ABSTRACT
The air at high altitude is thin and belongs to the environment of low temperature, low oxygen and low pressure. The human brain is the most sensitive to hypoxia. Hypoxia will cause dysfunction of the central nervous system, resulting in high-altitude hypoxic brain injury, including mild high altitude headache and more destructive high altitude cerebral edema (HACE). Recently, with more and more people work and live in high altitude areas, the development of high-altitude hypoxic brain injury drugs would produce great economic value and social significance. Non clinical pharmacodynamic evaluation is the basic of drug development, which plays a key role in improving the success rate of clinical transformation and reducing the risk of clinical research. This review summarizes the cell models and animal models, and the evaluation indicators usually used to explore the candidates of high-altitude hypoxic brain injury. We aim at establishing a standardized non clinical efficacy evaluation system for high altitude hypoxic encephalopathy, and provide a standardized reference for drug development in hypoxic encephalopathy at high altitude at nonclinical stage.
ABSTRACT
Purpose To observe the expressions of LC3, NY-ES0-2, MAGE-D4, CD4+, CD8+, CD68+ in colorectal cancer and normal tissues and analysis the correlation of autophagy related gene LC3 and tumor surface antigen NY-ES0-2, MAGE-D4, immune cells CD4+, CD8+, CD68 +. To investigate the effect of the change of autophagy on immune cells function and its clinical significance. Methods Immunohistochemistry and Western blot were used to detect the expressions of LC3, NY-ESO-2, MAGE-D4, CD4, CD8, CD68 in 128 cases of colorectal cancer and normal tissues. The correlation among each factors and the patients' clinicopathological features were analyzed. Results (1 ) The expression of LC3 in colorectal cancer tissue was higher than in normal tissues. The expression of NY-ESO-2 was low while the expression of MAGE-D4 was high in colorectal cancer and both almost not express in normal tissues(P＜0.05). The infiltration of CD4+, CD8 +, CD68+ immune cells in colorectal cancer were higher than in normal tissues(P＜0.05). (2)The expression of LC3 protein in colorectal cancer was correlated positively with the expressions of tumor surface antigen NY-ESO-2, MAGE-D4 protein and the infiltration of CD8 +, CD68 + immune cells (P＜ 0.05 ), but had no correlation with the infiltration of CD4 + immune cells (P＞0.05). (3 ) The expression of NY-ESO-2 was correlated positively with the infiltration of CD4+, CD8 +, CD68 + immune cells. The expression of MAGE-D4 was correlated positively with the infiltration of CD8 +, CD68+ immune cells. (4) The expressions of NY-ESO-2, MAGE-D4, the infiltration of CD4+, CD8 + immune cells and lymph node metastasis were negatively correlated (P＜0.05). The expressions of NY-ESO-2, MAGE-D4, the infiltration of CD4+, CD8+ immune cells and TNM stage were negatively correlated (P＜ 0.05). The infiltration of CD8 + immune cells and grade was positively correlated (P＜0.05). Conclusion The expression of autophagy-related gene LC3 was related to the expressions of tumor surface antigen NY-ESO-2, MAGE-D4 and the infiltration of immune cells CD8 + and CD68+ in colorectal cancer. Therefore the autophagy key factor LC3 may participate in the immune of colorectal cancer.