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  • Menglu FU,Ruolan DONG,Ling TU,Xizhen XU
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    Clopidogrel is one of the anti-platelet drugs, which is widely used in the world.It plays an important role in the treatment of patients with acute coronary syndrome and those undergoing percutaneous coronary intervention.Clopidogrel is effective in inhibiting the activity of platelets, decreasing the incidence of thrombosis in the stent, and then reducing the risk of adverse cardiovascular events in affected individuals.However, some patients still have coronary thrombosis after taking clopidogrel.This phenomenon is known as clopidogrel resistance or clopidogrel non-response or low response.Identification of clopidogrel resistance is of great significance in preventing the occurrence of adverse cardiovascular events.This paper provides guidance for the clinical treatment of clopidogrel resistance by discussing the definition, mechanisms and laboratory evaluation of clopidogrel resistance.

  • Cheng CHEN,Yin HUANG,Jiao YANG,Yong YANG
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    Through exploring the role of placental endocrine,the relationship between placental endocrine changes and certain disease states,and the relationship between placental endocrine and rational use of drugs commonly used in pregnancy were summarized.Placental hormones play an important role during pregnancy.Placental endocrine abnormality can cause some diseases that may need drug treatment.Besides,some drugs also can affect the placenta endocrine,resulting in adverse pregnancy outcomes.Drug safety during pregnancy requires the consideration of the interaction between medicine and placenta endocrine.

  • Jingyi ZHANG,Shuxian LIN,Lisheng LI,Qin WU,Ansheng SUN
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    Objective To investigate the inhibition of rutaecarpine (Rut) on left ventricular hypertrophy rat induced by abdominal aorta coarctation (AAC) and further explore the potential mechanisms. Methods Left ventricular hypertrophy was induced by AAC in male Sprague-Dawley rats.Fifty rats were randomly divided into five groups:model control group,sham operation group,low-,middle- and high-dose (10,20,40 mg·kg-1·d-1) Rut group,with 10 rats of each group.Rut was administrated by gavage once daily from the first day after operation for consecutive 4 weeks.The sham operation and model groups were administrated with equal volume of 0.9% sodium chloride solution.The hemodynamics parameters were detected by BL-420 E biology function laboratory system,and the left ventricular hypertrophy index (LVHI,left ventricular weight/body weight) was measured at 8 h after administration of the last dose.The pathological changes of left ventricular hypertrophy were evaluated by HE staining.To elucidate the mechanism of protection,the mRNA expressions of atrial natriuretic factor (ANF),extracellular signal-regulated kinase 2 (ERK2) and MAPK phosphatase-1 (MKP-1) were analyzed by real time RT-PCR,and the protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. Results Left ventricular hypertrophy induced by AAC was evidenced by the increased left ventricular weight (LVW) and LVHI (P<0.01),the decreased± dp/dt max (P<0.01),and the elevated expression of ANF (P<0.01).Compared with model control,Rut (20,40 mg·kg-1·d-1) treatment significantly attenuated AAC-induced rat left ventricular hypertrophy,decreased the LVHI (P<0.05),left ventricular systole pressure (LVSP),and left ventricular end diastolic pressure (LVEDP) (P<0.05),and increased ±dp/dtmax(P<0.01).In addition,Rut (20,40 mg·kg-1·d-1) downregulated the expression of ANF,ERK2 mRNA,and ERK2 protein,but upregulated the MKP-1 mRNA and protein expression.However,Rut low-dose (10 mg·kg-1·d-1) was ineffective (P>0.05). Conclusion Rut alleviates left ventricular hypertrophy induced by abdominal aorta coarctation,and the protection appears to be due,at least in part,to its inhibitory effects on the MAPK/ERK signal pathway.

  • Xianshun XU,Huabin HUANG,Zhongxian WAN,Yuancheng LUO,Fei WU,Yuancui XU
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    Objective To investigate the effect of effective fractions from Radix Vitis Davidii Foex. on fracture healing. Methods SD rats were randomly divided into model control group,Yunnan Baiyao group,and effective fraction group (n=36 each group).Fracture models were established.Rats in the Yunnan Baiyao group and effective fraction group were given 3.0 g·kg-1·d-1 of Yunnan Baiyao and effective fraction from Radix Vitis Davidii Foex.,respectively,and rats in the model control group was treated with the same volume of pure water.Alkaline phosphatase and Ca concentration in serum were determined.For radius fracture structure,digital radiography and RT-PCR detection of VEGF mRNA expression were performed. Results The peak concentration of the alkaline phosphatase and Ca concentration in serum were significantly higher in the effective fraction group than in the Yunnan Baiyao group,and peak value appeared earlier,fracture healing score was higher,fracture line disappeared earlier,and VEGF mRNA expression was significantly higher in three weeks after the fracture (all P<0.01) . Conclusion The effect of the effective fraction from RadixVitis Davidii Foex.on the fracture healing is strong.

