目的 评价替雷利珠单抗单药二线治疗晚期或转移性食管鳞状细胞癌(ESCC)的经济性,为临床合理用药提供参考.方法 从我国卫生体系角度出发,基于RATIONALE-302研究数据构建三状态分区生存模型,模拟时限为10年,循环周期为1个月.采用成本-效用分析法,以质量调整生命年(QALY)作为效用指标并计算增量成本-效果比(ICER),比较替雷利珠单抗单药方案相对于化疗方案二线治疗晚期或转移性ESCC的经济性.采用敏感性分析和情境分析来验证基础分析结果的稳健性.结果 基础分析结果显示,相对于化疗组,替雷利珠单抗组患者的人均增量成本为35025.32元,人均增量效果为2.71 QALYs,ICER为12892.31元/QALY,远低于以3倍2021年我国人均国内生产总值(GDP)即242928元作为的意愿支付(WTP)阈值.单因素敏感性分析结果显示,阿帕替尼成本、疾病进展状态效用值和化疗组不良反应处理成本等参数对ICER值的影响较大,但这些参数均不能导致基础分析结果翻转.概率敏感性分析结果显示,当WTP阈值大于80000元/QALY时,替雷利珠单抗单药方案具有经济性的概率为100％.情境分析结果显示,当模型模拟时限分别为5年和20年时,替雷利珠单抗单药方案的ICER值分别为8331.00元/QALY和12981.00元/QALY,均未超过以3倍2021年我国人均GDP作为的WTP阈值.结论 当以3倍2021年我国人均GDP作为WTP阈值时,相较于化疗方案,替雷利珠单抗单药方案二线治疗晚期或转移性ESCC更具有经济性.

目的 探讨白芷抗惊厥作用的潜在有效成分及作用机制.方法 利用TCMSP数据库筛选白芷有效成分,并收集其对应作用靶点.通过疾病基因综合数据库(GeneCards、OMIM、TTD)检索与convulsion相关靶点;使用R×643.7.2软件绘制韦恩图,筛选白芷有效成分与convulsion交集靶点.采用Cytoscape 3.7.2软件构建"药物-成分-疾病-靶点"网络;使用STRING数据库进行蛋白质相互作用(PPI)网络构建与分析,通过Bioconductor数据库进行KEGG功能富集分析.结果 筛选出白芷有效成分19个,有效成分与疾病convulsion交集靶点24个."药物-成分-疾病-靶点"网络中,β-谷甾醇、豆甾醇、别欧前胡素、珊瑚菜素、欧前胡素和异珊瑚菜素等为该网络主要有效成分.PPI网络中ADRA1B、CASP3、CHRM1、ADRB2、AR和CHRM2等为该网络中核心靶点.KEGG富集分析表明白芷可能通过Neuroactive ligand-receptor interac-tion、Cocaine addiction和Cholinergic synapse等信号通路发挥抗惊厥作用.结论 白芷抗惊厥潜在有效成分主要包括β-谷甾醇、豆甾醇、别欧前胡素、珊瑚菜素、欧前胡素、异珊瑚菜素等,其作用机制可能与参与调控Neuroactive ligand-receptor interaction、Cocaine addiction和Cholinergic synaps等信号通路相关,具有多成分、多靶点、多系统的特点.

The underlying mechanism of the myocardial protective effect of fisetin was studied in a rat ischemia/reperfusion injury model. Sprague-Dawley rats were randomly assigned to seven groups and pretreated with different solutions by gavage administration. A rat model of cardiac ischemia/reperfusion injury was established. Plasma levels of Von Willebrand factor (vWF) were determined by ELISA, flow cytometry was used to determine the level of cardiomyocyte apoptosis and 2,3,5-triphenyltetrazolium staining was used to determine the size of myocardial infarcts. Hematoxylin and eosin-stained sections of myocardial tissues were examined for pathological changes. Expressions of nuclear factor (NF)-κB and matrix metallopeptidase 9 (MMP-9) were measured by immunohistochemistry. Compared with the model group, rats pretreated with fisetin, quercetin and aspirin showed significant prolongation of clotting time, prothrombin time, thrombin time and activated partial thromboplastin time. Fisetin treatment better maintained the integrity of myocardial fibers and nuclear integrity, reduced the percentage of apoptotic myocardial cells, inhibited expression of NF-κB, decreased the loss of MMP-9 and reduced nuclear translocation of NF-kB. Rats pretreated with fisetin also demonstrated a significant decrease in plasma levels of vWF. In addition, the protective effect of fisetin on myocardial cells was found to be dose dependent.

