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  • 01 September 2020 Volume 39 Issue 9
      

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  • Qiuchen CHENG,Wen QIN,Lang ZHUO,Yongzhong ZHAO,Liwen FAN,Wensi LIN,Ruibiao LIU
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    Objective To compare the anti-fibrosis effect of total flavone of Litchi Chinensis Sonn.(TFL) on perchlormethane-induced and bild duct ligation (BDL) hepatic fibrosis model of rats. Methods Totally 40 male rats were randomly divided into five groups,namely normal control group,carbon tetrachloride (CCl4) model control group,CCl4+TFL group,BDL model control group,BDL+TFL group,with eight rats in each group.CCl4 rats model was intragastric established by 40% CCl4 twice a week.BDL rat model was established by double bile duct ligation.CCl4+TFL group and BDL+TFL group were given TFL (300 mg·kg-1·d-1),normal control group,CCl4 group and BDL group were given 0.9% sodium chloride solution (300 mg·kg-1·d-1).Serum alkaline phosphatase (ALP),alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (T-BiL) in the rats were detected.The liver tissues were stained by HE and Sirius red.Expressions of α-smooth muscle actin(α-SMA) and Collagen Ⅰ in liver tissues were assessed by immunohistochemical staining.And the expression of α-SMA,nuclear factor-kappa B (NF-κB) p65,and cyclo-oxygenase 2(COX-2) in the liver tissues were determined by Western blotting. Results The effect of TFL in reducing the AST index in the CCl4 model was better than that in the BDL model (P<0.05).The BDL model was superior in reducing the T-BiL,spleen index,and α-SMA protein expression (P<0.05).Both models significantly reduced the percent of liver collagen area,the serum of ALT,ALP,and the expression of NF-κBp65 and COX-2 protein in rat liver (P<0.05). Conclusion TFL has efficacy of anti-fibrosis,improving the liver function of the rats in CCl4 and BDL liver fibrosis models.It is mainly anti-fibrotic and anti-inflammatory in CCl4 model,and reduce jaundice and anti-inflammatory in BDL model.Its mechanism may be related with TFL inhibit expression of inflammatory factors NF-κB p65 and COX-2.

  • Jiao LI,Shuiping OU,Jianyong ZHANG,Yongai XIONG,Sen WANG
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    Objective To predict the underlying mechanism of rutaecarpine in the treatment of cardiovascular disease (CVD) by reverse molecular docking and network pharmacological technology. Methods First, the drug-likeness (DL) of rutaecarpine was evaluated by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Second, the potential targets of rutaecarpine were predicted by reverse molecular docking with PharmMapper server and the main diseases related to rutaecarpine were obtained by Comparative Toxicogenomics Database (CTD). Then, the compound-target-cardiovascular disease network was built using cytoscape 3.60. After protein-protein interaction analysis and molecular docking verification, Biological Information Annotation Databases (DAVID) was used to analyze the enrichment pathways of anti-cardiovascular targets. Results The predictive analysis showed that HMOX1, F2, ALB, REN and CASP3 may be the key targets of rutaecarpine, and they participate in the regulation of VEGF, MAPK, HIF-1 and other signaling pathways. Conclusion Rutaecarpine is a potential drug candidate for the treatment of cardiovascular diseases, it can exert cardiovascular protection through a multi-target, multi-channel synergistic mechanism.

