最新刊期
卷 33 ， 期 13 ， 2022
- 摘要：OBJECTIVE To discuss the difficulties in t he development of complex preparations and puts forward solutions ，in order to provide some reference for the development and preparation of complex preparations. METHODS Based on the development status of complex preparations ，the challenges faced by the development of complex preparations were analyzed ，and the countermeasures for the development of complex preparations were proposed. RESULTS & CONCLUSIONS The development of complex preparations required high quality of personnel ，and was limited by pharmaceutical excipients ，delivery devices and pharmaceutical equipment. The preparation process was complex ，there were many quality control parameters and patent barriers. Complex preparation development enterprises need to pay more attention to talents ，pharmaceutical excipients ，delivery devices and pharmaceutical equipment ，and clarify the impact of key technology on preparation production and quality characteristics ；in addition，they need to strengthen independent research and development ，crack the patent layout of original research enterprises and protect their own innovative achievements. Domestic complex preparation development enterprises can combine imitation and innovation to develop complex preparation products with independent brands to better meet the needs of patients.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To interpret the revision of the in dicators o f pharmaceutical administration in National Tertiary Public Hospitals Performance Evaluation Operational Manual （2022 edition）[hereinafter referred to as the Mannual（2022 edition）]，and to provide reference for the implementation of a new round of performance appraisal in tertiary public hospitals. METHODS The contents and revision details of the indicators of pharmaceutical administration in the Mannual（2022 edition）were described briefly，and the revised contents were interpreted and relevant suggestions were put forward. RESULTS & CONCLUSIONS The Manual（2022 edition）continued the scope of performance evaluation ，indicators’structure and sequence in the Manual（2020 edition），which focused on rational drug use and drug cost control. The Manual （2022 edition） placed more emphasis on strengthening the provision and use of essential medicines and selected drugs in the centralized drug procurement ，and further reducing the burden of medical costs in patients. It is suggested that tertiary public hospitals scientifically set indicators for the use of essential medicines ，selected drugs in the centralized drug procurement ，auxiliary drugs and antibacterial drugs in clinical departments，and improve relevant incentive mechanisms and performance assessment systems ；strengthen the interpretation of policies about essential medicines and drug centralized procurement ，as well as the training of rational drug use ；optimize in-hospital drug catalog and formulary ；formulate medication standards ，strengthen prescription review ，rational medication review and assessment ；establish and improve the drug use monitoring and evaluation and early warning system so as to standardize clinical drug use behavior by information technology ；strengthen the use of essential drugs and centrally purchase selected drugs on the basis of ensuring rationality ；control the unreasonable gradually reduce the increase in average drug costs.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To identify and evaluate the risk factors in the operation process of the vaccine supply chain ，clarify the importance of each process risk in the overall risk of the vaccine supply chain ，and provide reference for stakeholders in the vaccine supply chain to formulate risk management and control strategies. METHODS In the supply chain operation reference model，the risk factors existing in the operation of vaccine supply chain were identified ，and the vaccine supply chain risk evaluation index system was constructed. The best-worst method and entropy weight method were used to determine the subjective and objective weight of the index ，and the Lagrange multiplier method was used to solve the optimal combination weight value of the index. RESULTS & CONCLUSIONS A vaccine supply chain risk evaluation index system with 18 indexes was established. Only 67％ of the indexes reflected 85％ of the vaccine supply chain risk information. The construction of the system was reasonable. The results showed that the risk weight of production process was 0.607，which accounts for the highest weight in the overall risk of vaccine supply chain ，followed by procurement （0.234），distribution（0.102），planning（0.053）and return （0.004） process risk . When managing and controlling risks ，enterprises should attach great importance to the risk factors in vaccine production；at the same time ，enterprises should also focus on other risks such as unqualified materials for products ，mixed use of materials and so on.关键词：vaccine;supply chain;best-worst method;entropy weight method;combination weighting method;risk assessment