目的:研究红花-甘草配伍对寒凝血瘀模型大鼠血浆及脑组织中三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)及能荷(EC)水平的影响,从能量代谢角度探讨该配伍对寒凝血瘀证的影响.方法:采用冷水冰浴方法成功建立寒凝血瘀证SD大鼠模型,将造模成功大鼠随机分为4组,即模型对照组、红花组、甘草组、红花-甘草组,另设正常对照组.造模成功后,给药组灌胃相应的药物,剂量为20 g·kg-1,模型对照组和正常对照组给予等容积的纯净水,各组均连续灌胃15 d,检测大鼠血浆及脑组织中3种腺苷酸的含量并计算能荷值.结果:与正常对照组相比,模型对照组ATP、ADP的含量及EC值均显著降低(P＜0.01),AMP的含量降低不明显.与模型对照组相比,各给药组ATP、ADP的含量及EC值均显著升高,红花-甘草组改善上述指标的作用强于单药组,差异有显著性(P＜0.05).结论:红花和甘草均可改善寒凝血瘀模型大鼠的能量代谢,促进机体对能量物质的利用,红花-甘草配伍对改善寒凝血瘀证能量代谢显示出更佳的疗效.

Objective To investigate the cost-effect of Vancomycin and Linezolid in the treatment of MRSA infection, providing practical basis for clinical drug use. Methods Patients admitted into our hospital duringfrom January 2014 to March 2016 were retrospectively analyzed. All cases of MRSA infection using Vancomycin or (and) Linezolid as antibiotic therapy were included in this study. The efficacy and pharmacogenomics of Linezolid and Vancomycin in treatment of MRSA were recorded. Results Incidence of renal function in linezolid Linezolid group was significantly lower than that in Vancomycin group (P < 0.05). Time duration of antibiotics usage in Vancomycin group were prolonged compared with linezolid Linezolid group [(7.04 ± 0.45) d vs (5.12 ± 0.47), P < 0.05]. Longer hospitalization stay was also identified in Vancomycin group compared with Linezolid group [(10.76 ± 0.53) d vs (8.06 ± 0.58) d, P < 0.05]. DUI of Vancomycin and Linezolid were both less than 1, while therapeutic effectiveness and cost-effectiveness ratio (C/E) of Linezolid was significantly higher than that in Vancomycin group (P < 0.05).Conclusion Linezolid may be a better choice for treatment of MRSA due to better cost-effectiveness, efficacy and safety compared with Vancomycin.

目的 调查分析我院肿瘤科癌症患者化疗辅助药的使用情况,为促进临床合理用药提供依据.方法 采用回顾性分析法,统计并分析2016年化疗辅助用药的用药频度(DDDs)、药物利用指数(DUI)、销售金额及销售数量等情况.结果 用药金额占比分别为生物免疫调节剂46.09％、扶正祛邪中成药38.00％、保肝药8.45％、抑酸药3.19％、止吐药2.46％、升白细胞药1.81％.DDDs居前5位的是注射用核糖核酸Ⅱ、注射用奥美拉唑钠、参麦注射液、艾迪注射液、注射用还原性谷胱甘肽.排序前15位化疗辅助用药中DUI≤1的药物占66.67％,DUI>1的占33.33％,表明有一些药物使用不当,提示临床医务人员必须加强用药的合理性.结论 化疗辅助用药可以提高机体免疫力,降低抗肿瘤药物的毒性,但用药情况不够规范,滥用辅助用药的情况值得重视.