  • Lina ZHANG,Xiaoya MA,Sha LI,Li ZHANG
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    Objective To establish a method for the determination of 10-hydroxyl carbamazepine (MHD),which is an activity metabolite of oxcarbazepine in human serum. Methods Serum samples were detected by high performance liquid chromatography (HPLC) after being processed by methanol protein deposition.The chromatographic column was Agilent TC-C18 (4.6 mm×250 mm,5 μm),with the mobile phase of acetonitrile-10 mmol·L-1 KH2PO4 (33:67) at a flow rate of 1.0 mL·min-1.The detection wavelength was 230 nm,and phenacetin was used as an internal standard. Results The average recovery range of low,middle and high (1.0,10.0,60.0 μg·mL-1) concentrations for MHD was from 100.3% to 106.0%.The RSD of intra-day and inter-day was ≤5.8% (n=5) and ≤7.4% (n=5),respectively.The limit detection of analysis method was 0.1 μg·mL-1.Regression equation was Y=0.130 8X+0.067 9 (r=0.996 6,n=5).Serum samples remained stable at room temperature,freezing and freeze thawing condition. Conclusion This method is sensitive,accurate,simple and quick,and can be used for monitoring the oxcarbazepine metabolites MHD in serum for clinical and pharmacokinetic study.

  • Guozhu HAN,Zeyao TANG
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    Phosphocreatine (PCr),a natural high energy phosphate,plays a pivotal role in maintaining energy homeostasis of the body.Exogenous PCr has been developed as a cardio-protective drug and extensively used in treatment of cardiovascular diseases.PCr has special chemical structure,which confers much bioinformation on it,and becomes a multitarget-directed drug.Since the 21st century,with rapid development of molecular biology,the multiple target action mechanisms of PCr have continually gained elucidation,including energy-related and non-energy-related mechanisms,intracellular and extracellular mechanisms,which are leading to its extensive clinical applications in cardiovascular diseases.Based on author’s research and published literatures,this article reviews the research progress in multiple target action mechanisms of PCr,including energy supply,membrane stabilization,anti-platelet aggregation,electrophysiology,enzyme inhibition and protection of mitochondria,antiapoptotic effect,etc.

  • Chen CHEN,Xiaomei GUO
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    Hypertension is closely related to the formation of aortic dissection.Long-term effects of hypertension on the vessel wall can cause lesions of the aortic wall.Under the influence of various factors, the vascular structure is easy to be affected by hypertension, leading to tearing injury.This article mainly discuss the pathogenesis of aortic dissection by hypertension from three aspect:the hemodynamics, histopathology and inflammatory immunology.

  • Yue CHENG,Xi WANG
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    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly discovered serine protease belonging to the pro-protein family.After being synthesized and secreted by the liver, PCSK9 can be transported in conjunction with low density lipoprotein receptor (LDLR) on the cell surface into lysosomes for degrading LDLR, so that the plasma level of low density lipoprotein cholesterol (LDL-C) failed to be degraded due to the receptor deficiency, which resulted in a rise in plasma LDL-C.PCSK9 inhibitors can effectively inhibit the function of PCSK9 to reduce the level of blood lipids suggested a therapeutic target for the treatment of hypercholesterolemia, which can not only reduce the incidence of cardiovascular events together with the adverse reactions, but also can reverse the development of atherosclerosis and coronary heart disease.This review mainly states that the discovery of PCSK9 targets, the function of PCSK9, and the current status of major PCSK9 inhibitors.

  • Xiangyu XU,Xiaomei GUO
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    Although great progress has been made in the treatment of heart failure,refractory heart failure is still a difficult problem.It has high incidence and poor prognosis,which brings huge financial burden to patients, families and society.Recently,the clinical application of sacubitril/valsartan and ivabradine,mechanical circulatory support,and heart transplantation have been greatly improved.This article reviews current treatments of refractory heart failure from aspects of new breakthroughs in drug treatment,mechanical circulatory support,and heart transplantation.

