Keshan disease was an endemic cardiomyopathy in China. The very low selenium intake of local people was considered to be an important causal factor. The main pathological characteristics of this disease was multifo-cal necrosis and fibrous replacement of myocardium that was scattered throughout the wall of all chambers.Two patterns of myocardial necrosis, myofibrillar pattern and mitochondrial pattern were distinguished in electron microscopy. The myofibrillar pattern was characterized by myofibril segmentation. It agreed well with the contraction band necrosis described in light microscopy. It was mainly seen in acute Keshan heart and might be related to circulatory disorders. Mitochondrial pattern was identical with myocytolysis of conventional pathology. It represented the typical lesion of Keshan disease.Mitochondria showed early and conspicuous changes in involved myo-cytes. Myofibrillar damage seemed to be secondary to the mitochondrial injury in the development of myocytolysis.Histochemical studies revealed that the acid phosphatase activity was obviously increased in muscle fibers surrounding the necrotic foci, and the succinic dehydrogenase activity was greatly reduced in damaged myocardio-cytes.

Objective:To evaluate the effect of dexmedetomidine (Dex) on the proliferation, migration and invasion ability of renal carcinoma cells and the relationship with ferroptosis.Methods:Experiment Ⅰ GRC-1 cells at the logarithmic growth phase were selected and divided into 5 groups ( n=6 each) using a random number table method: control group (group C) and different concentrations of dexmedetomidine groups(D1, D2, D3, and D4 groups). Group C was routinely incubated for 24 h. D1, D2, D3, and D4 groups were incubated with dexmedetomidine at 0.1, 1.0, 10.0 and 100.0 μmol/L respectively, for 24 h. The cell proliferation ability was assessed by CCK-8 assay.The cell migration and invasion ability was was evaluated by Transwell chamber assay. Experiment Ⅱ GRC-1 cells at the logarithmic growth phasewere selected and divided into 3 groups ( n=6 each) using a random number table method: control group (group C), dexmedetomidine group (group D), and dexmedetomidine+ Ferrostatin-1 group (group D+ F). Group C was routinely cultured for 24 h. Dexmedetomidine 10 μmol/L was added and cells were incubated for 24 h in group D. Dexmedetomidine 10 μmol/L was added, Ferrostatin-1 1 μmol/L was simultaneously added, and then cells were incubated for 24 h in group D+ F. The proliferation ability of the cells was tested by CCK-8 assay, and the migration and invasion ability of the cells was detected by Transwell assay. The contents of glutathione (GSH), malondialdehyde (MDA) and Fe 2+ were measured by the colorimetric method. The expression of glutathione peroxidase 4(GPX4) and ATF4-induced solute carrier family 7a member 11 (SLC7A11) was detected by Western blot. Results:Experiment I Compared with group C, the cell proliferation and the number of migrating and invading cells were significantly decreased in D3 and D4 groups ( P<0.05), and no significant change was found in aforementioned indexes in D1 and D2 groups ( P>0.05). Experiment Ⅱ Compared with group C, the cell proliferation and the number of migrating and invading cells were significantly decreased, the content of Fe 2+ was increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated ( P<0.05), and no significant change was found in MDA content in group D( P>0.05). Compared with group D, the cell proliferation and the number of migrating and invading cells were significantly increased, the content of Fe 2+ was decreased, the content of GSH was increased, the expression of GPX4 and SLC7A11 was up-regulated ( P<0.05), and no significant change was found in the MDA content in group D+ F( P>0.05). Conclusions:Dexmedetomidine can inhibit the proliferation, migration and invision ability of renal carcinoma cells, and the mechanism is related to promotion of ferroptosis.