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Correlation Analysis of Drug Resistance and Resistant Genotypes of Pathogenic Klebsiella peneumoniae from Racoon Dog to Fluoroquinolones 预览
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作者 Zhao Xiaocui Liu Zhiqiang +9 位作者 Luo Junfeng Yao Weiping Feng Ling Wu Tonglei Zhang Zhiqiang Bai Xue Fu Yanfang Gao Qingshan Jia Qinghui Shi Qiumei 《动物与饲料科学:英文版》 CAS 2019年第1期35-38,共4页
[Objective] The paper was to analyze the correlation between drug resistance and resistant genotypes of pathogenic Klebsiella peneumoniae from racoon dog to fluoroquinolones.[Method] The drug resistance and resistant ... [Objective] The paper was to analyze the correlation between drug resistance and resistant genotypes of pathogenic Klebsiella peneumoniae from racoon dog to fluoroquinolones.[Method] The drug resistance and resistant genes of 24 strains of pathogenic K. peneumoniae from racoon dog to fluoroquinolones were detected by K-B drug susceptibility paper and PCR.[Result] Multiple drug-resistant strains were dominant among 24 strains of pathogenic K. peneumoniae, and the drug resistance to levofloxacin, enrofloxacin, ciprofloxacin and norfloxacin was 70.8%-79.2%;the strains resistant to 4, 3 and 2 antibiotics were 58.3%, 29.2% and 8.3%, respectively. The detection rates of drug-resistant genes TEM, gyrB, parC,parE, gyrA and SHV were 75%-100%, and the number of strains carrying 9, 8, 7, 6, 4 and 3 drug-resistant genes was 4.2%-41.7%. Comparison of drug-resistant genes and drug resistance showed that the coincidence rates of levofloxacin, enrofloxacin, ciprofloxacin and norfloxacin were 78.9%-100%.[Conclusion] There were certain correlation between drug resistance and resistant genotypes of 24 strains of pathogenic Klebsiella peneumo-niae to fluoroquinolones. 展开更多
关键词 Racoon DOG KLEBSIELLA peneumoniae DRUG sensitivity test DRUG resistance DRUG-RESISTANT genotype
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药品零差率政策对吉林市不同类型医院影响分析
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作者 赵彤 胡亚男 +1 位作者 付非 钟越 《中国农村卫生事业管理》 2019年第4期265-269,共5页
目的了解药品零差率政策对吉林市医院的影响和患者满意度情况,为吉林市医院落实国家零差率政策提供理论依据和有效建议。方法收集吉林市中心医院、吉林医药学院附属医院、吉林市职业病医院等3家医院实行零差率前后就诊患者数、平均人均... 目的了解药品零差率政策对吉林市医院的影响和患者满意度情况,为吉林市医院落实国家零差率政策提供理论依据和有效建议。方法收集吉林市中心医院、吉林医药学院附属医院、吉林市职业病医院等3家医院实行零差率前后就诊患者数、平均人均费用及药占比情况并分析;通过问卷量表对3家医院就诊患者进行政策满意度调查并分析。结果药品零差率政策的实施提高了医院就诊患者数;门诊与住院部的人均费用都有所降低,医院科室的药占比呈下降趋势。结论吉林市医院应针对药品价格控制管理、基本药物目录、宣传普及政策等方面加大工作力度。 展开更多
关键词 药品 零差率政策 药占比 患者满意度
Triggers of histologically suspected drug-induced colitis 预览
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作者 Thorsten Brechmann Katharina Günther +2 位作者 Matthias Neid Wolff Schmiegel Andrea Tannapfel 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第8期967-979,共13页
BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease ... BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series.AIM To investigate potential triggers of drug-induced colitis(DiC).METHODS We conducted a retrospective,observational case control study.Patients were assigned to DiC or one of two age-and gender-matched control groups(noninflammatory controls and inflammatory colitis of another cause)based on histopathological findings.Histopathology was reassessed in a subset of patients(28 DiC with atherosclerosis,DiC without atherosclerosis and ischaemic colitis each)for validation purposes.Medical history was collected from the electronic database and patient records.Statistical analysis included chi-squared test,t-test,logistic and multivariate regression models.RESULTS Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa(7%of all screened colonoscopic biopsy samples);a total of 633 patients were included equally matched throughout the three groups(291 males,mean age:62.1±16.1 years).In the univariate