  • Yihao MO,Xuesong HU
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    Objective To investigate the correlation between Paraoxonase-1 (PON-1) gene Q192R polymorphism and clopidogrel resistance (CR). Methods A total of 118 patients with coronary artery disease diagnosed by coronary angiography or coronary artery CT angiography were enrolled.Platelet aggregation rate was assessed by ADP-induced light-transmittance aggregometry after the patients received adequate clopidogrel pretreatment.The patients were divided into (clopidogrel resistance group (CR group) and non-clopidogrel resistance group (NCR group) according to the ADP-induced platelet aggregation rate.The gene of Q192R was detected by MassARRAY Time of Flight Mass Spectrometry.The genotypes and allele frequencies between the two groups were compared. Results According to the ADP-induced platelet aggregation rate,25 patients were defined as clopidogrel resistant and 93 as non-clopidogrel resistant.The incidence of clopidogrel resistance was 21.2%.Three frequencies of genotype RR,QR and QQ were 36.0%,52.0% and 12.0% in CR group,and 32.2%,57.0% and 10.8% in NCR group,respectively.The frequencies of Q and R allele in CR group were 62.0% and 38.0%,and those in NCR group were 60.8% and 39.2%.No significant differences in genotype and allele frequency were found between CR group and NCR group (P>0.05). Conclusion The PON-1 gene Q192R polymorphism is not associated with clopidogrel resistance in patients with CHD.

  • Jiping HUO,Jingchen TIAN,Zhigang ZHAO,Shenghui MEI,Xingang LI,Kefu YU
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    Aromatic antiepileptic drugs such as carbamazepine are the first-line treatment for epilepsy.The adverse reactions have greatly limited their clinical application.The occurrence rate of severe skin adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is low,but they are often fatal.Human leukocyte antigen (HLA) gene polymorphisms are reported to be related with skin adverse reactions caused by aromatic antiepileptic drugs,but the exact mechanism is unclear.This article will perform a review about the correlation between skin adverse reactions caused by aromatic antiepileptic drugs and HLA gene polymorphisms published in recent years,in order to provide theoretical basis for further study of HLA susceptibility genes in Chinese Han population,and provide a reference for achieving individualized treatment of epilepsy.

  • Jianming LIU,Zijin XU,Yuxiu YANG,Fang WANG,Fen LIU
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    Objective To prepare scutellarin liposomes and to investigate the pharmacokinetics in rats. Methods The liposomes of scutellarin coated with carbopol were prepared with the film dispersion method.Minicolumn centrifugation method was applied to measure the encapsulation efficiency (EE) before and after coating.SD rats were randomly divided into three groups,which were given intragastric administration of scutellarin suspension,scutellarin liposomes,and carbopol-coated scutellarin liposomes,respectively.And then the pharmacokinetic parameters were compared. Results Carbopol-coated scutellarin liposomes after intragastric administration in rats showed pharmacokinetic characteristics of two-compartment model.The main pharmacokinetic parameters of scutellarin suspension,scutellarin liposomes,and carbopol-coated scutellarin liposomes were as follows:AUC0-∞ (50.03±13.45) μg·h·mL-1,(78.99±20.28) μg·h·mL-1,and (107.97±27.26) μg·h·mL-1,respectively. Conclusion After coated liposomes,the oral bioavailability of scutellarin 1iposomes can be significantly improved,and the maximum drug concentration also increased.

  • Mutu HUANG,Xinmin XIE,Mei ZHANG,Lanlan LIN,Liping HAN
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    Objective To establish a method for isoimperatorin in Fengshi Bitong capsule and to study the effects of different doses of 60Co irradiation on the content of isoimperatorin. Methods The Agilent C18 column(4.6 mm×150 mm, 5 μm) was used with the mobile phase consisted of acetonitrile -water (41:59) ;The flow rate was 1.0 mL·min-1,the detection wavelength was at 310 nm,and the column temperature was at 30 ℃. Results Isoimperatorin showed a good linear relationship within a range of 3.668 96-183.448 μg· mL-1 ( r=1.000 0).The average rate of recovery was 96.42%, RSD=2.61%.The content of isoimperatorin in Fengshi Bitong capsule did not change significantly when irradiated by 2, 5 and 10 kGy of 60Co. Conclusion The established methods can be used for isoimperatorin determination in Fengshi Bitong capsule with high specificity,accuration and feasibility.The influence was not significant when the irradiation dose was less than 10 kGy.

  • Hui HU,Lin LONG,Chongyang LIU,Xianzhi LI,Zhinan MEI
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    Objective To establish the quality standards for salt eucommia dispensing granules. Methods The extractives were obtained by alcohol extraction method.HPLC was applied for the determination of pinoresinol diglucoside in dispensing granules.HPLC fingerprints were established by the contrast of Agilent 1260 HPLC,Waters HPLC and various chromatogram column. Results Pinoresinol diglucoside showed a good linear relationship (Y=2.959 4X+3.282 5,R2=0.999 9) at 102.8-2 056.0 mg·L-1 with average recovery of 99.85% (RSD=0.31%,n=9). Conclusion The method is easy-operated and accurate,which has a good specificity for the quality control of common salt eucommia dispensing granules.