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发布时间：2022-11-09 - 摘要：OBJECTIVE To learn the common proto col deviation （PD）in the process of drug clinical trials and discuss the methods and precautions for preventing and reducing PD so as to provide reference for the standardization of drug clinical trials. METHODS According to Good Clinical Practice ，Notice on Issuing Guidelines for Planning and Reporting of Data Management and Statistical Analysis of Drug Clinical Trials ，Guidelines for Ethical Review of Drug Clinical Trials ，ICH E 3，ICH E 6（R2）and other regulations ，the PD reported in the relevant projects managed by the author from March 2017 to February 2022，as well as the PD found in the submission materials and project quality control ，were sorted out and statistically analyzed. RESULTS & CONCLUSIONS A total of 39 drug clinical trials were included ，and 212 subjects were selected. In all projects ，258 PDs were reported，including 28 major PD （accounting for 10.85％）and 230 ordinary PD （accounting for 89.15％）. The report of PD mainly included missed inspections/tests （93 reports，accounting for 36.05％），lack of visits （36 reports，accounting for 13.95％）， inspection/testing out-of-window （29 reports，accounting for 11.24％），dosage and usage of test drugs （28 reports，accounting for 10.85％），drug over-temperature/missing temperature （21 reports，accounting for 8.14％），etc. Avoiding and reducing the occurrence of PD requires the efforts of multiple parties ：the sponsor designs a reasonable protocol with appropriate interview rate and window period after listening to the opinions of multiple parties ；the investigators and clinical research coordinator should strengthen their own learning and training ，and be familiar with the protocol ，Good Clinical Practice and corresponding regulations；the compliance education of the subjects should be strengthened ；the institutional offices and ethics committees should conduct multi-angle and whole-process supervision and management when a drug clinical trial is approved ，in progress ，and jsyj- concluded，to ensure the safety rights and interests of the zdcxX0079） subjects and the quality of clinical trials. On this basis ，all parties should communicate effectively and timely ，report PD in time ，and conduct special studies on major PD that have com occurred and key links that are prone to PD.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To quantitatively evaluate the existing payment policies of diagnosis-related groups （DRGs）in China ， so as to provide reference for the formulation and improvement of policies. METHODS Totally 58 documents related to DRGs payment issued by the national and provincial medical security bureaus from 2017 to 2022 were processed by text mining method. PMC index evaluation model of DRGs payment policy was established. Nine typical DRGs payment policies were quantitatively evaluated and analyzed by 10 primary variables and 40 secondary variables. RESULTS Among the 9 policies，5 were excellent and 4 were acceptable. The average score of PMC index was 6.882. Generally ，there was still room for improvement because of the acceptable level. By comparing the two representative policies ，it was found that the main reasons was a lack of consideration in terms of supervision and management ，incentives and constraints when facing policy changes ，reason of the lower level of urban development. CONCLUSIONS Although DRGs payment policy in China is basically perfect ，there is still a lot of room for improvement in terms of extending the time limit of the policy ，summarizing and spreading the successful experience of pilot cities.关键词：diagnosis-related groups;payment policy;PMC index model;Quantitative evaluation
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发布时间：2022-11-09 - 摘要：OBJECTIVE To prep are Legumain enzyme and mitochondrial double-stage targeted harmine （HM） liposome （KA@HM-LPS）and preliminary evaluate its pharmaceutical properties ，in vitro antitumor effect and biocompatibility. METHODS Firstly，the preparation and homogenization methods of KA@HM-LPS was screened ，and prepared liposomes were characterized. Secondly，the serum stability ，in vitro release rate ，hemolysis percentage of KA@HM-LPS and cell survival rate under KA@BLPS were determines respectively. Finally ，the cell surivival rate ，mitochondrial targeting and inhibitory effects on cell migration and invasion of KA@HM-LPS were determined. RESULTS KA@HM-LPS was prepared by the thin-film dispersion method ，with encapsulation efficiency of （90.50 ± 0.62）％ . The extrusion moulding method was selected as homogenization method of KA@HM-LPS. The particle size ，polydispersity index ，and Zeta potential of KA@HM-LPS were （211.40±11.67）nm，0.316± 0.014 and（－14.20±0.49）mV，respectively. In 37 ℃，10％ FBS，the particle size of KA@HM-LPS kept stable after 12 h. In vitro release curve of KA@HM-LPS in 20％ plasma conformed to Weibull distribution and had the property of sustained release. When HM concentration was 160 μg/mL，the hemolysis percentage of KA@HM-LPS was （4.23±0.19）％，which was much lower than that of free HM ，with safety. When the mass concentration of KA@BLPS reaches 400 μg/mL，the survival rate of LO 2 cells was （94.40 ± 6.12）％ ，and the biocompatibility was good. Cell test results in vitro showed that ，inhibitory effect of KA@HM-LPS on liver cancer cells with overexpression of Legumain enzyme （LGMN -SK-Hep-1） was significantly higher than that of normal liver cancer cells SK-Hep- 1； compared with SK-Hep-1，LGMN +-SK-Hep-1 cells had a higher uptake efficiency of the liposome ；KA@HM-LPS could significantly inhibit the migration and invasion of LGMN +- SK-Hep-1 cells. CONCLUSIONS KA@HM-LPS is prepared successfully ，which can effectively inhibit the migration and invasion of liver cancer cells with Legumain enzyme overexpression ，and improve the blood compatibility of HM.关键词：harmine;Mitochondria;Legumain enzyme;liposome
