Objective To evaluate the safety of blood concentration monitoring on methotrexate for malignant tumor patients . Methods Randomized controlled trials(RCTs) and observational studies were searched from PubMed,Cochrane Library,EMBase,Ovid Technologies,CNKI,VIP and Wanfang data. According to the inclusion and exclusion criteria,the qualified literatures were selected and the Meta-analysis was performed. The retrieval time was from the of establishment of databases to the October 2016. The patients with malignant tumor treated with methotrexate and performed quality evaluation of blood concentration were included,including 287 patients and 2 tumor types,the Revman 5. 3 software was used to carry out statistics and analysis for the results. Results Three RCTs and one observational studies were included. Compared with the tumor patients who did not do blood concentration monitoring,the adverse reactions included adverse reactions in gastrointestinal tract,oral ulcer,abnormal liver function,limb discomfort,skin and mucosa damage in the blood concentration monitoring group were significantly reduced(P < 0. 05),but the incidence rate of myelosuppression was high. Conclusion Blood concentration monitoring for malignant tumor patients treated with methotrexate can effectively reduce the in-cidence of adverse reactions.

Objective To probe clinical outcome of acute myeloid leukemia which induced by treated with DA (Daunorubicin+Cytarabine) regimen contained with different dose of daunorubicin.Methods Retrospective analysis of 76 patients with acute myeloid leukemia of multiple medical research centre in our province from August 2013 to November 2016,which were divided into A group,B group and C group.Observation on the complete remission (CR) rate and survival rate of three groups after treatment.Results There were 12 patients in group A,54 patients in group B,and 10 patients in group C.After the first induced treatment,effective rate was 83.33%,CR rate was 66.67% in group A,effective rate was 92.60%,CR rate was 83.33% in group B,effective rate was 90.00%,CR rate was 80.00% in group C.73 patients were evaluated in the second course of treatment,effective rate was 83.33%,CR rate was 83.33% in group A,effective rate was 90.74%,CR rate was 88.87% in group B,effective rate was 85.71%,CR rate was 85.71% in group C.51 patients were evaluated after six courses of treatment,6 patients in group A,42 patients in group B,3 patients in group C,OS rate was 100%,92.86% and 100% in group A,group B and group C respectively.1-year total OS rate and PFS was 82.22% and 64.44% respectively after follow-up of 1 year with 45 patients,2-year total OS rate and PFS was 74.36% and 61.54% respectively after follow-up of 2 years.Conclusion It is effective treatment in primary acute myeloid leukemia which induced by treated with reduced-dose DA regimen.It is low toxicity and applicable to the elderly,poor physical condition,complications and poor economic condition patients compared with the higher dose,but it not routinely recommended because disease easy to progress after reduced-dose treated.

Objective To study the effects of Heme oxygenase-1 (HO-1) on the reduction of nitroglycerin tolerance in vitro.Methods Tolerance was induced by exposure of nitroglycerin (GTN)for 10min and then 16 h in human umbilical vein cells (HUVECs).RT-PCR and Western-blot (WB) were used to evaluate HO-1 gene and protein expression after HO-1 gene regulation by hemin and ZnPP.The level of NO and ROS was observed after gene regulation.Results Compared with the control group,the HO-1 gene up-regulation group had a higher cell survival rate against GTN induced damage (P<0.05).The generation of NO was increase in the gene up-regulation group (P<0.01).Meanwhile compared with the control group,the generation of intracellular ROS was downregulated and NO was upregulated in hemin group (P<0.01).Conclusion HO-1 gene up-regulation could improve nitroglycerin tolerance,and the oxidative stress may be involved in the process of these effects.