analysis,DiC was associated with diuretics,dihydropyridines,glycosides,ASS,platelet aggregation inhibitors,nonsteroidal anti-inflammatory drugs(NSAIDs),statins and fibrates,and with atherosclerosis,particularly coronary heart disease,and hyperlipoproteinaemia.Echocardiographic parameters did not show substantial differences.In the multivariate analysis only fibrates[odds ratio(OR)=9.1],NSAIDs(OR=6.7)and atherosclerosis(OR=2.1)proved to be associated with DiC.Both DiC reassessment groups presented milder inflammation than ischaemic colitis.The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis.CONCLUSION Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC.Atherosclerosis and 展开更多
关键词 DRUG toxicity DRUG-INDUCED COLITIS ISCHAEMIC COLITIS Drug-associated gastrointestinal disease Atherosclerosis Colonic ISCHAEMIA Nonsteroidal antiinflammatory drugs FIBRATES
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不同剂型利福平投药后血药浓度的监测结果分析
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作者 李明武 赖明红 +3 位作者 马萌 万荣 徐源 杜朝美 《中国防痨杂志》 CAS CSCD 2019年第6期645-649,共5页
目的分析两种不同剂型利福平投药后血药浓度的监测结果,以指导临床合理用药。方法选择2016年5月至2017年6月昆明市第三人民医院结核二科收治的活动性肺结核患者130例,按照数字表法随机分为注射组(65例;利褔平采用静脉滴注的方式,0.6g/... 目的分析两种不同剂型利福平投药后血药浓度的监测结果,以指导临床合理用药。方法选择2016年5月至2017年6月昆明市第三人民医院结核二科收治的活动性肺结核患者130例,按照数字表法随机分为注射组(65例;利褔平采用静脉滴注的方式,0.6g/次,1次/d,用500ml5%葡萄糖注射液配制)和口服组(65例;利褔平采用口服的方式,0.6g/次,1次/d);利福平最低抑菌浓度(MIC)为0.39~1.56μg/ml,本研究统计达到MIC为0.39μg/ml的患者例数。口服组最终有2例患者因不同时间点血药浓度监测数据存在遗漏,故剔除,本研究最终纳入128例患者,其中注射组65例,口服组63例。两组患者用药第7天后,采集不同时间点的血浆标本,通过超高效液相色谱-串联质谱法(UPLC-MS/MS)检测两组利福平的血药浓度值。结果注射组利福平最高血药浓度出现在输注后1.5h,中位数(四分位数)[M(Q1,Q3)]为0.954(0.210,3.420)μg/ml;口服组最高血药浓度出现在服药后2h,M(Q1,Q3)为1.253(0.249,2.501)μg/ml。注射组峰值血药浓度为1.786(0.704,3.591)μg/ml,均值血药浓度为0.688(0.269,1.087)μg/ml,均高于口服组[分别为1.468(0.423,3.748)μg/ml和0.571(0.149,1.894)μg/ml],但差异均无统计学意义(Z值分别为-0.90和-0.02,P值分别为0.366和0.980);注射组谷值血药浓度为0.004(0.001,0.038)μg/ml,低于口服组[0.007(0.001,0.070)μg/ml],差异有统计学意义(Z=-8.74,P=0.000)。注射组总体达到MIC的比率为47.7%(248/520),口服组为49.4%(218/441),差异无统计学意义(χ^2=0.29,P=0.591)。结论患者采用注射和口服利福平的治疗方案,血药浓度值均较低,有超过50%的患者总体时间内并未达到MIC,无法满足利福平推荐的参考范围,可能存在剂量上的不足;应继续加强对利福平血药浓度的监测,规范使用利福平注射液。 展开更多
关键词 利福平 剂型 投药 口服 滴注 药物 药物监测 药代动力学 结果评价
急性经消化道中毒患儿临床特点及预后因素分析
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作者 郑丽娟 李小芹 +4 位作者 于静 成怡冰 王海军 王晓宇 张世玲 《中国小儿急救医学》 CAS 2019年第7期502-506,共5页
目的分析经消化道中毒患儿的临床特点,探讨中毒的防治措施.方法回顾性分析2015年1月至2017年12月郑州儿童医院急诊科收治的473例经消化道中毒患儿病例资料,对患儿年龄、发病季节、毒物种类、临床症状、实验室检查、住院费用及转归等进... 目的分析经消化道中毒患儿的临床特点,探讨中毒的防治措施.方法回顾性分析2015年1月至2017年12月郑州儿童医院急诊科收治的473例经消化道中毒患儿病例资料,对患儿年龄、发病季节、毒物种类、临床症状、实验室检查、住院费用及转归等进行分析,并将其分为药物中毒组和非药物中毒组,进行比较.结果 6 d~3岁患儿317例(67.0%),3~6岁133例(28.1%),>6岁23例(4.9%).各季节发病率相近,冬季发病率稍低.意外中毒 462 例(97.7%),非意外中毒 11 例(2.3%).药物中毒336例(71.0%),非药物中毒137例(29.0%).城市药物中毒比例高于农村,差异有统计学意义(73.8%比60.0%,χ^2 =7.037,P=0.008).非药物中毒组消化系统症状和血液系统症状比例高于药物中毒组,差异有统计学意义(54.0%比8.3%,χ^2 =120.067,P<0.001;7.3%比3.0%,χ^2 =4.491,P=0.034);非药物中毒组心血管系统症状和呼吸系统症状比例低于药物中毒组,差异有统计学意义(1.5%比14.9%,χ^2 =17.915,P<0.001;2.9%比11.0%,χ^2 =8.050,P=0.005).除肝功能、心肌酶外,非药物中毒组异常实验室指标(白细胞、血小板、血糖、乳酸、电解质、凝血)比例均高于药物中毒组,差异均有统计学意义(P均<0.05).非药物中毒组住院费用高于药物中毒组,差异有统计学意义(Z=-12.444,P<0.001).药物中毒组和非药物中毒组患儿<6 h救治组治愈或好转率均高于>6 h救治组,差异均有统计学意义(P均<0.05).结论急性经消化道中毒患儿以婴幼儿、学龄前儿童多见,以意外中毒为主,多为患儿误服.城市儿童药物中毒比例高于农村,农村儿童非药物中毒比例高于城市.非药物中毒较药物中毒对患儿损伤更严重,住院费用更高.中毒后尽早就诊是提高治愈率的重要因素. 展开更多
关键词 儿童 消化道 中毒 药物 非药物
毒品犯罪中三种行为司法定性探讨——基于最高法院纪要演进视角 预览
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作者 卢荃荃 《河南科技大学学报:社会科学版》 2019年第4期108-112,共5页
吸毒者在运输毒品过程中被查获、受以吸食为目的的购毒者委托为其介绍联络贩毒者、购买毒品人员接受贩毒者通过物流寄递方式交付毒品,是毒品犯罪中新近明确的三种犯罪行为。我国三次《毒品犯罪会议纪要》对上述问题进行了一定的解答。... 吸毒者在运输毒品过程中被查获、受以吸食为目的的购毒者委托为其介绍联络贩毒者、购买毒品人员接受贩毒者通过物流寄递方式交付毒品,是毒品犯罪中新近明确的三种犯罪行为。我国三次《毒品犯罪会议纪要》对上述问题进行了一定的解答。吸毒者在运输毒品过程中被查获与“购买、储存”行为相区别,具有一定合理性,存在改进空间;对居间介绍者受吸毒人员委托购买数量较小毒品的规制上存在不足和缺陷;购买毒品人员接受贩毒者通过物流寄递方式交付毒品分类处理具有积极意义。 展开更多
关键词 毒品 毒品犯罪 会议纪要