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发布时间：2022-11-09 - 摘要：OBJECTIVE To explore t he protective mechanism of Yangxin dingji capsules on the cardiomyocytes of diabetic cardiomyopathy（DCM）model golden hamsters. METHODS In this study ，golden hamsters were divided into control group （n＝ 10，no modeling ，no drug administration ），model group （n＝9，modeling，no drug administration ），TCM high-dose group [ n＝8， modeling，Yangxin dingji capsules 2 g/（kg·d）]，TCM low-dose group [ n＝8，modeling，Yangxin dingji capsules 1 g/（kg·d）] and empagliflozin group [ n＝9，positive control ，modeling，10 mg/（kg·d）]. All the golden hamsters were gavaged continuously for 8 weeks. The general conditions of golden hamsters were observed during the experiment. Blood glucose ，total cholesterol （TC）and creatine kinase MB （CK-MB），ejection fraction （EF），fractional shortening （FS），interleukin 1β（IL-1β）and transforming growth factor β1（TGF-β1）were detected ；the histopathological changes of myocardium were observed. mRNA and protein expression of nucleotide-binding oligomerization domain-like receptor protein 3（NLRP3），caspase-1，aspirin D （GSDMD），nuclear factor κB （NF-κB）and IL- 1β were detected and observed；DNA damage in myocardial was detected. RESULTS Compared with control group，the blood glucose ，TC，CK-MB，serum IL- 1β，TGF-β1 levels，the mRNA expressions and positive protein expression of NLRP 3，caspase-1，GSDMD，NF-κ B and IL-1 β and protein expression of GSDMD in golden hamsters were significantly increased in model group （P＜0.05 or P＜0.01） EF and FS were significantly decreased （P＜0.01）；the fibers of myocardial cells was disordered ， and the blue-stained collagen fibers between the myocardium increased ； DNA damaged positive cells in myocardial tiss ue of gold hamsters increased significantly. Compared with model group，the above indexes of administration groups were reversed to varying degrees ；the gap of myocardial cells were clear ，and the fibers disorder was improved ；the DNA damaged positive cells in the myocardial tissue were reduced to varying degrees. CONCLUSIONS Yangxin dingji capsule can inhibit the cardiomyocyte pyroptosis and relieve the inflammatory injury of DCM in DCM model golden hamsters by regulating the NLRP 3/caspase-1/GSDMD signaling pathway ，so as to protect the cardiomyocytes.关键词：Yangxin dingji capsule;diabetic cardiomyopat hy;NLRP3/caspase-1/GSDMD signaling pathway;cardiomyocyte
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发布时间：2022-11-09 - 摘要：OBJECTIVE To investigate the effect and mechanism of Poria cocos polysaccharides on the regulation of blood glucose in type 2 diabetes mellitus （T2DM）model rats by phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）/forked box transcription factor O 1（FoxO1）pathway. METHODS SD rats were randomly divided into blank control group （no modeling ，no administration），model group （modeling，no administration ），metformin group （modeling，200 mg/kg）and P. cocos polysaccharide low-dose，medium-dose and high-dose groups （modeling，100，200，400 mg/kg），8 in each group. Except for blank control group ， other groups were given high fat diet combined with streptozotocin to construct the model of T 2DM rats. At the same time ， administration groups were given relevant dose of medicine intragastrically ，and blank control group and model group were given constant volume of water intragastrically ，once a day ，for consecutive 42 days. During the experiment ，general condition and bodyweight of rats were observed every day ；fasting blood glucose （FBG）of rats were collected ，and oral glucose tolerance test were conducted and area under curve （AUC）was calculated the day before last administration. After last medication ，the heart ，liver， kidney organ index were calculated ；the levels of HbA 1c，TC，TG，MDA，SOD，GSH-Px and hepatic glycogen content were detected. HE staining was used to observe the pathological changes of liver and pancreatic tissue ，and the pathological grade score was calculated. Western blot assay was used to detect the protein expressions of p-PI 3K，p-Akt，p-FoxO1， PEPCK and G 6Pase in liver tissues. RESULTS Compared with blank control group ，the rats of model group suffered cc1965@163.com from polydipsia ，polyphagia and polyuria ；the body weight ， the levels of SOD and GSH-Px ，the protein expressions of p-PI 3K，p-Akt and p-FoxO 1 were significantly decreased （P＜0.05）；liver and kidney organ index ，blood glucose level at 0，0.5 and 2 hours after intragastric administration of glucose solution ，AUC， FBG，HbA1c，serum levels of MDA ，TC，TG and hepatic glycogen content ，liver and pancreatic pathological grade score ，the protein expressions of PEPCK and G 6Pase were all increased significantly （P＜0.05）. Compared with model group ，the general condition of rats in P. cocos polysaccharide groups were all improved ，and all of above indicators had been reversed to varying degrees. CONCLUSIONS P. cocos polysaccharide can downregulate protein expressions of PEPCK and G 6Pase which are key enzymes of gluconeogenesis ，inhibit hepatic gluconeogenesis ，effectively decrease blood glucose levels and regulate glucolipid metabolism in T 2DM model rats by weakening oxidative stress and upregulating PI 3K/Akt/FoxO1 pathway.关键词：Poria cocos polysaccharides;Type 2 diabetes mellitus;Oxidative stress;PI3K/Akt/FoxO1 pathway;gluconeogenesis