OBJECTIVE:To study protective effects of glutamine (Gln) on cardiac muscle cell in septic model rats. METH-ODS:Rats were randomly divided into sham operation group (normal saline),model group (normal saline) and Gln low-dose, medium-dose and high-dose groups(0.5,0.75,1.0 g/kg)with 10 rats in each group. In these groups,septic rat model was induced by cecal ligation and puncture except sham operation group received sham operation. They were given relevant medicine intrave-nously 10 min after operation,and the characteristics and apoptosis of cardiac muscle cell were observed 12 h after operation. The serum contents of CK,LDH and TnⅠ,and the expression of Bcl-2 and p53 mRNA were all detected. RESULTS:Compared with sham operation group,myocardial necrosis of model group was found,and the serum content of CK,LDH and TnⅠ and apoptotic index increased,and mRNA expression of Bcl-2 in cardiac muscle cell decreased while that of p53 increased,with statistical signifi-cance(P<0.05). Compared with model group,myocardial injury relieved significantly in Gln high-dose and medium-dose groups, and serum contents of CK,LDH and TnⅠ and apoptotic index decreased;mRNA expression of Bcl-2 increased in cardiac muscle cell while that of p53 decreased,with statistical significance (P<0.05). CONCLUSIONS:Gln can improve myocardial injury of septic model rats significantly,by a possible mechanism of down-regulating the expression of p53 gene and up-regulating the ex-pression of Bcl-2 gene.

1 病例资料 男性患者,48岁,因呼吸困难伴全身皮疹2 h入院.于2 h前肌注双氯芬酸钠盐酸利多卡因注射液后出现呼吸困难伴全身皮肤瘙痒、皮疹,有胸闷、头昏、黑矇,无咳嗽、咳痰、胸痛、晕厥,急诊测血压(舒张压/收缩压)为70/40 mmHg ( 1 mmHg=0.133 kPa),指脉血氧饱和度75%,并呈进行性下降,考虑过敏性休克,立即给予静脉滴注地塞米松10 mg,氢化可的松100 mg,肌肉注射异丙嗪25 mg,20 min后,患者血氧饱和度上升至90%以上,血压波动于110/70 mmHg左右,为进一步治疗,于2014年12月26日收入重症监护室.患者既往史:平素体健,40年前于当地医院诊断为先天性心脏病(具体不详),己行手术治愈,术后患者无劳累性胸闷、气促等症状.6年前诊断为泌尿系结石,予以输液治疗(具体不详),近日有肾绞痛,给予肌注双氯芬酸钠盐酸利多卡因注射液止痛治疗;否认"冠心病、肾病、高血压病"等慢性病史,否认"结核、肝炎、伤寒"等传染病史.对青霉素过敏,无食物过敏史.

Objective:To investigate the betulinic acid combined with Thalidomide induce apoptosis of U266 cells and its mechanism. Methods:U266 cells were treated with betulinic acid(20,40,60 and 80 mg/L,betulinic acid group ),Thalidomide( 10 mg/L,50 mg/L,100 mg/L,Thalidomide group)and betulinic acid(40 mg/L)combined with Thalidomide( betulinic acid 40 mg/L,10,50 and 100 mg/L of Thalidomide,combined group)coupled with control group. Proliferation inhibition rate and apoptosis rate of U266 cells from different concentrations were detected with MTT and flow cy-tometry;Real-time PCR was used to detect the expression levels of Survivin,Cyto-C,Bcl-2,Bax gene. Western blotting was used to detect the expression of Survivin,Cyto-C,Bcl-2,Bax protein. Re-sults:With the increase of betulinic acid concentration,inhibition rate of U266 cells was also in-creased,differences were statistically significant( P <0. 05),the most appropriate concentration was 40 mg/L ;comparing with Thalidomide,inhibition rate and apoptosis rate of U266 cells were obviously increased,differences were statistically significant(P<0. 05);comparing with Thalidomide group or betulinic acid group,Survivin and expression of Bcl-2 mRNA of U2666 cells obviously decreased,Cy-to-C and expression of Bax mRNA obviously increased,differences were statistically significant(P<0. 05 ). Conclusion:The betulinic acid combined with thalidomide induce apoptosis of multiple myeloma U266 cells and its mechanism may be correlated with the proapoptotic molecule of survivin,Bcl-2,Cy-to-c and Bax.