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Risk Control Strategy in the Research and Development of Pediatric Drugs 预览
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作者 Tang Ying Chen Yuwen 《亚洲社会药学》 2019年第3期110-118,共9页
Objective To analyze the risk control strategy in the research and development of pediatric drugs and to provide references for pharmaceutical enterprises to avoid the risks so that they can produce more and much bett... Objective To analyze the risk control strategy in the research and development of pediatric drugs and to provide references for pharmaceutical enterprises to avoid the risks so that they can produce more and much better drugs for children in China. Methods An expert questionnaire and expert interviews were conducted to identify the specific risks and the key factors, and valuable advices were put forward. Results and Conclusion There are four risk factors in the research and development of pediatric drugs. The first is that parents are concerned and they are unwilling to allow their children to participate in drug trial. Secondly, adult drug safety data cannot support pediatric drug study. Thirdly, pediatric drugs often have adverse events. Last, regulations for pediatric drugs clinical trials are not perfect. Some valuable recommendations are provided to control these risks. 展开更多
关键词 PHARMACEUTICAL ENTERPRISE RISK management PEDIATRIC DRUG DRUG research and development
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Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer 预览
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作者 Li Wei Jing-Yun Wen +4 位作者 Jie Chen Xiao-Kun Ma Dong-Hao Wu Zhan-Hong Chen Jiang-Long Huang 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第37期5590-5603,共14页
BACKGROUND Pancreatic cancer is a major cause of cancer-related death,with a 5-year overall survival rate being below 5%.The main causes of poor prognosis in pancreatic cancer include easy metastasis,high recurrence r... BACKGROUND Pancreatic cancer is a major cause of cancer-related death,with a 5-year overall survival rate being below 5%.The main causes of poor prognosis in pancreatic cancer include easy metastasis,high recurrence rate,and robust drug resistance.Gemcitabine is a first-line drug for patients with unresectable pancreatic cancer.However,due to drug resistance,the clinical effect is not satisfactory.ADAM28 is reported as a tumor promoter in some cancers,but its role in pancreatic cancer and gemcitabine chemoresistance in pancreatic cancer has not been elucidated.AIM To identify if ADAM28 can act as an important target to reverse the gemcitabine drug resistance in pancreatic cancer.METHODS RNA-sequence analysis was applied to explore the potential targets involved in the gemcitabine of pancreatic cancer.SW1990 pancreatic cancer cells were treated with an increased dose of gemcitabine,and the mRNA levels of ADAM28 were evaluated by RT-PCR.The protein and mRNA levels of ADAM28 were confirmed in the gemcitabine resistant and parallel SW1990 cells.The ADAM28 expression was also assessed in TCGA and GEO databases,and the results were confirmed in the collected tumor and adjacent normal tissues.The overall survival(OS)rate and relapse-free survival(RFS)rate of pancreatic cancer patients with high ADAM28 level and low ADAM28 level in TCGA were evaluated with Kaplan-Meier Plotter.Furthermore,the OS rate was calculated in pancreatic cancer patients with high tumor mutation burden(TMB)and low TMB.CCK-8 assay was used to examine the effect of ADAM28 on the viability of SW1990 cells.The ADAM28 and its co-expressed genes were analyzed in the cBioPortal for cancer genomics and subjected to GSEA pathway analysis.The correlations of ADAM28 with GSTP1,ABCC1,GSTM4,and BCL2 were analyzed based on TCGA data on pancreatic cancer.RESULTS RNA-sequence analysis identified that ADAM28 was overexpressed in gemcitabine-resistant cells,and gemcitabine treatment could induce the expression of ADAM28.The mRNA and protein levels of ADAM28 were el 展开更多