  • Suqin HE,Xiaoxiao WANG,Yuchang XU
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    Objective To evaluate the measurement uncertainty of flavonoids in loquat honey by UV spectrophotometry. Methods Through analyzing the whole process of the total flavonoids in loquat honey by UV spectrophotometry detection,the mathematical model was established,the uncertainty factors were determined,and each uncertainty was evaluated.Then the combined uncertainty was calculated and the expanded uncertainty of the measurement results at the 95% confidence interval was given. Results The measurement uncertainty of the totle flavonoids content in loquat honey by UV spectrophotometry was (38.497±5.674) μg·g-1. Conclusion The uncertainty evaluation method is suitable for determination of the total flavonoids in loquat honey by UV method,and the uncertainty is mainly introduced by preparation of reference stock solution and standard curve fitting.

  • Orginal Article
  • Orginal Article
    Song WANG,Yanfen RONG
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    Objective To compare the percutaneous absorption of experimentally prepared mupirocin ointment and commercially sold mupirocin ointment,and to study the dynamics mode of transdermal absorption of mupirocin ointment. Methods Inerstil ODS-SP column (4.6 mm×150 mm,5 μm) was used with a mixture of 0.1 mol·L-1 sodium dihydrogen phosphate buffer solution (pH value was adjusted to 6.3 by 0.1 mol·L-1 sodium hydroxide solution) and acetonitrile (75:25) as a mobile phase by HPLC.The detection wavelength was set at 230 nm.The flow rate was 1.0 mL·min-1.Improved Franz type diffusion cells were used for in vitro permeation studies and excised Obama Suckling pig skins in vitro were used as the transdermal barrier.The concentration of the receptor solution was determined by HPLC to investigate its cumulative permeation quantities at different time and the two sets of ointment were compared. Results The average recovery rate of hydrophilic medium was 99.4%,and RSD was 1.2%(n=9).The average recovery rate of lipophilic medium was 99.0%,and RSD was 1.3%(n=9).There was no significant difference of the concentration between two ointment within 12 h.The osmotic release of the drug of the sample and the reference preparation, which were in hydrophilic medium, was similar to that of the Zero equation, and roughly Higuchi equation in the lipophilic medium. Conclusion The results showed that the release behavior of mupirocin ointment followed Zero equation in the hydrophilic medium,and Higchi equation in the lipophilic medium.

  • Xiaojing CAI,Hua ZHANG,Haiyan SHI,Chengbo ZHANG,Nan XU
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    Objective To study the optimum technological conditions of macroporous resin separation and purification of polyphenol composition. Methods Fingerprint of Ilex paraguariensis was established by HPLC method.The best resin,loading conditions and elution requirements were screened with chlorogenic acid and elution rate of total active constituents served as the index. Results The optimum technological conditions were as follows:the separation carrier was D101 macroporous resin,the concentration of the sample liquid was 0.10 g·mL-1,the resin adsorption quantity of crude drugs was 1.5 g·g-1,the impurity was removed by four times of amount of water at first,and then eluted with four times the amount of 70% ethanol in a gradient manner.After purification,the elution rate of chlorogenic acid was up to 82.83%,and the elution rate of total effective component was about 72.48%.The resemblance of HPLC fingerprint was over 0.98,and the components were balancedly recoveried. Conclusion The purification process of total polyphenols in Ilex paraguariensis by D101 macroporous resin was simple,reliable,and can be used for large-scale production.

  • Shuo XU,Wenfeng XU,Xuejun WU,Pengfei JIN
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    Objective To develope a high performance liquid chromatography (HPLC) method for simultaneous determination of benzoic acid and salicylic acid in compound benzoic acid embrocation. Methods An Alltima C18 column (150 mm×4.6 mm,5 μm) was used for the separation, with methanol-0.1% phosphoric acid (50:50) as the mobile phase at the flow rate of 1.0 mL·min-1.The detection wavelength was set at 236 nm.The column temperature was 35 ℃. Results The good linearity was obtained with the correlation coefficient (r) of 1.000 0 for benzoic acid and salicylic acid;the precisions and stability were satisfactory, and the relative standard deviations (RSDs) were less than 0.3%.The average recoveries (n=9) were 100.15% and 99.85% for benzoic acid and salicylic acid, respectively. Conclusion The established method is accurate, simple and rapid, and can be utilized for the simultaneous determination of benzoic acid and salicylic acid in compound benzoic acid embrocation.

