Protective effect of borneol on the cutaneous toxicity of gilteritinib / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effect of borneol on cutaneous toxicity of gilteritinib and to explore possible compounds that can intervene with the cutaneous toxicity.@*METHODS@#C57BL/6J male mice were given gilteritinib by continuous gavage for 28 d and the damage to keratinocytes in the skin tissues was observed with hematoxylin and eosin (HE) staining, TUNEL assay and immunohistochemistry. Human keratinocytes HaCaT were treated with gilteritinib, and cell death and morphological changes were examined by SRB staining and microscopy; apoptosis of HaCaT cells was examined by Western blotting, flow cytometry with propidium iodide/AnnexinⅤ double staining and immunofluorescence; the accumulation of cellular reactive oxygen species (ROS) was examined by flow cytometry with DCFH-DA. Compounds that can effectively intervene the cutaneous toxicity of gilteritinib were screened from a natural compound library using SRB method, and the intervention effect of borneol on gilteritinib cutaneous toxicity was further investigated in HaCaT cells and C57BL/6J male mice.@*RESULTS@#In vivo studies showed pathological changes in the skin with apoptosis of keratinocytes in the stratum spinosum and stratum granulosum in the modeling group. Invitro studies showed apoptosis of HaCaT cells, significant up-regulation of cleaved poly (ADP-ribose) polymerase (c-PARP) and gamma-H2A histone family member X (γ-H2AX) levels, and increased accumulation of ROS in gilteritinib-modeled skin keratinocytes compared with controls. Screening of the natural compound library revealed that borneol showed excellent intervention effects on the death of HaCaT cells. In vitro, cell apoptosis was significantly reduced in the borneol+gilteritinib group compared to the gilteritinib control group. The levels of c-PARP, γ-H2AX and ROS in cells were significantly decreased. In vivo, borneol alleviated gilteritinib-induced skin pathological changes and skin cell apoptosis in mice.@*CONCLUSIONS@#Gilteritinib induces keratinocytes apoptosis by causing intracellular ROS accumulation, resulting in cutaneous toxicity. Borneol can ameliorate the cutaneous toxicity of gilteritinib by reducing the accumulation of ROS and apoptosis of keratinocytes in the skin tissue.

Crelational Research of the Level of Plasma Procalcitonin, Blood Lactic Acid and Endotoxin in Patients of Severe Pneumonia Complicated with Sepsis / 现代检验医学杂志

Objective To evaluate the clinical value of the level of plasma procalcitonin,blood lactic acid an1 endotoxin in patients of severe pneumonia complicated with sepsis.Methods The 40 cases of severe pneumonia complicated with sepsis(observation group)were analyzed retrospectively,they were divided into survival group included 20 cases and the death group included 20 cases.Meanwhile the 20 cases of healthy persons were selected as control group.The worst score of Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) within 24 hours after admission were record.The level of plasma procalcitonin,blood lactic acid and endotoxin were compared between three groups.In addition do a correlation study between the above indexes and the score of APACHE Ⅱ.Results The level of plasma Procalcitonin,blood lactic acid and endotoxin of observation group increased significantly compared with the control group [(0.02±0.01 ng/ml,0.87 ± 0.27 mmol/L,4.15±1.63 pg/ml) vs (18.29±11.02 ng/ml,6.55 ± 3.02 mmol/L and 15.5±10.38 pg/ml),t=10.48,11.79,6.75,all P＜0.05].The level of plasma procalcitonin,blood lactic acid and endotoxin of the death group increased significantly compared with the survival group [(9.52±2.93 ng/ml,4.26±1.78 mmol/L,7.62±3.04 pg/ml) vs (27.06±8.88 ng/ml,8.84± 2.14 mmol/L and 23.39± 9.00 pg/ml),t=8.39,7.35,7.42,all P＜0.05].In the all patients of severe pneumonia complicated with sepsis,there was positive correlation among plasma procalcitonin,blood lactic acid,endotoxin and the score of APACHE Ⅱ (r=0.919,P=0.001;r=0.914,P=0.002;r=0.909,P=0.004).Conclusion The level of plasma procalcitonin,blood lactic acid and endotoxin are very important indexes in assessment of the severity and the prognosis of severe pneumonia complicated with sepsis,that has important value in clinical application.

Clinical significance of serum hyaluranate in patients of uremia and kidney transplantation / 中华检验医学杂志

0.05)]. Conclusion The elevated serum HA is linked to a potential marker in kidney transplantation.