关键词 ADAM28 DRUG RESISTANCE OVEREXPRESSION POOR prognosis DRUG metabolism GEMCITABINE
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Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein
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作者 Jian Meng Xiao-yun Liu +11 位作者 Sheng Ma Hua Zhang Song-da Yu Yi-fan Zhang Mei-xia Chen Xiao-yu Zhu Yi Liu Ling Yi Xiao-liang Ding Xiao-yan Chen Li-yan Miao Da-fang Zhong 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第7期980-988,共9页
Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer. In this study we investigated the metabolism and disposition of pyrotinib in six healthy Ch... Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer. In this study we investigated the metabolism and disposition of pyrotinib in six healthy Chinese men after a single oral dose of 402?mg of [14C]pyrotinib. At 240?h postdose, the mean cumulative excretion of the dose radioactivity was 92.6%, including 1.7% in urine and 90.9% in feces. In feces, oxidative metabolites were detected as major drug-related materials and the primary metabolic pathways were O-depicoline (M1), oxidation of pyrrolidine (M5), and oxidation of pyridine (M6-1, M6-2, M6-3, and M6-4). In plasma, the major circulating entities identified were pyrotinib, SHR150980 (M1), SHR151468 (M2), and SHR151136 (M5), accounting for 10.9%, 1.9%, 1.0%, and 3.0%, respectively, of the total plasma radioactivity based on the AUC0–∞ ratios. Approximately 58.3% of the total plasma radioactivity AUC0–∞ was attributed to covalently bound materials. After incubation of human plasma with [14C]pyrotinib at 37?°C for 2, 5, 8, and 24?h, the recovery of radioactivity by extraction was 97.4%, 91.8%, 69.6%, and 46.7%, respectively, revealing covalent binding occurred independently of enzymes. A group of pyrotinib adducts, including pyrotinib-lysine and pyrotinib adducts of the peptides Gly-Lys, Lys-Ala, Gly-Lys-Ala, and Lys-Ala-Ser, was identified after HCl hydrolysis of the incubated plasma. Therefore, the amino acid residue Lys190 of human serum albumin was proposed to covalently bind to pyrotinib via Michael addition. Finally, the covalently bound pyrotinib could dissociate from the human plasma protein and be metabolized by oxidation and excreted via feces. 展开更多
关键词 pyrotinib EGFR/HER2 dual TYROSINE kinase inhibitor breast cancer DRUG METABOLISM DRUG DISPOSITION human plasma COVALENT binding
Characteristics of β-oxidative and reductive metabolism on the acyl side chain of cinnamic acid and its analogues in rats
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作者 Kai-jing Zhao Yang Chen +11 位作者 Shi-jin Hong Yi-ting Yang Jiong Xu Han-yu Yang Liang Zhu Ming Liu Qiu-shi Xie Xian-ge Tang Ting-ting Yang Ya-qian Zhou Li Liu Xiao-dong Liu 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第8期1106-1118,共13页
Cinnamic acid and its analogues (pyragrel and ozagrel) undergo chain-shortened (β-oxidative) and reductive metabolism on acyl side chain. In this study, we characterized the β-oxidative and reductive metabolism on a... Cinnamic acid and its analogues (pyragrel and ozagrel) undergo chain-shortened (β-oxidative) and reductive metabolism on acyl side chain. In this study, we characterized the β-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues using primary rat hepatocytes, hepatic mitochondrial, and microsomal systems. A compartmental model including parent compounds and metabolites was developed to characterize in vivo β-oxidative and reductive metabolism following an intravenous dose of parent compounds to rats. The ?tted total in vivo clearance