PBRM1 loss promotes PD-L1 secretion in renal cell carcinoma cells through TNF-α/exosome signaling axis / 现代泌尿外科杂志

【Objective】 To explore the expressions of PBRM1 and PD-L1 in renal cell carcinoma (RCC), and the molecular mechanism of PBRM1 regulating PD-L1, in order to provide experimental results for clinical immunotherapy. 【Methods】 The protein expressions of PBRM1 and PD-L1 were detected with immunohistochemistry, and their mRNA expressions were determined by analyzing TCGA database. Meanwhile, the relationship between overall survival and mRNA expressions of PBRM1 and PD-L1 were analyzed in TCGA database. The exosomes were extracted with exoEasy Maxi Kit. Expressions of exosomal biomarkers CD63 and CD9 were detected with Western blotting, and their morphology was observed with transmission electron microscope. PD-L1 expression after IFN-γ, IL-6 and TNF-α treatment was detected with Western blotting. 【Results】 The expression of PBRM1 was significantly lower in canver tissue than in paracancerous tissue (P<0.001). The loss rate of PBRM1 was up to 76.4%. PBRM1 expression was not correlated with PD-L1 expression. PBRM1 deletion activated TNF-α/exosome signaling pathway, leading to increase of PD-L1 secretion in exosomes, which was then transported to the outside of cells. 【Conclusion】 There is no relationship between PBRM1 and PD-L1 protein expressions in RCC. However, PBRM1 mutation can lead to inflammatory signaling pathway activation, inducing PD-L1 secretion, which is encapsulated in exosomes and transported to the outside of cells, and affects the response of immunotherapy.

Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids / 中国药科大学学报

In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine ( TMP) /chalcone hybrids ( 2-26) were synthesized and evaluated based on the principle of bioisostere and hybrid-ization. They exerted inhibitory activity against adenosine diphosphate ( ADP )-induced and arachidonic acid ( AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC50 of 0. 14 mmol/L on ADP-induced platelet aggregation ( 9. 1 folds of TMP and 10. 5 folds of chalcone ) and 0. 09 mmol/L on AA-induced platelet aggregation ( 8. 8 folds of TMP and 10. 0 folds of chalcone) , which was superior to clinically used anti-platelet drug aspirin ( ASP, IC50 =0. 15 mmol/L) .

Content Determination of Preservative Ethylparaben in Hospital Preparation / 中国药房

OBJECTIVE: To establish a RP-HPLC method for the determination of preservative ethylparaben content in hospital preparation.METHODS: The determination was carried out on Spherisorb C18 column and the mobile phase consisted of acetonitrile-water(50∶50,V/V) at a flow rate of 1 mL?min-1.The column temperature was set at 35 ℃;the detection wavelength was set at 254 nm and the sample size was 20 ?L.RESULTS: The linear range of ethylparaben was 1.812 5～18.125 0 ?g?mL-1(r=0.999 9) with an average recovery rate of 99.92%.The intra-day RSD was less than 2.10% and inter-day RSD was less than 4.89%.CONCLUSION: The method is simple,rapid and accurate,and applicable for the determination of ethylparaben content in hospital preparation.

Formulation,Technology and Quality Evaluation of Dexamethasone Solid Lipid Nanoparticles Lyophilized Injection / 中国药房

OBJECTIVE: To study the formulation and technology of dexamethasone solid lipid nanoparticles(DXM-SLN) lyophilized injection and evalnate it's quality. METHODS: The formulation of the supporting agent was optimized and the preparation technology of lyophilized injection was established to prepare the lyophilised injection. The content of DXM in the sample was determined and its quality was investigated as well. RESULTS: 30% mannitol was supporting agent, the particle size of DXM-SLN was 340 nm, with zeta potential at -25.2 mV, entrapment ratio at 92.10% and drug-loading at 7.10%. It was stable within 3 months' at 2～8 ℃storing. CONCLUSION: The preparation technique of this preparation is simple and feasible and its quality is stable and controllable.

Quality Evaluation of Levofloxacin Tablets Produced by Six Different Pharmaceutical Factories / 中国药房

OBJECTIVE:To evaluate the quality of levofloxacin tablets produced by 6 different factories.METHODS:To investigate the quality of 17 batches of levofloxacin tablets produced by 6 factories according to related standards and to evaluate the drug dissolubilities using paddle method.RESULTS:17 products from six factories were all proved qualified.Significant differences of dissolution parameters and treatment costs were found among the different products.CONCLUSION:There are difference in quality of levofloxacin tablets.The tablets produced by the factory holding the patent right are more expensive,however the qualiity is more stable.