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发布时间：2022-11-09 - 摘要：OBJECTIVE To study the vasorelaxant effects and mechanism of polyphenol compound 2，4′，5′-trihydroxy-5，2′- dibromo-diphenyl-methanone（LM49）on isolated aortic rings of rats. METHODS Thoracic aortic vascular rings of rats were collected. Using the diastolic rate as index ， the effects of different concentrations of LM 49 on endothelium-intact and endothelium-denuded aortic rings pre-contracted by norepinephrine （NE，1×10－6 mol/L）or KCl （60 mmol/L）were investigated. After pre-culturing vascular rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester （L-NAME，0.1 mmol/L） and cyclooxygenase inhibitor indomethacin （1×10－5 mol/L），as well as pre-culturing vascular rings by 4 potassium channel blockers [BaCl 2（0.1 mmol/L），tetraethylammonium（TEA，5 mmol/L），4-aminopyridine（4-AP，0.1 mmol/L）and glibenclamide （1×10－5 mol/L）]，the vasorelaxant effect of different concentrations of LM 49 on the vascular rings were investigated by using the same method. With the percentage of vasoconstriction as the index ，using KCl （60 mmol/L），NE（1×10－6 mol/L），calcium channel blocker verapamil （1×10－6 mol/L）and sarcoplasmic Δ 基金项目 重大新药创制国家科技重大专项 （No.2018ZX097- reticulum Ca 2 +-adenosine triphosphate （ATP） enzyme pump inhibitor thacarotene （TG，1×10－6 mol/L）to induce the release of calcium in vascular rings in the absence of calcium. CaCl was added cumulatively ，and the effect of LM 49 on the cxyw06，vasoconstriction caused by calcium influx induced by CaCl 2 was investigated. RESULTS 3×10－6，5×10－6，1×10－5 mol/L LM49 had a significant relaxation effect on NE and KCl precontracted vascular rings （P＜0.01）； whether the endothelium was removed or not had no significant effect on the vasodilation of LM 49（P＞0.05）. After L-NAME ，indomethacin， TEA and 4-AP was pre-incubated ，different concentrations of LM 49 had no significant effects on aortic rings precontracted by NE （P＞0.05）. Glibenclamide and BaCl 2 could inhibit the vasorelaxant effects of LM 49 on aortic rings precontracted by NE （P＜0.01）. In the absence of calcium ，LM49 could inhibit the contraction caused by calcium influx induced by accumulated CaCl 2 after pre-incubation with KCl ，NE，verapamil and TG （P＜0.01）. CONCLUSIONS LM49 evokes significant relaxation of isolated aortic vascular rings without endothelium dependence ；the mechanism of which is inducing ATP-sensitive potassium channel ， inward rectifier potassium channel open and restraining extracellular Ca 2 + influx via voltage-gated calcium channel ， receptor-operated calcium channel and store-operated calcium channel.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To prepare and evalu ate doxorubicin-loaded red blood cell membrane chitosan-targeted nanoparticles of targeting tumor cell folate acid （FA）receptor（FA-RBC-DOX-CS-NPs）. METHODS Doxorubicin-loaded chitosan nanoparticles （DOX-CS-NPs） were prepared by ion cross-linking method. FA and amino polyethylene glycol phospholithin （NH2- PEG2000-DSPE）were covalently linked to modify the red blood cell membrane to construct FA-RBC-DOX-CS-NPS. FA-RBC- DOX-CS-NPs were characterized and investigated on in vitro drug release characteristics ，antitumor activity and endocytosis ability （investigation with human breast cancer MCF- 7 cells）. RESULTS Average particle size of FA-RBC-DOX-CS-NPs was （254.200± 2.651）nm，and polydispersity index was 0.199±0.031；Zeta potential was （－10.100±0.213）mV. FA-RBC-DOX-CS-NPs released fast in the tumor microenvironment （pH6.5）. Cellular experiments showed that ，the nanoparticles could inhibit the activity of MCF- 7 cell proliferation and improve the efficiency of endocytosis. CONCLUSIONS FA-RBC-DOX-CS-NPs are prepared successfully. The nanoparticles have good tumor cell targeting and endocytosis ability ，and can realize the enrichment of drugs in tumor cells.关键词：red blood cell membrane;Nanoparticles;folic acid receptor;targeted drug delivery system;Anti-tumor
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发布时间：2022-11-09 - 摘要：OBJECTIVE To establish the method for the content determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Shexiang zhuanggu plaster ，and to evaluate the quality of 222 batches of Shexiang zhuanggu plaster from 41 manufacturers. METHODS HPLC method was established. The determination was performed on Shimadzu Shim-pack GIS-C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid （3∶97，V/V）at the flow rate of 0.9 mL/min. The column temperature was set at 30 ℃，the detection wavelength was 210 nm，the sample size was 10 μL. Taking the content data of 222 batches of samples as index ，the cluster heatmap was drawn by Hiplot biomedical data visualization and analysis platform. RESULTS The results of the methodological investigation were in line with the requirements of the general principles stated in 2020 edition of Chinese Pharmacopoeia （part Ⅳ ）. The total contents of ephedrine hydrochloride and pseudoephedrine hydrochloride in 222 batches of samples from 41 manufacturers were 0.646-6.325 μg/cm2. Results of cluster heatmap analysis showed that these samples of 41 manufacturers could be divided into 3 categories. The contents of components in samples from different manufacturers varied greatly ，and the contents of components in different batches of samples from the same manufacturers also varied greatly. If the proposed limit of this product was that the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride per 1 cm2 would not be less than 1.00 μg，23 of the 222 batches of samples were unqualified. CONCLUSIONS The established method for the content determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Shexiang zhuanggu plaster is accurate and precise ，and can be used for the quality control. Some manufacturers should pay attention to optimizing production process and strengthening quality control.