values were further compared with the in vitro values predicted by the well-stirred model. We showed that hepatic microsomal CYP450s did not catalyze β-oxidative or reductive metabolism of the three compounds. Similar to β-oxidation of fatty acids,β-oxidative metabolism on their acyl side chain occurred mainly in mitochondria, which was highly dependent on ATP, CoA and NAD+. Fatty acids and NADH inhibited the β-oxidative metabolism. Reductive metabolism occurred in both mitochondria and microsomes. Reduction in mitochondria was ATP-, CoA-, and NAD(P)H-dependent and reversible, which was suppressed by enoyl reductase inhibitor triclosan. Reduction in microsomes was ATP-, CoA-, and NADPH-dependent but little affected by triclosan. Both plasma concentrations of β-oxidative metabolites and reductive metabolites were successfully ?tted using the compartmental model. The estimated total in vivo clearance values were consistent with those predicted from hepatocytes and organelles, implicating signi?cance of in vitro kinetics. These ?ndings demonstrate the roles of hepatic mitochondria and microsomes in β-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues along with their metabolic characteristics. 展开更多
关键词 ANTIPLATELET DRUG cinnamic acid pyragrel OZAGREL DRUG METABOLISM hepatocytes mitochondria MICROSOMES pharmacokinetics in vitro-in vivo correlation
Brain activity of anandamide:a rewarding bliss?
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作者 Maria Scherma Paolo Masia +3 位作者 Valentina Satta Walter Fratta Paola Fadda Gianluigi Tanda 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第3期309-323,共15页
Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors.These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol,the psych... Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors.These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol,the psychoactive ingredient in Cannabis sativa.Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry.Several reports suggest its involvement in the addiction-producing actions of other abused drugs,and it can also act as a behavioral reinforcer in animal models of drug abuse.Importantly,all these effects of anandamide appear to be potentiated by pharmacological inhibition of its metabolic degradation.Enhanced brain levels of anandamide after treatment with inhibitors of fatty acid amide hydrolase,the main enzyme responsible for its degradation,seem to affect the rewarding and reinforcing actions of many drugs of abuse.In this review,we will provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of anandamide,with a particular emphasis on its motivational/reinforcing properties.We will also discuss how modulation of anandamide levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmaco-therapeutic tools for the treatment of substance use disorders. 展开更多
关键词 ENDOCANNABINOIDS 2-AG ANANDAMIDE CANNABINOID receptor brain reward DRUG use disorder DRUG addiction FAAH COCAINE morphine nicotine alcohol
血常规危急值与药品不良反应的相关性研究
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作者 林筱青 《中国校医》 2019年第5期367-369,共3页
目的通过研究临床危急值与药品不良反应(ADR)相关性,提高ADR上报质量。方法抽查检验科报告的危急值项目,对涉及出现临床危急值患者的病例进行跟踪分析,对不良反应、用药情况进行调查。结果共抽查1 238个临床危急值对应病例,共发现36例疑... 目的通过研究临床危急值与药品不良反应(ADR)相关性,提高ADR上报质量。方法抽查检验科报告的危急值项目,对涉及出现临床危急值患者的病例进行跟踪分析,对不良反应、用药情况进行调查。结果共抽查1 238个临床危急值对应病例,共发现36例疑似ADR报告,占调查期间总上报ADR例数的21.43%;主要ADR表现为白细胞减少(占63.89%),其次是血小板减少和肝功能异常(均占16.67%);给药途径主要为静脉滴注和口服用药(分别占为58.33%和50.00%),涉及品种以抗菌药物、质子泵抑制剂和卡马西平为主。结论对临床危急值的监测有助于预测ADR报告质量的提高。 展开更多
关键词 临床危急值 药物 不良反应
Utilizing gastric cancer organoids to assess tumor biology and personalize medicine 预览
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作者 Miranda Lin Mei Gao +1 位作者 Michael J Cavnar Joseph Kim 《世界胃肠肿瘤学杂志:英文版(电子版)》 CAS 2019年第7期509-517,共9页