目的:对紫杉醇聚乙二醇单甲醚-乳酸-羟基醋酸嵌段共聚物进行大鼠体内药动学考察.方法:SD大鼠以6mg·kg-1剂量于尾静脉注射自制紫杉醇聚乙二醇单甲醚-乳酸-羟基醋酸嵌段共聚物与紫杉醇注射液,以高效液相色谱仪测定给药后不同时间血浆中紫杉醇的药物浓度.结果:紫杉醇聚乙二醇单甲醚-乳酸-羟基醋酸嵌段共聚物与紫杉醇注射液经大鼠尾静脉注射后均符合二室模型,t1/2α分别为(12.45±3.06) min和(2.37±1.71)min; t1/2β分别为(43.27±14.55)min和(38.50±2.26)min; AUC分别为(2 381.22±314.31)mg·L-1·min和(1 156.33±300.04)mg·L-1·min.结论:紫杉醇与聚乙二醇单甲醚-乳酸-羟基醋酸形成嵌段共聚物后,紫杉醇体内消除减慢,驻留时间延长,维持较高药物浓度时间延长.

目的：促进临床中药注射液使用安全性的提高。方法：根据药物机体免疫损伤机制，对清开灵注射液处方成分进行过敏反应风险评估。结果：清开灵注射液处方中有含外源性蛋白质的3味植物和2位动物药材，其中水牛角（粉）外源性蛋白含量最高，触发过敏反应的风险最大；与CFDA公布的2013年中药注射剂严重不良反应/事件报告前九位处方相比较，其处方组成最复杂，且唯一含动物类药材的处方，这或许是该注射剂严重不良反应/事件报告占据首位的原因之一。结论：重视对生产企业和处方医生的监管，以保证患者药品使用安全的基本权利。

Objective:To investigate the preventative application of antibacterials during perioperative period in our hospital. Methods:A retrospective investigation was conducted to analyze the clinical data of the inpatients from Jul. to Dec. of 2011 in our hospital and to evaluate the rationality of the use of antibacterials during perioperation. Results:The rate of irrational use of antibacterials during perioperation was 56.73%. Cephalosporins were used with the highest frequency. The rate of single agent use was 92.30% and that of combined use of two antibacterials was 7.70%. There was no case of combined use of three or more than three antibacterials. The irrational drug use was mainly manifested in the postoperative long medication, improper timing of administration, high grade drug selection and inappropriate usage or dosage, etc. Conclusion:Irrational use of antibacterials during perioperation existed in our hospital, therefore measures need to be taken by the hospital to improve the training on the correct use of antibacterials and to strengthen the management on the preventative application of antibacterials during perioperative period.

OBJECTIVE:To study the role of clinical pharmacists in the treatment for patients with allogeneic peripheral blood stem cell transplantation(allo-PBSCT).METHODS:Clinical pharmacists provided pharmaceutical care for 2 cases of allo-PBSCT,participated in the formulation of therapeutic plan,ward-round and case discussion,and carried out pharmaceutical care and medication education.RESULTS:11 days after allo-PBSCT,routine blood test of patient A reminded hematopoietic reconstruction;HCMV-DNA was negative;bone marrow inspection showed active bone marrow hyperplasia;the vital signs of patients were stable without fever and other ADR.11 days after allo-PBSCT,routine blood test of patient B reminded hematopoietic reconstruction;HCMV-DNA was negative;bone marrow inspection showed myeloid cell hyperplasia and low erythroid cell hyperplasia;no fever,erythra and other GVHD manifestation were found.CONCLUSION:Through clinical pharmacists participate in pharmaceutical care for allo-PBSCT patients,and collaborate with doctors on medical plan to improve the acceptance of doctors,nurses and patients for clinical pharmacists and realize the value of them.

