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Mechanisms of celastrol for ovarian cancer: based on quantitative proteomics MA Qihong, SHI Yuanyuan, CHEN Fangfang, WU Kang, BU Zixuan, LU Tiangong 2023, 20(7): 721-727.  DOI: 10.19803/j.1672-8629.20230197 Abstract ( 87 )   PDF (3154KB) ( 62 )   Objective To explore the inhibitory effect of celastrol on proliferation and migration of ovarian cancer cells and the molecular mechanism. Methods The ability of celastrol to inhibit the proliferation and migration of ovarian cancer cells was confirmed by MTT and wound healing assays. Proteomics was performed to discriminate the differentially expressed proteins (DEPs) associated with the inhibitory effects of celastrol on ovarian cells. EMT markers (cadherin switch) and key proteins that regulated cell migration (CD44 and HMGB) in ovarian cancer cells were detected using Western blot. The effect of celastrol on reactive oxygen species (ROS) production in ovarian cancer cells was determined via immunofluorescence measurement. Results Celastrol significantly inhibited the proliferation and migration of SKOV3 and OVCAR3 cells. 396 DEPs were identified in ovarian cells treated with celastrol (126 up-regulated and 270 down-regulated) based on proteomics. The analysis of both GO and KEGG pathways showed that the multi-target anti-tumor activity of celastrol was related to cell migration, inflammation and hypoxia. Celastrol inhibited EMT by down-regulating N-cadherin and up-regulating E-cadherin. Celastrol also retarded the healing of ovarian cancer cells by inhibiting the expressions CD44, HMGB1 and HMGB2. Conclusion Proteomics studies have found that celastrol has multi-targeted anti-ovarian cancer activities. Celastrol can inhibit the migration and proliferation of ovarian cancer cells by inhibiting the process of EMT and inducing the production of ROS. References | Related Articles | Metrics

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Emodin -8-O-β-D-glucoside combined with paclitaxel inhibits the viability and metastasis of human breast cancer cells YAN Yishu, ZHAO Yan, LU Tiangong, SUN Zhenxiao 2023, 20(7): 728-734.  DOI: 10.19803/j.1672-8629.20230243 Abstract ( 55 )   PDF (1974KB) ( 59 )   Objective To investigate the effects of emodin-8-O-β-D-glucoside (EG) combined with paclitaxel (PTX) on the viability and metastasis of human breast cancer cells. Methods MTT assay was used to detect the cell viability of EG, PTX alone and concomitant administration on MCF 7 and MDA-MB-231 cells, and the combination index (CI) value was calculated to evaluate the effects of the two drugs; Transwell assay was used to detect the metastasis ability of the two drugs combinations on two kinds of breast cancer cells; The mRNA expression level of metastasis-associated genes (MMP2、MMP9, CDH1, CDH2, Vimentin and Snail) detected by Quantitative Real-time PCR. Results EG and PTX significantly inhibit the survival of human breast cancer MCF 7 and MDA-MB-231 cells (P<0.01), and the two drugs exhibited a synergistic effect at experimental concentrations; The combination of EG (240 mmol·L-1) and PTX (5 nmol·L-1) can substantially suppress the metastasis of human breast cancer cells (P< 0.01); the expressions of matrix metalloproteinase genes MMP-2 and MMP-9 (P<0.01), EMT-related genes Vimentin (P<0.01) and Snail (P<0.01, P<0.05) in breast cancer cells was significantly down-regulated through the combination of two drugs; the combination can up-regulated the expression level of CDH1 in MCF 7 cells and down-regulated the expression level of CDH2 in MDA-MB-231 cells (P<0.01). Conclusion EG combined with PTX can synergistically inhibit the viability and metastasis of human breast cancer cells. References | Related Articles | Metrics