Objective:To investigate whether the combination of Carthami Flos-Glycyrrhizae Radix et Rhizoma could improve energy metabolism in the tissue of rats with blood stasis syndrome,Carthami Flos-Glycyrrhizae Radix et Rhizoma on adenosine phosphate metabolism of tissues including heart,liver,spleen,lung and kidney were observed.Methods:The SD rats were randomly divided into 4 groups,namely blank control group,model group,Carthami Flos group and Carthami Flos-Glycyrrhizae Radix et Rhizoma group.The blood stasis model rats were made with cold stimulation in cold water ice bath.The blank control group and model group were given saline.The Carthami Flos group and Carthami Flos-Glycyrrhizae Radix et Rhizoma group were given aqueous extract of Carthami Flos and aqueous extract of Carthami Flos-Glycyrrhizae Radix et Rhizoma respectively by intragastric administration once per day according to experimental design for 15 days.At the end of the drug administration for 12 h,the blood and tissues (heart,liver,spleen,lung and kidney) were obtained and hemorheology parameters of rats were measured.The contents of adenosine triphosphate (ATP),adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were determined by using high performance liquid chromatography (HPLC) method.Results:The whole blood viscosity and plasma viscosity were reduced in the dose group compared with the model group.The contents of adenosine phosphate in model rats after administration of the dose group were higher than those in model group,and the Carthami Flos-Glycyrrhizae Radix et Rhizoma group was better than that of the Carthami Flos group (P＜0.05).Conclusion:Carthami Flos and Carthami Flos-Glycyrrhizae Radix et Rhizoma herb-pair could improve the energy metabolism in rats with cold coagulation blood stasis,and the effect of Carthami Flos-Glvcvrrhizae Radix et Rhizoma was stronger than that of Carthami Flos.

目的 调查胃息肉患者的病例资料,评估胃息肉的危险因素,为胃息肉的防治提供理论依据.方法 选择2014年1月至2016年1月在西安医学院第一附属医院接受胃镜检查确诊为胃息肉的110例患者作为胃息肉组,选择同期因消化系统疾病接受胃镜检查排除胃息肉的101例患者作为对照组,回顾性分析患者的一般资料、伴有疾病、职业特点和幽门螺杆菌(Hp)检测结果等数据,采用χ2检验评估胃息肉发生发展的相关因素.结果 胃息肉组与对照组患者的性别、年龄、职业特点和Hp阳性率差异无统计学意义;胃息肉组患者中约40.91%体质量指数异常,在体质量指数异常患者中,超重和肥胖患者占82.20%;胃息肉组患者中伴有窦性心动过缓、脂肪肝、慢性胃炎和胆囊炎的患者,胃息肉发生率均高于对照组(P均<0.05).结论 胃息肉发生可能与体质量超重、伴有窦性心动过缓、脂肪肝、慢性胃炎和胆囊炎等因素相关.

目的 建立同时测定血浆中丹参素(DSS)、原儿茶酸(PA)及羟基红花黄色素A(HSYA)的HPLC分析方法,研究丹红注射液主要酚酸类成分DSS、PA以及HSYA在正常和寒凝血瘀大鼠中药代动力学行为.方法 正常及寒凝血瘀模型大鼠各6只,尾静脉注射丹红注射液.采用HPLC法检测给药后2、5、10、15、20、25、30、40、50、60、90 min时血浆中DSS、PA以及HSYA的浓度,流动相为0.2％甲酸水(A)_甲醇(B),梯度洗脱,梯度波长检测:280 nm(0～40 min),402 nm(40～60min).DAS 3.0软件计算药代动力学参数.结果 DSS和PA呈现二室开放模型,HSYA呈现三室模型.与正常组相比,模型大鼠体内DSS、PA和HSYA的达峰浓度Cmax、DSS的分布半衰期t1/2α、PA和HSYA的消除半衰期t12α(t12γ)和药时曲线下面积AUC以及总表观分布容积V均增大(P＜0.05);PA和HSYA的分布半衰期t1/2α和DSS药时曲线下面积AUC均降低(P＜0.05).结论 在寒凝血瘀病理模型下,DSS在体内分布减慢,生物利用度降低;PA和HSYA的分布加快,消除减慢,表观分布容积增大,生物利用度增加,更能发挥好疗效.

