Cholesterol-associated lysosomal disorder triggers cell death of hematological malignancy: Dynamic analysis on cytotoxic effects of LW-218

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth

Study on the establishment of clinical nursing pathway for elderly patients with acute chest pain in emergency department / 中国实用护理杂志

Objective:To construct a reasonable and efficient clinical nursing pathway for elderly patients with acute chest pain in the emergency department, and to provide a standardized and rapid treatment process for such patients.Methods:Through literature review and theoretical analysis, the basic framework of clinical nursing pathway was preliminarily drawn up. Twenty one clinical medical and nursing experts from all over the country were selected to conduct two rounds of expert consultation with Delphi method, and the clinical nursing path was finally determined.Results:The recovery rates of the two rounds of questionnaires were 100.00% and 95.24%, and the rates of submission expert suggestions were 61.90% and 45.00%, the authority coefficients of experts were 0.85 and 0.88, and the coordination coefficients were 0.23 and 0.30. Finally, the clinical nursing pathway was constructed after two rounds of consultation.Conclusion:The positive coefficient and authority coefficient of the two rounds of experts were both high, and the variable coefficient and coordination coefficient were in line with the statistical requirements, so the clinical nursing path of the elderly patients with acute chest pain had high scientificity and reliability.