While the incidence and mortality of gastric cancer (GC) have declined due to public health programs, it remains the third deadliest cancer worldwide. For patients with early disease, innovative endoscopic and complex... While the incidence and mortality of gastric cancer (GC) have declined due to public health programs, it remains the third deadliest cancer worldwide. For patients with early disease, innovative endoscopic and complex surgical techniques have improved survival. However, for patients with advanced disease, there are limited treatment options and survival remains poor. Therefore, there is an urgent need for more effective therapies. Since novel therapies require extensive preclinical testing prior to human trials, it is important to identify methods to expedite this process. Traditional cancer models are restricted by the inability to accurately recapitulate the primary human tumor, exorbitant costs, and the requirement for extended periods of development time. An emerging in vitro model to study human disease is the patient-derived organoid, which is a three-dimensional system created from fresh surgical or biopsy tissues of a patient’s gastric tumor. Organoids are cultured in plastic wells and suspended in a gelatinous matrix, providing a substrate for extension and growth in all dimensions. They are rapid-growing and highly representative of the molecular landscape, histology, and morphology of the various subtypes of GC. Organoids uniquely model tumor initiation and growth, including steps taken by normal stomach cells to transform into invasive, intestinal-type tumor cells. Additionally, they provide ample material for biobanking and screening novel therapies. Lastly, organoids are a promising model for personalized therapy and warrant further investigation in drug sensitivity studies for GC patients. 展开更多
关键词 ORGANOIDS Gastric CANCER CANCER models DRUG sensitivity DRUG screening PERSONALIZED MEDICINE
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药品注册标准初探 预览
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作者 吴承云 黄玮 刘美君 《中国药事》 CAS 2019年第5期578-581,共4页
目的:探究药品注册标准的内涵和外延。方法:采用认识分析方法,通过对质量及药品质量认识,论述分析药品质量的实质、药品质量指标、药品标准组成及相关要求、药品标准在药品生命周期各环节作用,研讨药品注册标准的内涵与外延,以及对提高... 目的:探究药品注册标准的内涵和外延。方法:采用认识分析方法,通过对质量及药品质量认识,论述分析药品质量的实质、药品质量指标、药品标准组成及相关要求、药品标准在药品生命周期各环节作用,研讨药品注册标准的内涵与外延,以及对提高药品质量的促进作用。结果:药品质量的实质是药品临床应用的安全性和有效性,药品标准由药品代用质量指标及检验方法和有关要求组成,并在一定程度上关联药品的有效性和安全性。结论:药品注册标准具有国家标准和企业标准属性,其企业标准属性,在适应企业生产条件和追求质量差异、促进质量提高方面有其独特的作用,但标准管理及适用等尚需建立药品标准管理与评价制度,以构建和完善药品标准体系。 展开更多
关键词 药品 质量 标准 药品注册标准
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Overcoming chemotherapy resistance via simultaneous drug-efflux circumvention and mitochondrial targeting
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作者 Minglu Zhou Lijia Li +4 位作者 Lian Li Xi Lin Fengling Wang Qiuyi Li Yuan Huang 《药学学报:英文版》 CSCD 2019年第3期615-625,共11页
Multidrug resistance(MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here,based on the previous research of... Multidrug resistance(MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here,based on the previous research of N-(2-hydroxypropyl)methacrylamide(HPMA) polymer–drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin(Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide(MPP) and then attached to(HPMA) copolymers(P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells via endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species(ROS) as well as reduction of adenosine triphosphate(ATP)production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery. 展开更多
关键词 DRUG resistance P-gp pumps MITOCHONDRIAL targeting HPMA COPOLYMER DRUG delivery DOXORUBICIN
Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis
