Objective To investigate the effect of venetoclax on RNA expression and cytokines release in lymphocytes isolated from acute myeloid leukemia(AML) patients. Methods MTT method was performed to study the apoptosis of AML cells and optimize the concentration of venetoclax.The gene markers expression and cytokines production before and after venetoclax treatment were examined by RT-PCR and ELISA methods,respectively. Results After chemotherapy,the expression of tumor associated inhibitory genes including BCL-2(P<0.05),SIRPα(P<0.05),CD47(P<0.05),PDL-1(P<0.05),PDL-2 (P<0.01),and EZH2(P<0.05) were significantly decreased when venetoclax reached 300 nmol·L-1.In addition,the expression levels of the activated molecules significantly increased,such as TRAIL(P<0.01) and TNF-α(P<0.01).The ELISA results showed that the release of human TNF-α and IFN-γ have significantly increased. Conclusion Venetoclax,which is a chemotherapeutic drug,can be used as tumor targeting drug.It can promote apoptosis in AML patients by regulating the genes expressions related to malignancy and cytokines production.
Objective:Through the clinical practice of beside pharmacists,to summarize the problems of drug administration for the patients,explore the significance of pharmacists in guiding the clinical drug use and the establishment of medical care mutual cooperation mode to suit the actual situation of our hospital to provide a better service for patients.Methods:Through intervention and guidance of 1,440 cases of children in department of respiration with drug use,the problems and results of clinical interventions were analyzed by bedside pharmacists.Results:There were 540 cases (37.50%) of wrong timing of administration,274 cases (19.03%) of usage errors,67 cases (4.65%) of improper drug storage,20 cases (1.39%) of missing medication and 12 cases (0.83%) of repeated medication.Conclusion:The guidance on patients' medication of bedside pharmacists in the clinical departments can improve patients'compliance,intervene irrational use of drugs,give full play to the professional role of pharmacists to ensure the safety of patients with medication,so as to achieve better therapeutic effect.
Sebelipase alfa is a drug for the treatment of a rare disease - lysosome acid lipase deifciency (LAL-d) caused by mutations of chronic progressive metabolic diseases. LAL-d can lead to growth disorders, abnormal accumulation of liver lipid, liver ifbrosis and cirrhosis of the liver and so on. Sebelipase alfa is the ifrst symptomatic biological agents for the treatment of lysosome acid lipase deifciency granted by FDA as a orphan drug.
Objective To investigate the current situation of off-label drug use in hospitalized children in Pediatric Digestive Department.Methods Clinical records of 300 children were randomly collected from 1 560 cases of gastrointestinal diseases in Pediatric Digestive Department of the First Hospital of Jilin University from July 1,2015 to June 30,2016;totally 11 400 medical orders involving 201 kinds of drugs were reviewed.Use of medicines in children was analyzed according to Notes on Clinical Medication of Chinese Pharmacopoeia,New Pharmacology,National Formulary,Prescription Management and drug instructions;medical orders that were inconsistent with the regulations were defined as off-label drug use.Results Incidence rate of off-label drug use was 84.7% (254/300);off-label rate of medical orders was 26.3% (2 998/11 400).Main causes of off-label drug use included lack of notes for children [75.2% (2 277/3 025)],over-indication [7.1% (216/3 025)],off-label dosage[6.4% (194/3 025)] and off-label frequency of administration [5.6% (170/3 025)].Off-label medication mainly involved antibacterial,antiviral,digestive and respiratory drugs.Conclusion Off-label drug use is common in Pediatric Digestive Department that needs urgent management of medical regulations.
1 病例资料 患儿,男,14岁. 因"入院前4 d无明显诱因出现腰痛,入院前3 d加重",于2015年12月25日就诊于吉林大学第一医院小儿肾病科. 患儿于2015年12月19日无明显诱因发热,体温最高37.8 ℃,伴有咽痛.患儿于一天内分两次口服复方氨酚烷胺胶囊(江西铜鼓仁和制药有限公司,规格:每粒含对乙酰氨基酚250 mg、盐酸金刚烷胺100 mg、马来酸氯苯那敏2 mg、人工牛黄10 mg、咖啡因15 mg ) ,每次6粒,服药后未再发热,咽痛好转,服药48 h内无明显诱因出现腰痛,入院前3d加重,入院前2d就诊于当地医院,实验室检查发现蛋白尿(+++)、血肌酐(Cr)165.4 μmolL-1,为求进一步诊治就诊于吉林大学第一医院. 入院体格检查: 体 温 36.2 ℃, 脉 搏 80 次min-1 , 呼 吸18次min-1 , 血 压: 113/64 mmHg ( 1 mmHg =0.133 kPa) ,体质量50 kg. 咽部充血,肾区叩痛阳性,其他体检未见异常. 入院检查示患儿尿潜血(+),尿蛋白(++) ,尿素氮( BUN ) 10. 12 mmolL-1 , Cr 255.3 μmolL-1 ,eGFR 26. 6 mLmin-1 ,二氧化碳结合力18 mmolL-1. 诊断:急性肾损伤Ⅲ级.
