基于临床药师动态监测的药物超常预警临床实践

介绍临床药师在动态监测和超常预警中承担的工作,包括医嘱审核、药物重整、用量分析及异常增长监控、科室指标的解读及实施、持续监测、超常预警的后续跟进与反馈等工作,通过比较2020—2022年我院销售金额排名前20位药品类别变化、重点监控药品用药金额变化、次均药费和例均药费增幅变化,评估临床药师在此管理中发挥的作用。结果显示,2020—2022年我院销售金额排名前20位药品类别组成更加合理;重点监控药品用药金额、门急诊次均药品费用和住院例均药品费用呈现逐年递减趋势,2022年重点监控药品用药金额较2021年降低10.07%;门急诊次均药品费用较2021年下降了7.20%;住院例均药品费用较2021年下降了17.70%。由此可以看出临床药师在药品动态监测和超常预警中发挥了重要作用,有效控制了医院用药成本,促进了临床合理用药。

恩沙替尼、安罗替尼、培美曲塞、唑来膦酸联用致重度贫血1例

1例42岁男性Ⅳ期右肺腺癌患者,病史9年,既往曾予多种化疗和靶向药物,因疾病进展,靶向治疗调整为盐酸恩沙替尼胶囊,联合安罗替尼、培美曲塞二钠和唑来膦酸抗肿瘤治疗。患者连续服用恩沙替尼胶囊82 d后,无明显诱因突发乏力,血红蛋白从用药前的132 g·L^(-1)降至59 g·L^(-1),确诊为重度贫血,考虑与恩沙替尼、安罗替尼、培美曲塞以及唑来膦酸相关,不良反应关联性评价为“可能”。经停药、对症支持治疗后,入院第6天血红蛋白恢复至97 g·L^(-1)。恩沙替尼在我国上市时间较短,出现重度贫血的相关报道较少。该病例提示临床治疗中应重点关注使用经验较为有限的药物,及时发现其少见的不良反应。

Paris chinensis dioscin induces G2/M cell cycle arrest and apoptosis in human gastric cancer SGC-7901 cells

AIM:To investigate the anti-tumor effects of Paris chinensis dioscin(PCD)and mechanisms regarding cell cycle regulation and apoptosis in human gastric cancer SGC-7901 cells.METHODS:Cell viability was analyzed by the 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay.Cell apoptosis was evaluated by flow cytometry and laser scanning confocal microscope(LSCM)using Annexin-V/propidium iodide(PI)staining,and the cell cycle was evaluated using PI staining with flow cytom-etry.Intracellular calcium ions were detected under fluorescence microscope.The expression of cell cycle and apoptosis-related proteins cyclin B1,CDK1,cytochrome C and caspase-3 was measured by immunohistochemical staining.RESULTS:PCD had an anti-proliferation effect on human gastric cancer SGC-7901 cells in a dose-and time-de-pendent manner.After treatment of SGC-7901 cells with PCD,apoptosis appeared in SGC-7901 cells.Morpho-logical changes typical of apoptosis were also observed with LSCM by Annexin V/PI staining,and the cell number of the G0/G1 phase was decreased,while the number of cells in the G2/M phase was increased.Cell cycle-related proteins,such as cyclin B1 and CDK1,were all down-regulated,but caspase-3 and cytochrome C were up-regulated.Moreover,intracellular calcium accumulation occurred in PCD-treated cells.CONCLUSION:G2/M phase arrest and apoptosis induced by PCD are associated with the inhibition of CDK-activating kinase activity and the activation of Ca2+-related mitochondrion pathway in SGC-7901 cells.

Plasmid-based generation of neural cells from human fibroblasts using non-integrating episomal vectors

Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine.

Simultaneous Determination of Five Hydrophilic and Lipophilic Components from roots of Salvia miltiorrhiza by HPLC

Objective A reversed-phase HPLC method was established for the simultaneous determination of five hydrophilic and lipophilic components in the roots of Salvia miltiorrhiza. Methods Hydrophilic components including danshensu, protocatechuic aldehyde, and salvianolic acid B, and lipophilic components such as cryptotanshinone and tanshinone liA, were successfully separated on a Waters Symmetry C18 reverse- phase column （250 mm×4.6 mm, 5 μm）, with acetonitrile-0.5% phosphoric acid （gradient elution） as mobile phase, the detection wavelength was set at 281 nm with flow rate of 1.0 mL/min, and the column temperature was maintained at 30 ~C. Results The recovery of the method was in the range of 95.1%-102.5% and the precision was less than 3% for all five analytes. All the compounds showed good linearity （R2 〉 0.9990） in a relatively wide concentration range. Therefore, this HPLC method demonstrated good reproducibility, stability, and accuracy in validation studies. Conclusion Simultaneous quantification of the multiple components by HPLC would be a better strategy for the quality evaluation on the roots of S. miltiorrhiza.

Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

Background：High-dose methotrexate （HD-MTX） with folinic acid （leucovorin） rescue is ＆quot;gold standard＆quot; therapy for osteosarcoma.Plasma concentrations of methotrexate （MTX） are closely related to its efficacy and toxicity.Delayed excretion of MTX can lead to serious adverse reactions that may result in treatment cessation,irreversible organ damage,and death.This study focused on the incidence of delayed excretion of MTX in Chinese osteosarcoma patients.Methods：A total of 1277 osteosarcoma patients were treated with HD-MTX chemotherapy （4291 cycles） from 2010 to 2015.Factors that could influence delayed excretion of MTX （gender,age,number of chemotherapy cycles,and serum concentration of MTX） were analyzed.Results：The incidence of delayed excretion of MTX （serum concentrations at 24 h [C24 h] 〉5 μmol/L） and severe delayed excretion of MTX （C24 h 〉20 μmol/L） were 6.19% and 0.86% per patient,and 2.31% and 0.26% per cycle of treatment,respectively.The incidence of severe delayed excretion of MTX was associated with gender,age,and C24 h.Conclusions：Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX.An optimal individualized rescue strategy can be created with consideration of gender,age,and C24 h.

Comparison of volatile profiles and bioactive components of sun-dried Pu-erh tea leaves from ancient tea plants on Bulang Mountain measured by GC-MS and HPLC

To explore the volatile profiles and the contents of ten bioactive components(polyphenols and caffeine) of sun-dried Pu-erh tea leaves from ancient tea plants on Bulang Mountain,17 samples of three tea varieties were analyzed by headspace-solid phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS) and high-performance liquid chromatography(HPLC).A total of 75 volatile components were tentatively identified.Laomaner(LME),Laobanzhang(LBZ),and other teas on Bulang Mountain(BL) contained 70,53,and 71 volatile compounds,respectively.Among the volatile compounds,alcohols(30.2%-45.8%),hydrocarbons(13.7%-17.5%),and ketones(12.4%-23.4%) were qualitatively the most dominant volatile compounds in the different tea varieties.The average content of polyphenol was highest in LME(102.1 mg/g),followed by BL(98.7 mg/g) and LBZ(88.0 mg/g),while caffeine showed the opposite trend,27.3 mg/g in LME,33.5 mg/g in BL,and 38.1 mg/g in LBZ.Principal component analysis applied to both the volatile compounds and ten bioactive components showed a poor separation of samples according to varieties,while partial least squares-discriminant analysis(PLS-DA) showed satisfactory discrimination.Thirty-four volatile components and five bioactive compounds were selected as major discriminators(variable importance in projection(VIP)>1) among the tea varieties.These results suggest that chromatographic data combined with multivariate analysis could provide a useful technique to characterize and distinguish the sun-dried Pu-erh tea leaves from ancient tea varieties on Bulang Mountain.