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作者 Yuan-qiang Wang Wei-wei Lin +5 位作者 Nan Wu Si-yi Wang Mao-zi Chen Zhi-hua Lin Xiang-Qun Xie Zhi-wei Feng 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第9期1138-1156,共19页
Serotonin (5-HT) receptors are proteins involved in various neurological and biological processes, such as aggression, anxiety, appetite, cognition, learning, memory, mood, sleep, and thermoregulation. They are common... Serotonin (5-HT) receptors are proteins involved in various neurological and biological processes, such as aggression, anxiety, appetite, cognition, learning, memory, mood, sleep, and thermoregulation. They are commonly associated with drug abuse and addiction due to their importance as targets for various pharmaceutical and recreational drugs. However, due to a high sequence similarity/identity among 5-HT receptors and the unavailability of the 3D structure of the different 5-HT receptor, no report was available so far regarding the systematical comparison of the key and selective residues involved in the binding pocket, making it difficult to design subtype-selective serotonergic drugs. In this work, we first built and validated three-dimensional models for all 5- HT receptors based on the existing crystal structures of 5-HT1B, 5-HT2B, and 5-HT2C. Then, we performed molecular docking studies between 5-HT receptors agonists/inhibitors and our 3D models. The results from docking were consistent with the known binding affinities of each model. Sequentially, we compared the binding pose and selective residues among 5-HT receptors. Our results showed that the affinity variation could be potentially attributed to the selective residues located in the binding pockets. Moreover, we performed MD simulations for 12 5-HT receptors complexed with ligands;the results were consistent with our docking results and the reported data. Finally, we carried out off-target prediction and blood–brain barrier (BBB) prediction for Captagon using our established hallucinogen-related chemogenomics knowledgebase and in-house computational tools, with the hope to provide more information regarding the use of Captagon. We showed that 5-HT2C, 5-HT5A, and 5-HT7 were the most promising targets for Captagon before metabolism. Overall, our findings can provide insights into future drug discovery and design of medications with high specificity to the individual 5-HT receptor to decrease the risk of addiction and prevent drug abuse. 展开更多
关键词 5-HT RECEPTOR MOLECULAR docking MOLECULAR dynamics simulation SYSTEMS PHARMACOLOGY analysis off-target prediction DRUG abuse and addiction DRUG selectivity Captagon
药品生产批号及有效期标注方式标准化研究 预览
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作者 林卡娜 施芳红 +3 位作者 李浩 黄诗颖 张顺国 陈敏玲 《中国药业》 CAS 2019年第1期85-87,共3页
目的为我国药品生产批号及有效期规范化管理提供参考。方法统计上海交通大学医学院附属上海儿童医学中心所有药品的生产批号及有效期印制方式,并进行汇总分析。针对日常药品生产批号及有效期管理中遇到的问题,提出规范化改进建议。结果... 目的为我国药品生产批号及有效期规范化管理提供参考。方法统计上海交通大学医学院附属上海儿童医学中心所有药品的生产批号及有效期印制方式,并进行汇总分析。针对日常药品生产批号及有效期管理中遇到的问题,提出规范化改进建议。结果医院药品生产批号及有效期印制方式以墨印(占44.31%)和钢印(占39.07%)为主;印制位置以包装开口处为主(占72.16%);药品有效期以“月”表示的占66.32%,15种药品以“有效期至(Exp.)”表示,现有药品有效期表示方式易产生歧义。结论我国现有药品生产批号及有效期制度需进行优化及细化。 展开更多
关键词 药品 生产批号 有效期 标注方式 标准化 药品监管
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继续小剂量阿司匹林联合雷贝拉唑对消化性溃疡愈合的影响
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作者 肖清华 蔡达兴 房太勇 《中国基层医药》 CAS 2019年第5期583-586,共4页
目的探讨阿司匹林相关性消化性溃疡出血止血后,继续小剂量阿司匹林联合雷贝拉唑对消化性溃疡愈合的影响,并探讨与溃疡愈合失败相关的独立因素。方法收集福建医科大学附属第二医院2016年6月至2018年6月收治的阿司匹林引起上消化道溃疡出... 目的探讨阿司匹林相关性消化性溃疡出血止血后,继续小剂量阿司匹林联合雷贝拉唑对消化性溃疡愈合的影响,并探讨与溃疡愈合失败相关的独立因素。方法收集福建医科大学附属第二医院2016年6月至2018年6月收治的阿司匹林引起上消化道溃疡出血患者138例的临床资料,患者经治疗无再活动性出血后采用随机数字表法分为两组,阿司匹林组(n=68)接受阿司匹林100 mg/d加雷贝拉唑80 mg/d治疗8周,安慰剂组(n=70)采用雷贝拉唑80 mg/d加安慰剂治疗8周。对有幽门螺杆菌感染的受试者用标准四联疗法治疗。观察两组消化性溃疡的愈合情况。结果阿司匹林组溃疡愈合率79.4%(54/68),安慰组溃疡愈合率84.3%(59/70),两组差异无统计学意义(χ^2=0.552,P>0.05);阿司匹林组和安慰剂组各有5例溃疡再出血,再出血率分别为7.4%(5/68)和7.1%(5/70),两组差异无统计学意义(χ^2=0.002,P>0.05)。影响阿司匹林相关消化性溃疡愈合的因素中,愈合率与治疗期间使用类固醇(χ^2=6.135,P=0.041)和吸烟(χ^2=5.616,P=0.018)显著相关,其他因素包括年龄、高血压、糖尿病、饮酒、既往溃疡出血史、初始幽门螺杆菌状态和溃疡位置均未影响溃疡的愈合。结论阿司匹林相关性消化性溃疡出血后,继续小剂量阿司匹林联合雷贝拉唑并不影响消化性溃疡的愈合,而使用类固醇、饮酒和吸烟是影响溃疡愈合的独立危险因素。 展开更多