  • Sisi REN,Wei XU,Hua MING
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    Objective To evaluate efficacy and safety of fluoxetine in comparison with placebo in children and adolescents with depression. Methods Randomized controlled trials (RCTs) on fluoxetine were searched in CBM,Wangfang,VIP,CNKI,PubMed,EMbase,Ovide and Cochrane Library from inception to October 2016 by computer.The pooled mean difference and relative risk were assessed by Meta analysis with RevMan 5.0 software. Results A total of 8 RCTs were included for the final analysis.Curative effect analysis showed:in Children's Global Assessment Scale [MD=3.91,95%CI(1.66,6.16),P=0.000 7] and Children’s Depression Inventory [MD=-1.98,95%CI(-3.40,-0.57),P=0.006],fluoxetine exerted a good effect in treating children’s depression.Fluoxetine was equivalent to placebo in safety. Conclusion This study supports the conclusion that the benefits of fluoxetine in treating children and adolescents with depression are greater than the potential risk.

  • Feng ZHANG,Yunrui DI,Xiaoyuan XU
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    Objective To establish clinical pharmacists’ competency behavior questionnaire and confirm the validity of the competency model of clinical pharmacists. Methods On the basis of previous model research,clinical pharmacists’ behavior questionnaire combining the Likert scaling and literature retrieval method was established,and the competency model was verified by method of exploring factor analysis and "construct validity” and confirmatory factor analysis. Results Questionnaire included 47 characteristic projects and ten basic information projects.Exploratory factor analysis extracted 5 factors,whose content was in accordance with the model of competency characteristics.Cronbach 's alpha coefficients of each factor project were (0.510-0.961).Discrimination validity of the behavior questionnaire was good.T-test results showed good statistical difference between the outstanding group and the normal group,and the empirical validity of the model was better.Confirmatory factor analysis of structural equation model was acceptable,and the CIF was 0.825. Conclusion The competency model is valid and can distinguish clinical pharmacists with excellent performance.

  • Bijun LYU,Fenghua LIANG,Lu TAN,Wenying CHEN
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    Objective To discuss the contribution of clinical pharmacists in anti-infection treatment of a patient with multiple organ dysfunction syndrome (MODS) undergoing continuous renal replacement therapy (CRRT). Methods Pharmacists participated in the anti-infection treatment of a MODS patient undergoing CRRT.Pharmacists assisted physicians in optimizing the therapeutic regimen based on treatment guidelines and relative information. Results Physicians accepted the advice of pharmacists after comprehensive evaluation.Ten days later,the patient recovered from shock,as the infection indexes were improved significantly.He then moved back to the general ward. Conclusion Pharmacists should positively participate in clinical treatment with physicians,in order to play a critical role in ensuring the safety and efficacy of the medication.

  • Wenxi WANG,Sanlan WU,Chen CHEN
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    Objective To investigate the adverse drug reactions (ADRs) induced by escitalopram and precautions. Methods Wanfang,CNKI,Pubmed databases were searched to retrieve information about escitalopram adverse reactions reported in the literature,focusing on analysis of adverse reactions in patients with age,sex,clinical manifestations,involved systems, etc. Results Totally,31 references were collected,and a total of 31 cases included in the review analysis.The adverse reaction rate was equivalent between the male and the female.The adverse reaction occurred a few hours to 6 months after medication,and it involved several organ systems,including the nervous system,circulatory system,endocrine system,alimentary system,urinary system,kinetic system,etc. Conclusion Escitalopram should be used according to the doctor's advice,and its amount should not be arbitrarily added.Regular monitoring of adverse reactions should be performed to ensure rational use of the drug.

  • Xiaodan SU,Song FANG,Xudong FU
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    Objective To study and analyze the current situation of patient medication guide in foreign countries,aiming to provide references for the preparation of patient medication guide in China. Methods The current situation of patient medication guide by consulting literatures was mastered.In addition,the design concept of patient medication guide in foreign countries was summarized,the existing problems were analyzed,and the need for improvement was discussed. Results America,Australia,European countries and some Asian countries have developed a mature patient medication guide system under the supervision of the government departments.Patient medication information overseas takes patients' health literacy into consideration.It employs the concept of information design,focuses on risks and adverse reactions of drugs,and tells patients how to communicate with doctors and pharmacists.At the same time,it has some problems such as improper content and presentation,excessive emphasis on medication risk,not satisfying drug information demand of patients,as well as a lack of medication information for special groups such as the elderly. Conclusion The design,management and practice of patient medication guide in foreign countries set a good example for us.