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To optimize the extraction technology fo r phenylethanol glycosides from Cistanche deserticola by natural deep eutectic solvents （NADESs），and to provide reference for the development and utilization of C. deserticola . METHODS The optimal NADESs was selected using total extraction efficiency of echinacoside ，acteoside and isoacteoside as indexes. Based on single factor test ，response surface methodology was used to select the optimal NADESs molar ratio ，the optimal NADESs water content ，the optimal liquid-solid ratio ；and the results were optimized by genetic algorithm . Using vitamin C （VC） as positive control ，the extraction effects of NADESs and traditional solvent （50％ methanol）were compared in respects of extraction efficiency and antioxidant activities. RESULTS The optimal extraction solution was NADES- 11 composed of 1， 4-butanediol and malonic acid. The optimal extraction technology was as follows as the molar ratio of 1，4-butanediol-malonic acid was 1 ∶ 2.5，water content of NADES- 11 was 18％，liquid-solid ratio was 30 mL/g，extraction time was 30 min and extraction temperature was 30 ℃. The extraction efficiency of NADES- 11 was significantly higher than that of 50％ methanol（P＜0.05）. IC 50 values of NADES- 11 extract（261.17 and 744.34 µg/mL）to 1，1-diphenyl-2-trinitrophenylhydrazine radical and hydroxyl radical were all lower than those of 50％ methanol extract （420.97 and 1 175.12 μg/mL）. Ascorbic acid equivalent antioxidant capacity of Δ 基金项目 内蒙古自治区科技创新引导项目（No.00120209）；内 NADES-11 extract（17.19 and 360.80 mg VC/g ）was higher 蒙古自治区自然科学基金资助项目 （No.2021MS08011）；内蒙古自治 than that of 50％ methanol extract （10.67 and 228.54 mg 区医疗卫生科技计划项目（No.202201367）；包头医学院“花蕾计划”项 VC/g）. CONCLUSIONS The optimized extraction process of 目（No.HL2021046） phenylethanol glycosides from C. deserticola using NADESs is ＊第一作者 硕士研究生。研究方向：中蒙药药效成分。E-mail： environmental，stable and feasible. dongjiani369@126.com
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发布时间：2022-11-09 - 摘要：OBJECTIVE To study the effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in rats with bone cancer pain. METHODS After treatment via intrathecal tube ，the rats were randomly divided into sham operation group ，model group ，resveratrol low-dose ，medium-dose and high-dose groups （0.25，1，2 mg/kg），with 8 rats in each group. Except for sham operation group ，other groups were given Walker 256 breast cancer cell suspension on the right hind limb tibia to induce bone cancer pain model. After 12 days of modeling ，intrathecal administration was performed in resveratrol groups. The model group and sham operation group received the same volume of dimethyl sulfoxide ，10 μL，once a day ，for 5 days. The paw withdrawal mechanical threshold （PWMT）and paw withdrawal thermal latency （PWTL）were measured at 3 d，5 d after administration. The serum levels of tumor necrosis factor α（TNF-α），interleukin 6（IL-6），IL-1β and chemokine ligand 2 （CCL2）were determined after last medication ，and the protein expressions of RANK ，RANK-L and OPG in tibia were also determined. RESULTS Compared with sham operation group ，PWMT and PWTL were significantly decreased in the model group 12 days after operation （P＜0.05）. Compared with model group ，PWMT and PWTL were significantly increased in resveratrol medium-dose and high-dose groups at 3 d and 5 d after administration （P＜0.05）. Compared with model group ，the levels of TNF-α，IL-6，IL-1β and CCL2 in serum were significantly decreased in resveratrol middle-dose and high-dose groups at 5 d after administration（P＜0.05）；the expression of IL- 6 in serum was significantly decreased in resveratrol low-dose group （P＜0.05）； the protein expressions of RANK-L and RANK in tibia were significantly decreased ，while the protein expression of OPG was increased significantly in resveratrol middle-dose group （P＜0.05）. CONCLUSIONS Resveratrol by intrathecal injection can relieve the inflammation caused by bone cancer pain of rats ， the mechanism of which may be associated with inhibiting the activity of OPG/RANK/RANK-L signal pathway.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To investigate the mechanism of Mayuan tongbian zhitong decoction on improving slow-transmission constipation（STC）in rats by regulating AMP activated protein kinase （AMPK）/endothelial nitric oxide synthase （eNOS）signaling pathway. METHODS The rats were randomly divided into blank group ，model group ，Mayuan tongbian zhitong decoction low-dose，medium-dose and high-dose groups （6，12，18 mg/kg），with 10 rats in each group. Except for blank group ，other groups were given Compound diphenoxylate suspension to induce STC model. After modeling ，blank group and model group were given normal saline intragastrically ，and Mayuan tongbian zhitong decoction groups were given relevant medicine intragastrically ， once a day ，for consecutive 2 weeks. The number of feces and water content of feces in each group were observed before and after treatment；the carbon powder propulsion rate of rats in each group was calculated ；the pathological structure of colon in each group was observed ；the levels of nitric oxide （NO）and nitric oxide synthase （NOS）in colon tissues of rats in each group were detected；the expressions of AMPK ，eNOS，mammalian target of rapamycin （mTOR），tuberous sclerosis complex 1（Tsc-1）， Tsc-2 and eukaryotic promoter 4E binding protein （4ebp）were also detected. The active ingredients of Cannabis sativa ，Citrus aurantium and Rehmannia glutinosa were screened from Mayuan tongbian zhitong decoction. The active ingredients with high Degree value were docked with AMPK and eNOS ，to verify the interaction. RESULTS Compared with before treatment ，the number and water content of feces were increased significantly in Mayuan tongbian zhitong decoction groups （P＜0.05）. Compared with blank group ，carbon powder propulsion rate of model group was decreased significantly （P＜0.05）； colonic structure was disordered ，and a large number of inflammatory cells were seen in submucosa ；the levels of NO and NOS in colon tissue as well as the protein expressions of AMPK ，eNOS，mTOR，Tsc-1，Tsc-2 and 4ebp were increased significantly （P＜0.05）. Compared with model group ，above indexes of Mayuan tongbian zhitong decoction groups （except for NOS in low-dose group ）were reserved significantly （P＜0.05）. In the molecular docking experiment ，the active components with the highest Degree values in C. sativa ，C. aurantium and R. glutinosa were（Z）-3-（4-hydroxy-3-methoxy-phenyl）-N-[2-（4-hydroxyphenyl）ethyl] acrylamide，nobiletin and stigmasterol. The binding energies of AMPK with these three components were －5.15，－4.61 and －4.83 kJ/mol，the binding energies of eNOS with these three components were －6.11，－5.40 and －5.91 kJ/mol. The conformations of these three compounds with AMPK and eNOS were stable and their binding activities were high. CONCLUSIONS Mayuan tongbian zhitong decoction can improve the constipation symptoms and intestinal function in STC model rats ，and its specific mechanism may be related to the inhibition of AMPK/eNOS signaling pathway.关键词：Mayuan tongbian zhitong decoction;slow-transmission constipation;AMPK/eNOS signaling pathway;Mechanism