关键词 剂量效应关系 药物 阿司匹林 非甾体类抗炎药 雷贝拉唑 药物疗法 联合 消化性溃疡出血 消化性溃疡 危险因素
Exploring the utility of the Chasing Principle:influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040in aqueous suspension
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作者 Scheyla Daniela Siqueira Jorgensen Thomas Rades +2 位作者 Huiling Mu Kirsten Graeser Anette Müllertz 《药学学报:英文版》 CSCD 2019年第1期194-201,共8页
This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol(CAR), cinnarizine(CIN) or R3040 on drug solubilization in a twocompartment in vitro lipolysis mo... This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol(CAR), cinnarizine(CIN) or R3040 on drug solubilization in a twocompartment in vitro lipolysis model. Correlation of drug log P or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1(1:1, w/w) and Kolliphor RH40, with ethanol at 10%(w/w) were used. SNEDDS were named F65, F55 and F20(numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS(F0) were also analyzed. While the ranking order of drug solubilization was F65? F55? F204F0 for CAR;F65? F554F204F0 for CIN and F65? F55? F204F0 for R3040-with higher CAR solubilization than for R3040 and CIN-the ranking of Seqof CAR, CIN and R3040 in SNEDDS was F65 o F55o F20, F65? F554F20 and F654F554F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high Seq in SNEDDS did not reflect high drug solubilization. As CAR(log P 3.8) showed higher solubilization than CIN(log P 5.8) and R3040(log P 10.4), a correlation between drug log P and drug solubilization was observed. 展开更多
关键词 Self-nanoemulsiying DRUG delivery system(SNEDDS) Chasing PRINCIPLE Two-compartment in vitro LIPOLYSIS Rat gastrointestinal conditions DRUG SOLUBILIZATION
Repurposing drugs to target nonalcoholic steatohepatitis 预览
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作者 Silvia Sookoian Carlos J Pirola 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第15期1783-1796,共14页
Nonalcoholic fatty liver disease (NAFLD) is a complex disorder that has evolved in recent years as the leading global cause of chronic liver damage. The main obstacle to better disease management pertains to the lack ... Nonalcoholic fatty liver disease (NAFLD) is a complex disorder that has evolved in recent years as the leading global cause of chronic liver damage. The main obstacle to better disease management pertains to the lack of approved pharmacological interventions for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-fibrosis-the severe histological forms. Over the past decade, tremendous advances have been made in NAFLD research, resulting in the discovery of disease mechanisms and novel therapeutic targets. Hence, a large number of pharmacological agents are currently being tested for safety and efficacy. These drugs are in the initial pharmacological phases (phase 1 and 2), which involve testing tolerability, therapeutic action, and pharmacological issues. It is thus reasonable to assume that the next generation of NASH drugs will not be available for clinical use for foreseeable future. The expected delay can be mitigated by drug repurposing or repositioning, which essentially relies on identifying and developing new uses for existing drugs. Here, we propose a drug candidate selection method based on the integration of molecular pathways of disease pathogenesis into network analysis tools that use OMICs data as well as multiples sources, including text mining from the medical literature. 展开更多
关键词 DRUG discovery DRUG REPOSITIONING FIBROSIS GENETICS Treatment Systems BIOLOGY
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