  • Shujuan ZHA,Jixi YAN
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    Objective To investigate the effect of pentoxifylline (PTX) on mesenchymal stem cells (MSCs) in the repair of glomerular endothelial cell injury in diabetic nephropathy mice. Methods MSCs and glomerular endothelial cells were cultured in vitro.The glomerular endothelial cell injury model was constructed by high glucose,and Transwell was used to complete co-culture of injured endothelial cells and MSCs cells.The experiment was divided into 6 groups: normal control group,injury group,MSCs group,MSCs+0.1 mmol·L-1 PTX group,MSCs+0.3 mmol·L-1 PTX group and MSCs+1 mmol·L-1 PTX group.MTT assay was used to detect the proliferation of endothelial cells in each group; flow cytometry was used to test the apoptosis rate of endothelial cells.Finally,the expressions of endothelin (ET),von willebrand factor (vWF) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blotting. Results Compared to the normal control group,the cell proliferation ability of the injured group decreased significantly,the rate of apoptosis increased,and the expression level of the injury markers of endothelial cell increased significantly.Compared to the injury group,the proliferation ability of cells in MSCs group and MSCs groups treated with different concentrations of PTX enhanced,apoptosis rate and the expression level of the injury markers were decreased.Compared with the MSCs group,the cell proliferation ability of MSCs + PTX group enhanced,apoptosis rate and the expression level of the injury markers were decreased. Conclusion PTX have promoting effect of MSCs on the proliferation of glomerular endothelial cells in diabetic nephropathy rat,the inhibitory effect of apoptosis and the repair effect of the cell injury.Furthermore,in low dose range,the promotional effect of PTX shows a concentration dependence.

  • Jiang LOU,Gang WANG,Qingyu LI,Ling CHEN,Lin WANG,Cheng YI,Wei YAN
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    Objective To investigate the mode of pre-prescription review in order to improve safe and rational use of drugs. Methods The rules of pre-prescription review were formulated by the rational drug use system.The data of outpatient and emergency prescriptions,and inpatient medical orders were collected.The impacts of system review combined with or without manual review on the rational drugs use were compared. Results Compared with the system review mode,the combined mode can reduced the false positive rate of outpatient and emergency prescriptions and inpatient medical orders by 6.27%and 8.40%respectively. Conclusion The combined mode of system and manual review of pre-prescription review system is a reasonable mode,which regulates the doctor's prescription behavior effectively, improves the rational drugs use,and raises the quality of prescriptions.

  • Hui CHEN,Shihui WANG,Dongsu ZHANG,Rui ZHAO,Xiaojia YU,Ye SU,Lihong LIU
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    Objective To evaluate the value of pharmaceutical care through the pre-prescription review provided by pharmacists. Methods One-week’s prescriptions from one year before and three years after the reform of the pre-audit process in a Third-Level medical institution in Beijing were selected,and the prescription was evaluated with the same auditing standard.The difference of prescription problems before and after the reform of pre-audit process,were compared to evaluate the value of pharmaceutical care. Results Compared with the pre-reform period,the number of drugs per capita decreased from 3.97 to 3.04; per capita drug cost decreased from 380.02 yuan to 337.65 yuan.The percentage of unqualified orders fell from 12.21% to 0.36%.among which drug use for no indication decreased from 6.18% to 0.03%; unsuitable usage and dosage decreased from 4.61% to 0.32%; unsuitable combination of drugs decreased from 1.24% to 0.01%; and contraindications decreased from 0.18%to 0.00%. Conclusion Pharmacists can reduce the risk of drug use and the average drug cost for each patient by providing pre-prescription audit services.

  • Qinghua ZHANG,Rui JIN,Kun WANG,Dan YAN
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    Objective To investigate the satisfaction and suggestions of outpatient doctors with the pre-prescription review system,and to promote its use to ensure safe and rational drug use. Methods An online questionnaire was administered to the outpatient doctors who used the pre-prescription review system software in a third grade class-A hospital in Beijing.The questionnaire was released with a mobile phone QR code,and the collected data were statistically analyzed by Likert scale method. Results The overall level of satisfaction of the 108 respondents with the pre-prescription review system software was 3.81 points (the corresponding rate was 76.2%,close to satisfaction).To the responded clinical pharmacists,the overall satisfaction with the pre-prescription review system scored 4.08 points (the corresponding rate was 81.6%,satisfaction).Analysis of doctors with different medical specialties found that the satisfaction score was significantly lower among the respondents from internal medicine departments than those among those from the surgery departments (3.67±0.92 points vs 4.19±0.75 points).The 48.15%of the responded physicians may have been complained by patients due to the delay of the software,and the satisfaction score of these physicians was significantly lower than whom without patient complaint experience (3.48±0.90 points).The most frequent prompts that the respondents complained were as follows: "The drug is recommended in the guidelines,but it is the off-label use","the usage and dosage",and "selection of drug preparation solvent ".The respondents expressed their concerns on the accuracy and efficiency of the software.In addition,the pre-prescription review rules,and the diagnostic databases of the software were considered to be imperfect and incomplete,which were expected to be further improved. Conclusion The effect of pre-prescription review can be effectively promoted by conducting the questionnaire survey of outpatient doctors.