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发布时间：2022-11-09 - 摘要：OBJECTIVE To evaluate the cost-effectiveness of pyrotinib combined with capecitabine in the second-line treatment of human epidermal growth factor receptor- 2（HER-2）positive advanced breast cancer from the point of view of medical and health system ，and to provide reference for the selection of clinical therapy plan and national health decision. METHODS The dynamic Markov model was constructed on the basis of a multicenter ，open，randomized controlled phase Ⅲ clinical trial in 29 centers in China. The simulation time limit was 8 years，and the cycle was 21 days. The cost-effectiveness of pyrotinib combined with capecitabine （observation group ）were compared with that of lapatinib combined with capecitabine （control group ）in the second-line treatment of HER- 2 positive advanced breast cancer. The incremental cost-utility ratio （ICER）was calculated by using quality-adjusted life year （QALY）as output indicators ，and the sensitivity analysis was carried out to validate the robustness of the results of basic analysis. RESULTS The results of basic analysis showed that compared with control group ，the incremental cost per capita and incremental utility per capita of observation group were 67 953.82 yuan and 0.40 QALYs；ICER was 168 861.89 yuan/QALY，which was lower than the willing to pay （WTP）threshold（217 500 yuan/QALY）represented by 3 times of China ’s per capita GDP in 2020，indicating the treatment plan of the observation group is more cost-effective. The results of single factor sensitivity analysis showed that the proportion of patients treated with trastuzumab or pyrotinib after entering disease progression （PD）status in the control group ，the proportion of patients treated with lapatinib or trastuzumab after entering PD status in the observation group ，the cost of capecitabine and other parameters showed great impact on ICER ，but those parameters didn ’t cause the reverse of basis analysis results. The results of probabilistic sensitivity analysis showed that when the WTP threshold was 217 500 yuan/QALY，the probability that the treatment plan in the observation group was cost-effective was 94.10％. The results of partition survival model analysis were consistent with those of dynamic Markov model. CONCLUSIONS On the premise of taking 3 times of China ’s per capita GDP in 2020 as the WTP lin- threshold， the second-line treatment of HER- 2 positive wang9805@163.com advanced breast cancer with pyrotinib combined with capecitabine is more cost-effective than that with lapatinib combined with capecitabine.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To observe the ther apeutic efficacy and safety of albumin-bound paclitaxel combined with oxaliplatin in the first-line treatment of advanced gastric cancer （GC）. METHODS A total of 90 advanced unresectable GC patients were randomized into observation group and control group ，with 45 patients in each group. Control group was given oxaliplatin combined with tegafur ，and observation group was given albumin-bound paclitaxel combined with oxaliplatin. A chemotherapy cycle last for 21 days，and both groups received 6 cycles of chemotherapy ，and then the follow-up observation was conducted every 2 weeks. Short-term efficacy （after 2 chemotherapy cycles ），mid-term efficacy （after 6 chemotherapy cycles ），tumor marker，long-term efficacy （after follow-up ），quality of life ，the occurrence of ADRs were compared between 2 groups. RESULTS After 2 cycles of treatment ，objective remission rate （ORR）of observation group was significantly higher than that of control group （60.00％ vs. 37.78％，P＜0.05）；there was no statistical significance in disease control rate between the two groups （P＞0.05）. After 6 chemotherapy cycles ，ORR of observation group was significantly higher than that of control group （55.56％ vs. 31.11％，P＜0.05）；there was no statistical significance in disease control rate between the two groups （P＞0.05）；the levels of tumor markers [carcinoembryonic antigen ， carbohydrate antigen （CA）724， CA199， CA242] in observation group were significantly lower than those of control group （P＜0.05）. After the follow-up period ，the median progression-free survival [ 8.78 （95％CI：6.94-11.01）months] and the median overall survival [ 13.02（95％CI：12.78-15.62）months] of observation group were significantly longer than those [ 6.99（95％CI：3.67-10.88）months and 10.42（95％CI：8.72-13.22）months] of control group （P＜ 0.05）. The score of body dimension in the observation group was significantly higher than that in the control group （P＜0.05）. Except for peripheral neurotoxicity ，there was no significant difference in the incidence of ADR between 2 groups（P＞0.05）. CONCLUSIONS Albumin-bound paclitaxel combined with oxaliplatin has a good effect and safety in the first-line treatment of advanced unresectable GC.