目的 研究逆转录病毒介导的血红素加氧酶-1(HO-1)基因在尼洛替尼(Nilotinib,AMN107)诱导慢性髓性白血病(CML)耐药细胞凋亡中的作用.方法 制备高病毒滴度的逆转录病毒载体pQCXIP-EGFP-HO-1,建立稳定转染HO-1基因的K562/A02细胞.采用RT-PCR鉴定K562/A02细胞中HO-1基因的表达.RT-PCR和Western blot法检测AMNl07作用24 h后K562/A02细胞中HO-1 mRNA和蛋白的表达,采用MTT法观察细胞增殖变化,通过实时荧光定量PCR(RQ-PCR)法检测bcr-abl融合基凶的表达.通过流式细胞术检测细胞凋亡和细胞周期分布.结果 成功构建重组逆转录病毒载体,并建立稳定转染HO-1基因的K562/A02细胞系;证实转基冈组细胞HO-1 mRNA显著表达.AMN107作用3组细胞后,转基因组细胞HO-1 mRNA和蛋白的表达明显高于转空载体组和未转染组,差异有统计学意义(P<0.05);MTT法检测显示AMN107处理后细胞增殖受抑.而转基因组细胞存活率明显高于转空载体组和未转染组,差异有统计学意义(P<0.05);RQ-PCR法检测结果显示,10 ILLmol/L AMNl07抑制bcr-abl基因的表达,但转基因组的bcr-abl基因表达水平(Ct值18.15±0.18)高于转空载体组(20.32±0.20)和未转染组(20.51±0.21),差异有统计学意义(P<0.05);流式细胞术检测结果显示10 μmol/L AMNl07作用24 h后,转基因组、转空载体组、未转染组细胞凋亡率分别为(17.26±0.23)%、(39.47±0.17)%、(41.84±0.09)%.未加药转基因组、未加药未转染组细胞凋亡率分别为(3.74±0.03)%、(5.91±0.08)%;细胞周期分析结果显示经AMNl07处理后,Go/G1期和S期细胞明显减少,细胞阻滞在G2/M期,而转基因细胞组细胞周期改变不如转空载体组、未转染组明显.结论 AMN107可抑制CML耐药细胞增殖且诱导细胞凋亡,HO-1基因在CML耐药细胞凋亡过程中起保护作用,与促进CML耐药细胞的生长有关.

Objective To establish the rat model of morphine-induced conditioned place preference(CPP),and to investigate the roles of brain-droved neurotrophic factor(BDNF)and c-fos in morphine psychological dependence. Methods Morphine was administrated via subcutaneous injection at mg/kg·d-1 for 6 days to induce morphine-induced conditioned place preference.The expression of BDNF and c-fos in the cortex were estimated by immunohistochemistry. Results The time spent in morphine-paired side was significantly increased in morphine-group trained after morphine treatment for 6 days,Compared with control group,P<0.01.The mean optical density and positive cell of the BDNF and c-fos in cortex significantly increased in morphine group(P<0.01,P<0.01). Conclusion Morphine can induce the CPP in rats.The expression of BDNF and c-fos can increase in rat cortex after chronic morphine treatment,which suggests that BDNF and c-fos may be related to the development of morphine dependence.

OBJECTIVE To evaluate the drug interaction and the rationality of combined drug treatment,the pharmacokinetics of 17-AAG with combinated imatinib in rats were studied.METHODS There are two dosage regimens to administrate in rats separately as follow:imatinib administered at a dose of 40 mg·kg-1;imatinib 40 mg·kg-1 and 17-AAG 15 mg·kg-1;the concentrations of imatinib in rats were determined after intr-agastric(ig) administration.The plasma concentration of the imatinib was measured by reversed phase HPLC,the compartment model was calculated by 3p87 software and the pharmacokinetic parameters were compared with SPSS software.RESULTS Imatinib could be fitted to one compartment model in rats.After intra-gastric administration of imatinib alone or the combination of imatinib with 17-AGG,the main pharmacokinetic parameters t1/2,Cmax,tmax,AUC had significant difference respectively by analysis of test(P<0.05).CONCLUSION The pharmacokinetic characters was changed after combined-use of imatinib and 17-AGG,they interacted with each other in pharmacokinetics.There is a drug interaction on each other in rats.

紫杉醇(Paclitaxel,Taxol)是从红豆杉属植物紫杉的树干和树皮中提取的一种天然抗癌药物,临床研究已经证实了紫杉醇在抗多种实体肿瘤,包括乳癌、晚期卵巢癌、肺癌、脑部和颈部肿瘤以及急性白血病等方面都有重要而显著的作用[1].

