was conducted using a questionnaire designed and posted on Wenjuanxing, a web-based survey platform, from June to July 2021. The respondents were neonatal physicians in various provinces and cities in China. The questionnaire covered the basic information, treatment experience and attitude towards EPIs, and opinions on the current definition of the preterm infant in China. The results were described or analyzed using the Chi-square test.Results:A total of 1 066 valid replies were collected. The respondents included 322 males and 744 females, among whom 78.1% (832/1 066) were assistant director physicians or director physicians, 82.8% (882/1 066) were from tertiary hospitals, and 83.0% (885/1 066) had the experiences of treating EPIs. In terms of the attitude toward the treatment of EPIs, 63.0% (672/1 066) of the respondents suggested that the lower limit of gestational age for EPIs requiring active resuscitation should be defined at 25 gestational weeks or less. Moreover, 57.1% (609/1 066) considered that the current domestic definition of preterm infants as 28 gestational age or above was inappropriate, and 75.2% (458/609) considered that the lower limit defined as preterm infants should be 25 gestational weeks or less. Concerning the treatment experience in EPIs, 54.3% (579/1 066) of the respondents suggested that in their hospital, withdrawing treatment in EPIs was common or very common, and 83.3% (888/1 066) considered that the main reason for withdrawing treatment was family members' concerns about the prognosis. Those who hesitated about treating the EPIs accounted for 71.6% (763/1 066), and 83.9% (640/763) hesitated due to the poor prognosis and possible medical disputes. Moreover, 32.7% (349/1 066) of the respondents or their colleagues had been involved in medical disputes about whether to treat EPIs, and 74.8% (797/1 066) believed that the patients should be the decision-maker on whether to treat EPIs or not.Conclusion:Most neonatal physicians in this survey hold a positive attitude toward the treatment of EPIs and believe that the lower limit of gestational age for preterm infants should be lowered. However, a hesitating attitude to the care of EPIs is still common, and uncertainty about the prognosis of EPIs remains a concern.
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Objective To evaluate the clinical application of preoperative multi-slice computed tomography (MSCT) and multi-slice computed tomography portography (MSCTP) in performing transjugular intrahepatic portosystemic stent shunt (TIPSS) combined with gastric coronary vein embolization (GCVE). Methods A total of 126 patients with cirrhosis complicated by upper gastrointestinal bleeding or massive ascites due to portal hypertension were enrolled in this study. The patients were arranged to receive TIPSS together with GCVE. Before the treatment, MSCT and MSCTP were performed in all patients. By using post-processing techniques, including maximum intensity projection (MIP), multiplanar reformation (MPR), volume rendering (VR) and surface shade display (SSD), the anatomy of liver was comprehensively evaluated. Results Both MSCT and MSCTP could clearly display morphologic changes of liver , the spatial relationship of the portal and hepatic veins , the degree and extent of portal collateral circulation , and the severity of ascites, which provided important anatomical information for preoperative evaluation of TIPSS and GCVE. Conclusion MSCT and MSCTP are non-invasive and reliable examinations for the diagnosis of cirrhosis with portal hypertension, it can further clarify the diagnosis and guide the performance of TIPSS and GCVE.
RESUMO
Objective To evaluate the clinical application of preoperative multi-slice computed tomography (MSCT) and multi-slice computed tomography portography (MSCTP) in performing transjugular intrahepatic portosystemic stent shunt (TIPSS) combined with gastric coronary vein embolization (GCVE). Methods A total of 126 patients with cirrhosis complicated by upper gastrointestinal bleeding or massive ascites due to portal hypertension were enrolled in this study. The patients were arranged to receive TIPSS together with GCVE. Before the treatment, MSCT and MSCTP were performed in all patients. By using post-processing techniques, including maximum intensity projection (MIP), multiplanar reformation (MPR), volume rendering (VR) and surface shade display (SSD), the anatomy of liver was comprehensively evaluated. Results Both MSCT and MSCTP could clearly display morphologic changes of liver , the spatial relationship of the portal and hepatic veins , the degree and extent of portal collateral circulation , and the severity of ascites, which provided important anatomical information for preoperative evaluation of TIPSS and GCVE. Conclusion MSCT and MSCTP are non-invasive and reliable examinations for the diagnosis of cirrhosis with portal hypertension, it can further clarify the diagnosis and guide the performance of TIPSS and GCVE.