患者,女,64岁。因“突发剧烈头痛,伴恶心、呕吐3 h,于2014年9月30日入院。CT 检查提示“蛛网膜下腔出血”,诊断:动脉瘤破裂出血。10月4日预行支架辅助动脉瘤栓塞术,10月3日口服阿司匹林肠溶片(Bayer HealthCare Manufacturing S.r.l.,批号:BJ19388)300 mg qd,硫酸氢氯吡格雷片(杭州赛诺菲安万特民生制药,批号:4A678)300 mg qd,从10月5日开始服用阿司匹林肠溶片100 mg qd,联合硫酸氢氯吡格雷片75 mg qd。10月19日查体见患者面色较前苍白,红细胞2.83×1012·L-1,血红蛋白84g·L-1。10月20日红细胞1.83×1012·L-1,血红蛋白54g·L-1,尿素氮7.20mmol·L-1。10月21日突发血压降低,心率加快,红细胞1.61×1012·L-1,血红蛋白47g·L-1,灌肠后排出大量黑色脓血便。胃镜提示:慢性胃炎伴糜烂、胃多发溃疡(A1期),十二指肠球部溃疡(A2期)。给予止血、抑酸、补液、输血、对症、支持治疗,10月22日停服阿司匹林肠溶片和硫酸氢氯吡格雷片。10月23日红细胞2.96×1012·L-1,血红蛋白90 g·L-1,同时患者无呕血及排黑便,考虑出血停止。医师预单药选用氯吡格雷抗血小板治疗,临床药师建议,单药选用阿司匹林肠溶片抗血小板治疗更合理,将奥美拉唑更换为泮托拉唑,同时服用胃黏膜保护剂4~8周,医师采纳。从10月23日开始,该患者口服阿司匹林肠溶片100 mg qd,泮托拉唑肠溶片40 mg bid.,磷酸铝凝胶2.5 g tid.,病情平稳,于10月29日出院,嘱其提高用药依从性,定期复查胃镜和血小板聚集功能。
钠离子牛磺胆酸共转运多肽( Na+-taurocholate cotransporting polypeptide,NTCP)是乙型肝炎病毒( hepatitis B virus,HBV)感染的受体,此发现为抗HBV新药研发提供了新靶标。本文综合了近3年来对NTCP受体的研究,全面阐述了目前HBV治疗中的瓶颈、NTCP发现的意义及其表达调节,以及进入抑制剂的种类、作用机制和研究进展。进入抑制剂将成为抗HBV感染的新靶点,并有可能成为抗HBV感染的新的策略之一。
Objective:To study the bioactivity of thymosin β16 (Tβ16) in vitro and in vivo.Methods:Recombinant His-SUMO-Tβ16 was constructed and transformed into E.coli BL21(DE3) for induced expression.The product was treated by ultrasonication,ion-exchange chromatography and metal chelation chromatography respectively for purification.The fusion protein was cut by His-SUMO protease and then further purified by metal chelation chromatography and Superdex 30 gel chromatography.Results:Recombinant fusion protein His-SUMO-Tβ16 was soluble,whose specific activity was 5.3×105 U/mg.It could promote the proliferation of BALB/c 3T3 cells,rabbit corneal cells,and chicken embryo chorion vessels in vitro,and both the proliferation and migration of vascular endothelial cells in vitro were enhanced,and rabbit skin healing of alkali burns in vivo was accelerated.Conclusion:E.coli expressing vector of recombinant His-SUMO-Tβ16 fusion protein is constructed successfully,and recombinant protein Tβ16 has significant repairing effects.The study established a good foundation for further industrialization of Tβ16.
目的 观察替比夫定治疗慢性乙型肝炎的疗效.方法 给予60例慢性乙型肝炎患者应用替比夫定进行抗病毒治疗,观察治疗结果.结果 替比夫定可使HBV DNA载量下降,丙氨酸转移酶(ALT)降低.结论 替比夫定可明显抑制乙型肝炎病毒复制.
