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Objective:To investigate the effects of triptolide (TPL) and BET protein inhibitor JQ1 on proliferation inhibition and apoptosis induction of MLL-rearranged acute myeloid leukemia (AML) cell line MV4-11, and to explore their synergistic mechanisms.Methods:MV4-11 cells in logarithmic growth phase were treated with different concentrations (100, 200, 300, and 400 nmol/L) of JQ1, 4 nmol/L TPL or different concentrations of JQ1 combined with 4 nmol/L TPL for 48 h. Cell proliferation was detected by CCK-8 method, apoptosis was detected by flow cytometry (FCM), mitochondrial membrane potential was detected by JC-1 method, and expressions of mitochondrial apoptosis pathway-related proteins were detected by Western blot.Results:The 50% inhibitory concentration ( IC50) value of MV4-11 cells treated with JQ1 for 48 h was (283.9±10.7) nmol/L. However, 4 nmol/L TPL significantly enhanced the inhibitory effect of JQ1 on proliferation of MV4-11 cells, the IC50 value of MV4-11 cells treated with JQ1 combined with TPL was (148.1±2.6) nmol/L, and the difference was statistically significant ( t = 25.31, P = 0.029). The result of FCM assay showed that compared with the JQ1 alone group [(9.6±2.3)%, (12.6±1.4)%, (19.5±3.3)%, and (22.7±2.1)%], 4 nmol/L TPL combined with different concentrations (100, 200, 300, and 400 nmol/L) of JQ1 acted on MV4-11 cells for 48 h, the proportions of apoptotic cells were (16.4±1.9)%, (27.5±2.1)%, (32.9±3.6)%, and (35.5±3.0)%, respectively, the difference was statistically significant ( F = 9.25, P < 0.01). After treated with 4 nmol/L TPL and JQ1 for 12 h, the level of cell membrane potential in MV4-11 cells was significantly lower than that of JQ1 single agent group, and the difference was statistically significant ( P < 0.05). After treated by 4 nmol/L TPL combined with JQ1 for 24 h, the levels of anti-apoptotic proteins bcl-2 and Mcl-1 decreased, and the level of pro-apoptotic protein bax increased. Conclusion:TPL can significantly enhance the proliferation inhibition and apoptosis induction effects of BET protein inhibitor JQ1 on MLL-rearranged AML cells, and the mechanism may be related to enhancing the mitochondrial apoptosis pathway.
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Objective:To explore the feasibility and clinical efficacy of gelatin sponge packing in reducing bone cement leakage in percutaneous kyphoplasty (PKP).Methods:A retrospective case-control study was conducted in data of 171 patients (171 vertebrae) with monosegmental lumbar osteoporosis compressive fracture treated by PKP from January 2015 to December 2018 in Sichuan Orthopedic Hospital. There were 66 males and 105 females, with the age of (67.9±6.7)years (range, 60-87 years). There were 22 patients with T 10 fracture, 28 with T 11 fracture, 37 with T 12 fracture, 34 with L 1 fracture, 32 with L 2 fracture and 18 with L 3 fracture. A total of 80 patients were pre-filled with gelatin sponge before injection (Group A), and 91 patients were not filled with gelatin sponge before injection (Group B). The operation time, amount of bone cement, and rate of bone cement leakage were recorded. The change of anterior vertebral height, Cobb angle, visual simulation score (VAS) and Oswestry disability index (ODI) were compared before operation and at postoperative 1 day, 3 months, 6 months, 12 months. Results:All patients were followed up for 1-12 months [(12.8±0.6)months]. The operation time in Group A and B was (48.3±1.2)minutes and (42.3±1.3)minutes ( P<0.05). The amount of bone cement in Group A and B was (5.4±0.8)ml and (5.6±0.7)ml ( P>0.05). The incidence of bone cement leakage in Group A and B was 11% (9/80) and 26% (24/91) ( P<0.05). There was no significant difference between the two groups in the anterior height of injured vertebrae, change of Cobb angle, VAS and ODI before and after operation ( P>0.05). Conclusion:Gelatin sponge can reduce the rate of bone cement leakage in PKP for the treatment of thoracolumbar osteoporosis compressive fracture, and has similar effect with PKP in correcting kyphosis, alleviating pain and improving life quality.
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Objective To investigate the clinical significance of biochemical markers in EBC and serum in patients with bronchial asthma and chronic obstructive pulmonary disease overlap syndrome(ACOS). Methods We selected Patients with chronic airway inflammatory diseases in our hospital,These patients underwent clinical trial after the stable phase,including 18 ACOS patients,22 asthma patients,24 COPD patients and 20 healthy non-smokers in the same period.8-isoPG and other inflammatory factors levels in EBC and serum were measured in the selected patients. A comparative analysis was performed. Results The levels of EBC 8-isoPG in the ACOS group were significantly higher than those in the healthy control group,The levels of serum and EBC 8-isoPG in the ACOS group were significantly higher than the asthma group and the COPD group(P < 0.05). The level of 8-isoPG in EBC was not related to age,smoking index,weight,and FEV1value(P>0.05).Conclusions Inflam-matory factors including 8-isoPG,are involved in chronic inflammation in lung tissues of patients with ACOS. 8-isoPG in EBC may have potential value in identifying ACOS from COPD and asthma as biomarkers and deserve further study.