  • Guangjie WU,Yu LIU,Yunzhou CHEN,Zhen WANG,Xuepeng GONG,Dong LIU,Juan LI
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    Objective To introduce the pre-prescription review mode in a hospital,to evaluate the effect of the work,and to provide reference for rational drug use. Methods Data of pre-prescription review system from May 2019 to August 2019 were analyzed retrospectively to compare the amount of irrational prescriptions with different problems,and find out the causes. Results From May 2019 to August 2019,the amount of prescription problems in drug delivery route,pediatric drug use,drug concentration,drug compatibility,drug contraindications,pregnancy drug use,interaction,adult drug use,and drug use in restricted genders,of outpatient prescriptions showed a decreasing trend.The rate of qualified prescriptions increased.The number of problems in the over-day dosage and dosage range showed an overall trend of increase.Meanwhile the number of over-day dosage problems decreased in August. Conclusion Pre-prescription review has played a promoting role in improving rational drug use in the hospital.Pharmacists should continuously maintain the rule base,strengthen communication with doctors,and establish a working mode of pre-prescription review based on evidence.

  • Kaishan WU,Junyan WU,Zhihua ZHENG,Kaifeng QIU
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    The off-label use is inevitable in hospital.The review of off-label prescription ensures the safety of patients,avoids the risk of medical institutions and medical staffs,and reduces medical disputes.Currently,the method of evaluating off-label use and reviewing that prescription are lacking in China.This aim of this article was to introduce key element and methods of the previously off-label reports and our team's practical experience.It will provide a reference for pharmacists to review the off-label drug prescription,so as to manage medical institutions' off-label drug and improve the level of reasonable drug use.

  • Jie CHEN,Xiaojiao GONG,Pan CHEN,Xiao CHEN,Jing XU
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    Audit of pregnancy medication prescription need to consider maternal and fetal,which has its own particularity. Audit of pregnancy medication prescription aims to ensure the safety of pregnant women and fetal medicine.Therefore,the prescription of pregnancy patients was audited by pharmacist,the safety of the drug should be focused.The principle of women during pregnancy drugs was performed,the contraindications of the drug was strictly carried out, guidelines recommend the rationality of drug use and off-label use management was executed.In this article,the aimed to the prescription of pregnancy patients audit ideas and methods,The program and key points of pregnancy drugs prescription was audited,the ability of pharmacist prescription audit should be further improved.

  • Ronggui GUAN,Yining XU,Shu LIU,Tao LIU
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    Objective To sort out the key points of antineoplastic agent prescriptions audit,and to promote safe and rational use of these drugs. Methods Based on the authors’ work experience,relevant documents and clinic evidences,the key points in the works of antineoplastic agent prescription audits were sorted out and discussed. Results The audits of antineoplastic agent prescriptions involve three aspects of legality,standardization and suitability.In the suitability audits,the following situations should be emphasized,such as whether the indication is appropriate,whether the selected regimen or drug is appropriate,whether the drug dosage form or route of administration is appropriate,whether the dosage is appropriate,whether the solvent is suitable,whether the pretreatment is appropriate,whether the combination is appropriate,whether the order of administration is appropriate,etc. Conclusion The audits of antineoplastic agent prescriptions involve a wide range of situations,and the medical evidence updates quickly.Pharmacists should continuously improve their professional skills.Based on the latest medical evidence for drug uses and the actual drug use situations of the hospital,pharmacists should establish and maintain the prescription audit rules of their own hospitals.