Objectives: To screen small peptides that could antagonize the PGE2 receptor in rheumatoid arthritis (RA) by phage display technology, so that a new way could be found for the treatment of RA. Methods: The T7 select phage was screened and positive clones were selected through the circulation of absorption-ablution-amplification by phage display technology with PGE2 as the targeting selective molecule. After five circulations, phage clones were randomly selected for affinity assessment and the clones with high affinity were picked out for sequencing analysis. Following the synthesizing of T7 peptide, the animal model of adjuvant arthritis was set up to evaluate the anti-inflammatory role of the small synthesized peptides through observing the edema level of paws and detecting proinflammatory cytokine contents by ELISA in synovial exudant. Results: After phage enrichment, 21 positive clones were picked out as positive clones amongst the 23 randomly selected clones. Within the 8 sequenced clones, 4 clones had the identical sequence and the rest clones also had conservative amino residuals. The synthesized T7 peptides could relieve paw edema and decrease the content of proinflammatory cytokines in joint exudant in RA animal model. Conclusions The method of screening the antagonists of PGE2 receptor by phage display is feasible and the T7 peptides have the anti-inflammatory effect.
Objective:To explore the mechanism of activated macrophages contact dependent cytotoxicity.Methods:Activated murine peritoneal macrophages were obtained by introperitoneal injection Bacille Calmette Guerin and fixed with 1% paraformaldehyde. Using these fixed activated macrophages as effector cells, an in vitro cytotoxicity assay was conducted with MCA207 as target cells. The expression levels of Mac-1 and TNF-α on macrophages were examined FITC-conjugated Abs using flow cytometric analysis.Results:MCA207 were killed by macrophages in a cell-contact dependent manner through apoptosis. The apoptosis inducing activity was trypsin sensitive and TNF-α independent.Conclusion:There are some novel protein ligands on the membrane of activated macrophages, which can induce tumor cells apoptosis.
Macrophages are involved in many important biological processes and membrane proteins are the key effector molecules for their functions. However, membrane proteins are difficult to analyze by 2-DE based method because of their intrinsic tendency to self-aggregate during the first dimension separation (IEF). To circumvent the obstacle hampering membrane protein analysis, we combined one-dimensional SDS-PAGE with capillary liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using this technique, we identified 458 GO annotated membrane proteins with extremely high confidence, including most known markers of peritoneal macrophages (e.g., CD11b, F4/80, CD14, CD18, CD86, CD44, CD16 and Toll-like receptor). Thirteen other CD antigens and 18 Ras-related small GTPase were also identified. In addition to those known macrophage membrane proteins, a significant number of novel proteins have also been identified. This research provides a valuable data set of macrophage membrane proteins, thus allowing for more comprehensive study of membrane proteins and a better understanding of the function mechanisms of macrophages in many biological processes.
Macrophages are involved in many important biological processes and membrane proteins are the key effector molecules for their function. However, membrane proteins are difficult to analyze by 2-DE based methods because of their intrinsic tendency to self-aggregate during the first dimension separation (IEF). To circumvent this, we combined one-dimensional SDS-PAGE with capillary liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using this technique, we identified 458 GO annotated membrane proteins with extremely high confidence, including most known markers of peritoneal macrophages (e.g., CD11b, F4/80, CD14, CD18, CD86, CD44, CD16 and Toll-like receptor). Thirteen other CD antigens (CD243, CD98, CD107a, CD107b, CD36, CD97, CD205, CD206, CD180, CD191, CD300, CD45and CD29), and 18 Ras-related small GTPases were also identified. In addition to those known macrophage membrane proteins, a significant number of novel proteins have also been identified. This research not only provides a technique to study membrane proteins, but also a valuable dataset of macrophage antigens, thus providing better understanding of the functional mechanisms of macrophages in many biological processes.
目的: 探讨我院芪杖口服液的制备方法和毒性.方法: 按处方比例经水煎醇沉法制备成口服液,用动物实验观察其毒性.结果: 经急性毒性及长期毒性研究未发现任何毒性反应.结论: 本品制备工艺简单,疗效确切,毒副作用小,值得临床推广应用.
目的:考察20%甘露醇注射液细菌内毒素检查法的可行性.方法:抑制增加试验和对比试验.结果:20%甘露醇注射液样品溶液对鲎试剂无干扰作用,以标示灵敏度为0.5%EU/ml的鲎试剂可用于样品的细菌内毒素检测,与家兔热原检查结果一致.结论:20%甘露醇注射液可用灵敏度为0.5 EU/ml的鲎试剂作细菌毒素检查.
以往,仅用超声检查鉴别诊断乳腺占位性病变的良恶性十分困难.随着具有高频探头的超声诊断仪的问世,尤其以二维图像为基础的多普勒超声(Imagedirected Doppler Ultrasoud,IDU)及彩色多普勒血流显像(Color Dopple Flowing Imaging,CDFI)应用于临床检查后,明显提高了超声诊断乳腺肿块性质的准确率.我们采用IDU和CDFI两种方法对两组病人分别检测乳腺病灶内的血流分布情况,并对二者在鉴别诊断乳腺肿块良、恶性方面的作用进行讨论.