目的:分析探讨药源性医疗事故争议的性质、特点、原因,提出积极有效地预防措施和建议。方法:以贵州省医学会纂写的《医疗事故鉴定案例百例汇编》作为资料来源,重点回顾性统计、分析2002年9月—2004年3月,贵州省和有关地州市医学会医疗事故技术鉴定工作办公室已鉴定的100例医疗事故争议中,19例由药物引起的医疗事故争议。结果:经鉴定构成医疗事故的为66例,不构成事故的为34例,其中构成药源性医疗事故的为13例,药源性医疗事故占医疗事故总数的19.69%。其中一级9例,占事故总数的13.63%;二级0例;三级1例,占事故总数的1.52%;四级3例,占事故总数的4.54%。结论:药物不良反应、遴选药品、药物剂量、给药途径、误用药物、药物配伍禁忌等因素均会造成药源性医疗事故的发生,临床医务人员应加强培训,提高业务水平,掌握药物知识,合理使用药物,提高职业道德素质,健全、完善医院各种规章制度,以减少或避免药源性医疗事故的发生。

紫杉醇(paclitaxel)是近20年来发现的疗效显著的抗癌药物之一.与其他抗癌药物不同,紫杉醇是通过诱导和促进微管蛋白聚合、装配及稳定微管作用阻止肿瘤细胞生长[1],对卵巢癌、乳腺癌、头颈部癌、非小细胞性肺癌及前列腺癌疗效显著[2-4],目前临床上使用紫杉醇注射剂多用静脉给药,但市售紫杉醇注射液中使用了较大量的增溶剂cremophorEL,其在体内可引起较严重的急性过敏反应,给患者带来不便和痛苦.我院建立一种以叔丁基甲醚为提取剂的高效液相色谱法测定大鼠血中紫杉醇的浓度,方法准确、灵敏、简单、快速,为后续研究奠定了基础.

OBJECTIVE: To investigate clinical efficacy and toxic reaction of idarubicin (IDA), daunorubicin (DNR), mitoxantrone (MTN) and theprubicine (THP) in the treatment of acute myeloid leukemia. METHODS: 62 patients with acute myeloid leukemia were selected from our hospital during the period of Apr. 2005～Apr. 2010 and randomly divided into 2 groups. Treatment group received IDA and Ara-C (n=30) and control group DNR, MTN or THP combined with Ara-C (n=32). RESULTS: The complete remission (CR) rates were 80.0% for treatment group and 43.8% for control group. The total effective rates (RR) of treatment group and control group were 93.3% and 68.8%, respectively. The rates of severe infection in the clinic were 36.7% and 34.4%, respectively. There were statistical significances in the difference of CR rate and RR rate between 2 groups (P0.05), while there was no statistical significance in the differences of rate of severe infection between 2 groups (P0.05). CONCLUSION: Combined chemotherapeutic scheme containing IDA have sound effect on the acute myeloid leukemia.

Aim:To observe the expression of brain-drived neurophic factor(BDNF) and c-fos in hippocampus of rats with morphine conditioned place preference(CPP) after environment induced reinstatement and to evaluate the influence of BDNF and c-fos on addiction memory.Methods:A total of 36 rat were randomly allocated into 3 groups(normal saline control group,extinction group,and reinstatement group,12 in each group).Rats in extinction group and reinstatement group were to establish the CPP model of morphine.Reinstatement group was induced by environment after extinction of CPP.The residence time in white box within 15 min was recorded,and the expression of BDNF and c-fos in hippocampus of rats were estimated by immunohistochemistry.Results:There were significant differences in the residence time among the 3 groups at different time point(Ftime=5.76,P=0.007;Fgroup=4.07,P=0.028).The mean optical density and the number of positive cells of BDNF and c-fos in hippocampus significantly increased in reinstatement group compared with those of saline control group and extinction group(P0.01).Conclusion:BDNF and c-fos may be related to the addiction memory and participate in the environment induced reinstatement to morphine CPP.