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发布时间：2022-11-09 - 摘要：OBJECTIVE To introduce the construction of undergraduate specialty of clinical pharmacy based on the concept of outcome-based education （OBE），and to provide new idea and enlightenment for the construction of undergraduate specialty of clinical pharmacy in Chinese universities. METHODS Through the establishment and construction of training objectives and graduation requirements ，teaching reform was designed and implemented ，and the construction of teaching support system and teaching quality assurance system were completed. RESULTS The clinical pharmacy department of our university established the training direction of clinical pharmacy talents under the guidance of post competence ，including clarifying the training needs of undergraduate talents based on the overall requirements of national undergraduate education ；defining the social and industrial needs of clinical pharmacy talents based on the normative documents or concepts of clinical pharmacy ；clarifying the post and ability needs of clinical pharmacy talents based on the investigation of graduates and clinical pharmacists ；clarifying the development needs of clinical pharmacy based on the current situation and trends at home and abroad ；forming characteristic training objectives combined with the regional characteristics and school positioning ， so as to construct training objectives and graduation requirements. The OBE concept was introduced into the undergraduate teaching reform of clinical pharmacy ；the pharmacy talent training direction were established under the guidance of post competence ；the training system was designed by reverse design method；a training mode of both innovation and practical ability was built so as to promote teaching reform ，strengthen the construction of grass-roots teaching organizations and teaching staff ， and improve the construction of teaching quality assurance system. CONCLUSIONS The undergraduate training mode of clinical pharmacy specialty based on the concept of OBE is helpful to improve students ’personal comprehensive quality and professional knowledge and skills. The established undergraduate training model of clinical pharmacy specialty is in line with the modern educational concept and social needs ，and provides theoretical basis and practical experience for the training mode of clinical pharmacy professionals.关键词：Clinical pharmacy;training system;outcome-based education;social demands;undergraduate education
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发布时间：2022-11-09 - 摘要：OBJECTIVE To analyze th e evaluation methods of the skill ，adherence and effectiveness of medication in bronchial asthma （hereinafter referred to as “asthma”）patients from a pharmacist perspective ，and to provide reference for pharmacists to carry out clinical intervention researches and management of asthma patients. METHODS Referring to diagnosis and treatment guidelines ，evidence-based medicine literature and clinical practice experience ，the evaluation methods of asthma patients ’ medication with clinical value were expounded from three aspects including medication skill （inhalation technology ），adherence and effectiveness. RESULTS Inhalation technique rating form was an important evaluation method of medication skills in asthma patients. Medication adherence could be evaluated by Morisky Medication Adherence Scale or the Medication Adherence Report Scale for Asthma. Effectiveness evaluation methods contained direct evaluation indexes （such as clinical manifestations ，situation of acute exacerbation and relieving medication ，examination indexes such as pulmonary function indexes and fractional concentration of exhaled nitric oxide ）and indirect evaluation tools （i.e. various scales ，including Asthma Control Test ，Children-Asthma Control Test，the Test for Respiratory and Asthma Control in Kids ，asthma related quality of life scales ，etc.）CONCLUSIONS The combination of the evaluation methods of medication skill ， adherence and effectiveness contributes to assessing the pharmacotherapy effect of asthma patients. Pharmacists should apply and perfect these evaluation methods in practice ，so as to conduct better pharmaceutical intervention on asthma patients.关键词：asthma;medication skill;adherence;Effectiveness;evaluation methods
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发布时间：2022-11-09 - 摘要：OBJECTIVE To evaluate the effects of pharmaceutical interventio n led by clinical pharmacists on medication appropriateness of elderly inpatients. METHODS A non-randomized concurrent controlled trial was carried out. Elderly patients admitted to two treatment groups in the geriatric department of Yancheng First People ’s Hospital since June 2021 were selected as the research objects. According to the inclusion and exclusion criteria ，the first 40 patients were selected from each of the two treatment groups （according to the order of admission time ）and set as the control group or the intervention group. The control group received routine treatment and nursing services ，and the intervention group additionally received pharmaceutical intervention led by clinical pharmacists on the basis control group. Clinical pharmacists found potential inappropriate medication （PIM）and put forward suggestions on optimization of medication regimen. American Geriatrics Society 2019 Updated AGS Beers Criteria ® for PIM Use in Older Adults （hereinafter referred to as “Beers