  • Jing LI,Huizhu SONG,Xiao ZHOU,Lin YU,Hongyan MA
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    Objective To promote the pre-prescription review and proper clinical use of β-lactamase inhibitor compound preparations. Methods A “self-maintenance rule base” was established with the help of the pre-prescription review system (MIND system),and fine set the prescription authority,etiology inspection,usage and dosage,combined medication,treatment course,etc.of the β-lactamase inhibitor compound preparation.The utilization rate,consultation rate,course of treatment of the drugs before and after the management were calculated,the qualified rate of prescriptions was evaluated by sampling,and the effect of fine setting was evaluated. Results After fine management,the utilization rate of β-lactamase inhibitor compound preparation in the hospital decreased from 8.25%to 5.82%,the consultation rate increased from 11.43%to 77.40%.The average therapy duration was shortened,and the unqualified rate of prescriptions decreased from 38.33%to 4.76%.The problems such as indications,usage and dosage,combined medication and course of treatment were significantly improved. Conclusion The fine setting of the rules for β-lactamase inhibitor compound preparation could effectively promote the development of pre-prescription review and promote the rational use of drugs.

  • Xiaoyu YANG,Han LUO,Jianyong SHENG,Jiangling WAN,Xiangliang YANG
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    Oral route is one of the most convenient,safe ways for drug delivery, which has high patient compliance.However,successful and efficient oral delivery of most approved drugs still faces formidable challenges,due to the gastrointestinal multiple barriers to drug absorption and the low solubility,stability or permeability of the drugs.Nano drug delivery systems have been proved to improve the oral bioavailability of encapsulated drugs by overcoming the multiple absorption barriers.Surface modification of nano drug delivery system with proper ligands can further enhance its efficiency of oral delivery.In this publication,the current status of ligand modified nanoparticle formulation for oral drug delivery was reviewed,and the characteristics of small-molecule ligand and peptide/protein ligand modified nano-carriers were summarized.Furthermore,the strategies of ligand modification of nano-carriers for oral drug delivery in future studies were prospected.

  • Jing AN,Jiangling WAN,Xiangliang YANG,Zifu LI
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    Enzyme responsive nanomedicine is a kind of nano drug delivery system that changes its physical and chemical properties by endogenous enzyme.It can control the delivery and release of lipophilic drugs,proteins and genes,upgrade their water solubility,reduce their toxic and side effects,and increase their circulation time.Enzyme responsive nanomedicine can be applied in chemotherapy,gene therapy,photothermal therapy and photodynamic therapy for cancer treatment.This unique stimulus-response function is widely used in drug delivery,disease diagnosis and biomedical imaging.Herein,research progress of enzyme responsive nanomedicine is summarized,and the challenges and future development of enzyme responsive nanomedicine are discussed.

  • Haowen ZENG,Xiangliang YANG,Zifu LI
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    With the rapid development of nanotechnology,novel nanoprobes have revealed the evolution of tumor mechano-microenvironment from tissue,cell and molecule levels; and some new nanooperators have achieved tumor killing or improved the efficacy of cancer therapy by intervening tumor mechano-microenvironment or cancer cell mechanics.The application of nanotechnology in tumor mechanobiology has fostered a new research hotspot,namely mechano-nanooncology.In this review, the authors attempt to define the term mechano-nanooncology and summarize the latest advances in leveraging mechano-nanoprobes and mechano-nanooperators for the study of tumor mechanobiology.Finally,the authors discuss current challenges of mechano-nanooncology and look forward to its future development.