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BACKGROUND: As a minimally invasive technology, percutaneous vertebroplasty is a safe and effective treatment for osteoporotic vertebral compression fractures.OBJECTIVE: To overview the research progress concerning the biomechanical properties, bone strength maintenance, bone absorption and degradation of bone filling materials used in percutaneous vertebroplasty.METHODS: The first author conducted a computer-based retrieval of CNKI, PubMed and Medline databases for relevant articles published from January 2005 to May 2016. The keywords were bone cement, bone filling materials, percutaneous vertebroplasty in English and Chinese, respectively.RESULTS AND CONCLUSION: Polymethyl methacrylate is not an ideal material for osteoporotic vertebral compression fractures. Calcium phosphate cement and calcium sulfate cement can replace the traditional polymethyl methacrylate; however, some problems still exist, such as poor effect of venography, incontrollable biological degradation rate, and lack of the evidence-based medicine about its long-term effect. Composite bone cement, as a good bone repair material, holds the advantages of various bone cements. As the composite bone cement has just been introduced in clinical practice, its long-term curative efficacy needs to be further studied.
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Objective To investigate whether exosome-derived microRNA of nasopharyngeal carcinoma suppresses apoptosis of tumor associated macrophage (TAM).Methods Target microRNAs and genes were determined by bioinformatics methods.Isolated exosomes were used to detect miR-20a expression by qRT-PCR.Furthermore,apoptosis index and proteins involved in apoptotic pathways were detected after miR-20a mimic and inhibitor transfection into macrophages.Results miR-20a expression was upregulated in isolated exosomes.miR-20a target gene was BCL2L11.MiR-20a overexpression could inhibit apoptosis of macrophages,meanwhile,apoptotic pathways related proteins Bim,caspase-9 and caspase-3 were significantly suppressed by miR-20a mimic(P＜0.05).Condusion miR-20a can suppress activation of Bim-caspase-9-casepase-3 and resulting in apoptotic inhibition of macrophages.
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It showed that the distribution of examination score was Gaussian distribution,the average score was 74.4,the paper reliability was 0.81,the difficult coefficient was 0.74 by analyzing and evaluating the quality of the examination paper of pharmacology from 2002 seven-year medical students in Central South University.Some objective questions are too difficult,while some subjective questions are too easy.According to the results of analysis,we think it better to culture the student's multi-ability in analyzing and solving questions by increasing the proportion of subjective question with some difficult coefficient and improving the teaching methods in future teaching.
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OBJECTIVE:To study the protctive effect of ginkgo biloba extractEGBon the kindey in the case of is?chemia-reperfusion injury.METHODS:The model of renal ischemia-reperfusion injury in male rats was made by ligation of left renal artery for40min and3h of reperfusion.The rats with pretreatment were fed with EGB at different doses prior to operation.The content of malonadialdihydeMDA,the activity of superoxide dismutaseSODin renal cortex and the levels of blood urea nitrogenBUN,creatinineCrin plasma were measured.The pathological changes of renal tissues were observed by electron microscope.RESULTS:After ischemia-reperfusion,the activity of SOD in renal cortex was decreased,however,the content of MDA in renal cortex and the levels of BUN,Cr in plasma were increased.Pathological changes induced by ischemia-reperfusion in renal tissues were observed clearly.The pretreatment of rats with EGB significantly prevented reduction of SOD activity and increase of MDA content in renal cortex,decreased elevation of concentration of BUN and Cr in plas?ma.Pathological changes of proximal tubular cells in rat kidneys induced by ischemia-reperfusion were also prevented by the pretreatment with EGB.CONCLUSION:EGB can protect rats from renal injuries caused by ischemia-reperfusion.The mechanism of protective effects of EGB may be related to preserving the activity of SOD and alleviating lipid peroxidation.
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Objective To observe the stability and the change pattern of VEGF expression in myocardium in varied postmortem periods,and to evaluate its usefulness in diagnosis of early myocardial ischemia after death.Methods An animal model of early myocardial ischemia was established by ligating coronary artery of rabbit,immunohistochemistry(SP protocol),image analysis technique and statistical analysis system are applied to detect and compare the area and intensity of expression of VEGF in cardiocytes,and its stability in different postmortem perieds.ResultsIn ischemic myocardium,VEGF shows foci or sheets of intense positive staining in cardiocytes,with negative or weak staining in some cells.There was weak staining in vascular endothelial cells and smooth muscle cells,but no staining in interstitium.When ischemic myocardium stored at 4℃,the staining of VEGF became weaker with time delay,but there was weak staining in a fraction of cardiocytes even 10d after death.There was significant difference in the intensity of VEGF staining between ischemic and normal postmortem myocardium from 1 to 10d.Conclusion VEGF can withstand a certain degree of autolysis or putrefaction,and the immunohistochemical staining of it is valuable in the diagnosis of early myocardial ischemia in corpses stored at 4℃ for 1~10d after death.