criteria ”）and the Criteria of PIMs for Older Adults in China 2017 Edition （hereinafter referred to as “Chinese criteria ”）were used as reference tools for drug use review. The medication appropriateness index （MAI）total scores （main evaluation indicator ），the number of PIMs ，the number of drugs used ，the length of hospital stay ，the number of drug-related adverse events during hospital stay ，the number of drug regimen optimization suggestions by pharmacists ， and implementation rate of E-mail：zhihuadou@163.com optimization suggestions adopted by clinicians were compared between 2 groups at admission and at discharge. RESULTS At admission ，there were no statistically differences in MAI total scores，the number of PIMs based on Beers criteria ，the number of PIMs based on Chinese criteria or the number of drugs used between 2 groups（P＞0.05）. At discharge ，there were no statistically differences in the number of PIMs based on Chinese criteria and the length of hospital stay between 2 groups（P＞0.05），but the MAI total scores ，the number of PIMs based on Beers criteria and the number of drugs used in the intervention group were lower than those in the control group （P＜0.05）. In the intervention group，the proportion of drugs recorded as “inappropriate medication ”at admission （34.5％）was significantly higher than that at discharge（19.5％）（P＜0.05）. The difference between the number of drugs discharged from hospital and the number of drugs admitted to hospital in the control group [ 3（1-4.8)] was significantly higher than that in the intervention group [ 1（0-2.8)]（P＝ 0.012）. Compared with admission ，the proportion of drugs recorded as “inappropriate medication ”in the intervention group at discharge was significantly decreased on the basis of “effectiveness”dimension and “course”dimension （P＜0.05）. During hospitalization，clinical pharmacists put forward 70 optimization suggestions of drug regimen for the intervention group ，among which 39 suggestions were adopted and implemented by clinicians ，with an implementation rate of 55.7％. CONCLUSIONS The pharmaceutical intervention led by clinical pharmacists can improve overall appropriateness of drug use in the elderly inpatients using MAI as main evaluation indicator.关键词：pharmaceutical intervention;elderly inpatients;medication appropriateness;potential inappropriate medication
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发布时间：2022-11-09 - 摘要：Piperine is a kind of amide alkaloids presenting in Piper nigrum L.，which has the pharmacological action such as protecting cardiovascular system ，regulating glucose and lipid metabolism ，anti-tumor，improving nervous system diseases ， anti-inflammation and so on. This paper summarized the pharmacological action and mechanisms of piperine in recent years and found that piperine ，as the main active ingredient of P. nigrum ，could protect the cardiovascular system by reducing inflammation and oxidative stress ；improve mitochondrial function through anti-inflammatory and antioxidant effects ，thereby regulate glucose and lipid metabolism ；play an anti-tumor role by mediating the signaling pathways of Wnt/β-catenin，NF-κB/Nrf-2/KeAP-1/HO-1， PI3K/Akt，TGF-β1/Smad2/ERK1/2；improve neurological diseases by inhibiting autophagy ，relieving inflammation ，improving antioxidant，inhibiting neuronal apoptosis and regulating the expression of related proteins in neurons ；play an anti-inflammatory effect by inhibiting the activity of NF-κB and other signaling pathways and reducing the expression of inflammation-related proteins. However，the mechanism of action of piperine is not perfect ，and most of the studies have been confined to the pharmacological level or a certain signaling pathway and a certain target ，without being able to elucidate the interconnection between the relevant signaling pathway and the specific target from a holistic perspective. In the follow-up ，the specific targets of piperine can be identified and clinical trials can be carried out to provide support for the clinical application of piperine.关键词：piperine;amide alkaloids;pharmacological action;Cardiovascular;Anti-tumor
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发布时间：2022-11-09 - 摘要：Gambogic acid is the main active component of Garcinia hanburyi Hook. f. ，which can inhibit the growth of a variety of tumor cells. However ，its low solubility ，short half-life and poor stability limit its clinical application to a certain extent. In order to improve the above shortcomings and improve the bioavailability of gambogic acid ，many studies have used covalent binding and physical encapsulation methods to obtain a new gambogic acid delivery system with targeting ，high permeability ，stability， biocompatibility，in vivo long circulation and other properties ，such as polymer prodrug delivery system ，anoxic prodrug delivery system，magnetic field responsive prodrug delivery system ，multi environment sensitive prodrug delivery system ，bionic nano drug delivery system. This paper reviews the new drug delivery system and its characteristics of gambogic acid. The results show that the design of drug carrier has greatly improved the defects of gambogic acid ，and the introduction of more responsive groups into gambogic acid drug carrier may make it achieve better antitumor effect.关键词：gambogic acid;drug delivery system;bioavailability;Clinical application
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发布时间：2022-11-09
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