  • Dongsheng MOU,Yuan LIAO,Xiaoshun ZHOU,Jiangling WAN,Xiangliang YANG
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    Recently,pharmaceutical enterprises paid more and more attention to develop nanocrystal medicine with high value by taking advantage of nanotechnology.For nanocrystal medicine,controllable preparation process of nanocrystal and final product with advantages of pharmaceutics are key factors which influence the success of products.In this paper,information related to nanocrystal medicines including preparation process and characterization method are reviewed.The advantages of typical products are discussed and the future applications are prospected.

  • Jiajing SUN,Jiangling WAN,Xiangliang YANG,Zifu LI
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    Heparin is a kind of water-soluble natural polysaccharide,with excellent biocompatibility and degradability, as well as anticoagulant,anti-angiogenesis and anti-tumor metastasis activities.Heparin can also be utilized for surface modification of nanomedicine,thereby increasing aqueous solubility of chemotherapeutic agents,reducing toxicity of drugs,and achieving prolonged blood circulation.Besides,it can be used as the backbone of nano drug delivery systems to achieve efficient delivery of hydrophobic drugs,proteins and genes.Therefore,heparin-based nanomedicine can be widely applied for tumor diagnosis,photodynamic therapy,gene therapy and combination therapies,which holds enormous potential for the treatment of malignant solid tumors and highly metastatic tumors.This paper reviews the most recent research progress of heparin-based nanomedicine and looks forward to its future development.

  • Anping YANG,Siying GU,Yijun LIANG,Zhuo DU
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    Objective To investigate the prescription and process of astaxanthin liposome by ethanol injection method. Methods Astaxanthin liposome was prepared by ethanol injection.Encapsulation efficiency was taken as index to screen the prescription and process of astaxanthin liposome by single factor test and orthogonal test.The characterization of astaxanthin liposome was measured. Results The optimal prescription and process were as followed:the ratio of lipids to astaxanthin was 40:1; the ratio of phospholipid to cholesterol was 20:1; pH of hydration medium were 7.0. The temperature was 60 ℃. Average encapsulation efficiency was (35.28±0.93)% and mean particle size was about 143.2 nm. Conclusion The process of astaxanthin liposome prepared by ethanol injection method is simple, and suitable for industrial manufacture.

  • Qiuju YU,Xiaoli WANG
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    Objective To study the effect of pH value on the physicochemical properties and in-vitro percutaneous permeability of ketoprofen (KP) and to provide experimental basis for the preparation of microemulsion gel. Methods HPLC method was used to determine the equilibrium solubility (S),apparent oil water partition coefficient (P),steady state permeability rate (Js),and permeability coefficient (Ps) of KP in water and phosphate buffer saline (PBS) when pH values was 5.0,6.8,7.4,8.0,and 9.0,respectively.Multiple linear regression was used to establish the correlation between the in vitro transdermal parameters,pH,S and P. Results At 32 ℃,KP is insoluble in water.In the PBS of pH 7.4,KP showed largest equilibrium solubility,Js and Ps.The multivariate linear regression results showed that pH,S,P and Js are linearly correlated.The regression equation was: Js=-0.268 pH +1.099S-0.141P+92.121. Conclusion By adjusting the pH,the S,P,and Js of the KP can be improved.According to the results,the KP can obtain higher solubility,lipid solubility,and skin permeability in a PBS solution with a pH of 7.4.

  • Hengyi YU,Xiuhua REN,Aihua DU,Dong LIU,Kaifu WANG,Qian CHEN
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    In order to ensure the quality of clinical trials,a sound and effective level-2 quality control (QC) system was established in our phase I clinical trial unit,according to the GCP requirements and the key points for on-site verification of drug clinical trial data issued by National Medical Products Administration of China.The QC personnel,QC type,QC stage,and QC content in the level-2 QC system were introduced in this paper,which covered the whole process of clinical trials,including preparation stage,subject screening stage,trail stage and end stage.With the implement of this system,key steps during the process of phase I clinical trial and bioequivalence (BE) test were under control objectively,timely,professionally,and effectively,which significantly improved the quality of clinical trials and protected the rights of subjects.