Context: To systematically evaluate the effects of hepatoprotective agents, when delivered either alone or in combination with other antiviral or non-antiviral drugs in patients with hepatitis B and hepatic fibrosis. Objectives: The current randomized controlled clinical trials aimed to evaluate the efficacy of combinations of antiviral and non-antiviral hepatoprotective agents on indexes of liver function and liver fibrosis in patients with hepatitis B. Data Sources: Published literatures in Chinese and English on hepatoprotective treatment strategies for chronic hepatitis B and liver fibrosis were searched in three databases and randomized controlled clinical trials were selected. Study Selection: Data were extracted according to a variety of inclusion and exclusion criteria. Meta-analysis was employed to analyze the data. Results: A total of 22 randomized controlled trials encompassing 1,714 cases were considered in the meta-analysis. The obtained results indicated that the combination of antiviral drug and hepatoprotective agent was better than antiviral drug alone to improve liver function. Similarly, regarding liver fibrosis, using two different hepatoprotective agents was better than using one agent. The normalization rates of Aminotransferase (ALT) and total Bilirubin (TBil) were improved 25.7% by two hepatoprotective agents compared to the single agent. Acetylcysteine was superior to ursodeoxycholic acid or silibinin to reduce ALT. Ursodeoxycholic acid was superior to acetylcysteine or silibinin to reduce TBIL. Conclusions: Hepatoprotective agents combined with antiviral drugs can significantly improve liver function and liver fibrosis parameters in patients with hepatitis B.

AIM To establish an HPLC method for simultaneously determining nine components in Lemai Capsules( Salviae miltiorrhizae Radix et Rhizome,Chuanxiong Rhizome,Paeoniae Radix rubra,Carthami Flos,Cyperi Rhizoma),including danshensu,tanshinoneⅡA,protocatechuic aldehyde,protocatechuic acid,ferulic acid,gallic acid,peoniflorin,hydroxysafflor yellow A and α-cyperone. METHODS The analysis was carried out on Agilent TC-C18column( 4. 6 mm × 250 mm,5 μm). The mobile phase consisted of methanol-0. 2% formic acid-water with step gradient elution. The flow rate was 0. 6 mL / min,the column temperature was 30 ℃ and the detection wavelengths were 230 nm,254 nm,280 nm,320 nm,and 403 nm respectively. RESULTS The samples showed a good relationship in the ranges of 5. 0 ~ 500. 0 μg / mL for danshensu,1. 0 ~ 100. 0 μg / mL for tanshinoneⅡA andα-cyperone,2. 5 ~250. 0 μg/mL for protocatechuic acid and protocatechuic aldehyde,1. 7 ~170. 0 μg/mL for ferulic acid,10. 0 ~ 1 000. 0 μg / mL for gallic acid,20. 0 ~ 2 000. 0 μg / mL for peoniflorin and 4. 6 ~ 460 μg / mL for hydroxysafflor yellow A,respectively( r≥0. 999 0). The average recoveries of the nine compoments were more than 95. 0%. CONCLUSION This method with strong specificity is simple,accurate,reproducible and can be used for quality control of Lemai Capsules.

Objective To develop a reversed phase high performance liquid chromatographic(RP-HPLC) analysis system for hydroxysafflor yellow A(HSYA) in rat model of cold coagulation and blood stasis(CCBS),and to investigate the influence of Sappan lignum on the pharmacokinetics of HSYA in CCBS rats.Methods Rat CCBS models were randomly divided into two groups with each containing 6 animals.Rats were orally given Carthami flos extract or Carthami flos extract combined with Sappan lignum(The dosage: 20.0 g/kg crud drug of Carthami flos).Plasma samples were collected in heparinized tubes from the oculi chorioideae vein at 5,10,20,30,45,60,90,120,150,210,and 270 min after drug administration;and the plasma proteins were precipitated with 20% trichloroacetic acid aqueous solution.Plasma concentrations of HSYA were detected by RP-HPLC at different time points after drug administration.The data were processed by DAS 2.0 software to calculate the pharmacokinetic parameters.Results Compared with the Carthami flos group,the pharmacokinetic parameters V1/F and CL/F of HSYA in the Carthami flos combined with Sappan lignum group were significantly decreased(P0.01),and the AUC0-t,Cmax,and t1/2α of HSYA were significantly increased(P0.01).Conclusion Sappan lignum can promote the absorption of HSYA in rat model of CCBS and reduce the distribution of HSYA,thus exercise an efficacy-enhancing effect.

AIM To establish an HPLC method for simultaneously determining danshensu,peoniflorin,puerarin,hydroxysafflor yellow A,tetramethylpyrazine and ferulic acid in Xinnaokang Capsules(Salviae miltiorrhizae Radix et Rhizoma,Paeoniae Radix rubra,Puerariae lobatae Radix,Chuanxiong Rhizoma,Carthami Flos,etc.).METHODS The analysis was performed on Agilent HC-C18 column(4.6 mm×250 mm,5 μm),and the mobile phase consisted of methanol-0.2% formic acid.The flow rate was 0.6 mL/min and detection wavelengths were set at 254 nm for peoniflorin and puerarin,280 nm for danshensu and tetramethylpyrazine,320 nm for ferulic acid and 403 nm for hydroxysafflor yellow A.RESULTS The samples showed a good relationship in the ranges of 2.5-200 μg/mL for peoniflorin,puerarin and hydroxysafflor yellow A,2.91-233 μg/mL for ferulic acid,0.81-130 μg/mL for tetramethylpyrazine and 1.66-133 μg /mL for danshensu.All of the average recoveries were more than 97%.CONCLUSION The method is accurate,reliable and reproducible and can be used for quality control of Xinnaokang Capsules.

目的建立冠心七味片中丹参素、没食子酸、原儿茶酸和原儿茶醛测定方法。方法 Agilent TC-C18色谱柱(4.6 mm×150 mm,5μm),流动相为甲醇-0.2%甲酸水线性梯度洗脱,体积流量0.7 mL/min,检测波长275 nm,柱温25℃。结果丹参素、没食子酸、原儿茶酸和原儿茶醛分别在1.25~120μg/mL(r2=0.999 8)、8.75~350μg/mL(r2=1.000 0)、4.0~250μg/mL(r2=0.999 6)和2.5~375μg/mL(r2=0.999 9)质量浓度范围内具有良好的线性关系,方法回收率分别为99.5%、96.3%、94.8%和97.5%,最低检测限分别为9.0 ng/mL、2.5 ng/mL、7.5ng/mL和4.0 ng/mL。结论本方法操作快速简便,结果准确,重复性良好,可为冠心七味片的质量控制提供一定依据。

AIM To investigate the effects of Acorus tatarinowii Schott on pharmacokinetics of danshensu,protocatechuic aldehyde and protocatechuic acid in rats with compatibility of Salvia miltrorrhiza.METHODS Aqueous extracts of Salvia miltiorrhiza and Salvia miltiorrhiza plus Acorus tatarinowii Schott were orally administered to SD rats,respectively.The protein in the blood sample was precipitated by 10% trichloroacetic acid,and was extracted with ethyl acetate.Chromatogram of rats plasma was determined by RP-HPLC.RESULTS Both extract concentrations were all fitted with the two-compartment open model.In the compatibility,plasma drug concentration-time curves and absorption rate constant for danshensu and protocatechuic acid increased under the influence of Acorus tatarinowii Schott.CONCLUSION Acorus tatarinowii Schott could promote absorption of Salvia miltiorrhiza into the blood,and increase the bioavailability of danshensu and protocatechuic acid.