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Screening and in vitro study of traditional Chinese medicines against lung adenocarcinoma based on EGFR YU Yuehua, ZHAO Yan, LU Tiangong, SUN Zhenxiao 2023, 20(7): 735-741.  DOI: 10.19803/j.1672-8629.20230273 Abstract ( 56 )   PDF (2480KB) ( 68 )   Objective Using molecular docking virtual screening and TCMSP to screen out traditional Chinese medicines and sections that may have anti-lung adenocarcinoma effects, and studying it’s effects against lung adenocarcinoma in vitro. Methods Small molecule compounds of TCSMP database were screened based on Lipinski’s rule of five and ADME were docked with EGFRL858R/T790M/C797S to obtain candidate traditional Chinese medicines or sections against lung adenocarcinoma through the frequency of docking molecules; preliminary validation of anti-lung adenocarcinoma activity and in vitro screening of extract of candidate traditional Chinese medicines or sections against lung adenocarcinoma using MTT method. Further optimization of candidate traditional Chinese medicines or sections against lung adenocarcinoma through differential killing effects of drugs on human lung adenocarcinoma cells NCI-H1975 and human lung fibroblast cells HPF; flow cytometry was used to detect the effects of drugs on apoptosis and mitochondrial membrane potential of NCI-H1975; Western blot was used to detect the effects of drugs on protein expression and phosphorylation of EGFR and its downstream target AKT. Results Through molecular docking results and literature research to screen 8 candidate traditional Chinese medicines (Myristicae Semen, Forsythiae Fructus, Stemonae Radix, Lobeliae Chinensis herba, Curcumae Radix, Piperis Longi Fructus, Polygonati Odorati Rhizoma and Anemarrhenae Rhizoma) and 3 parts of traditional Chinese medicine (total alkaloids of Radix Stemonae, total saponins of Anemarrhenae Rhizoma and total saponins of Gynostemma Pentaphyllum); in vitro experiment studies found that extract of Anemarrhenae Rhizoma and Forsythiae Fructus, total alkaloids of Radix Stemonae and total saponins of Anemarrhenae Rhizoma had strong killing effects on NCI-H1975, with a certain time and dose dependent effect. At the same dose, extract of Forsythiae Fructus and total saponins of Anemarrhenae Rhizoma had weak killing effects on HPF. Further research found that they can decrease mitochondrial membrane potential, induce apoptosis and inhibit the activation of the EGFR-PI3K/AKT signaling pathway of NCI-H1975. Conclusion Based on the specific target of lung adenocarcinoma, the database of traditional Chinese medicines and components can be used to virtually screen anti-lung adenocarcinoma traditional Chinese medicines or sections through molecular docking and other ways, and in vitro experiments were used to detect differential effects of traditional Chinese medicines or sections against lung adenocarcinoma on lung adenocarcinoma cells and normal lung cells, further optimize the screening results, and reveal it’s anti-lung adenocarcinoma mechanism. References | Related Articles | Metrics

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Evaluation of hepatotoxicity of periplocin based on zebrafish model CHEN Linzhen, WANG Xuan, ZHANG Xiaomeng, MA Zhiqiang, LU Shan, WU Jiarui, ZHAO Chongjun, ZHANG Bing 2023, 20(7): 742-748.  DOI: 10.19803/j.1672-8629.20230022 Abstract ( 51 )   PDF (2887KB) ( 46 )   Objective To explore the toxic target organs and potential mechanism of periplocin based on a zebrafish model. Methods Zebrafish(4 days post fertilization,4 dpf) were exposed to different concentrations of periplocin solution for 24 h (the low concentration was 1 μg·mL-1and the high concentration was 1.5 μg·mL-1), and the fatality rate of periplocin for zebrafish was calculated. After twenty-four hours of exposure to a sub-lethal dose, the hepatotoxicity of periplocin was evaluated based on changes of areas of the liver, aeridine orange staining, liver histopathologic sections, and changes in alanine aminotransferase (ALT) and aspartic aminotransferase (AST) activities. Furthermore, the potential mechanism of periplocin hepatotoxicity was predicted via network pharmacology and molecular docking techniques before being verified by real-time PCR. Results The sublethal dose of periplocin for zebrafish was 1.612 6 μg·mL-1. Under sub-lethal dose exposure, periplocin treatment could result in reduced liver areas of zebrafish and obvious apoptosis in the liver compared with the control group. Histopathological section results showed that periplocin exposure induced loose and disordered arrangement of liver cells as well as obvious vacuoles. In addition, periplocin could significantly increase the activities of ALT and AST in zebrafish, which proved the significant hepatotoxicity of periplocin in zebrafish. Network pharmacology indicated that periplocin-induced hepatictoxicity was related to the 21 potential targets and the top five targets of PPI protein interaction network were STAT3, HSP90AA1, HIF1A, NOS3 and MTOR. KEGG results showed that periplocin hepatotoxicity might be related to HIF-1 signaling pathway, PI3K/Akt signaling pathway, and calcium signaling pathway, as was confirmed by RT-PCR. Conclusion Periplocin-induced hepatotoxicity is associated with the disturbance of HIF-1 and PI3K/Akt signaling pathways. References | Related Articles | Metrics

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Antifatigue effect of ophiopogonin D on exhaustive swimming in mice SHEN Ningning, LIU Yufu, RU Yi, SHI Zhuo, YANG Chunqi, NI Zhexin, XIAO Chengrong, MA Zengchun, WANG Yuguang, GAO Yue 2023, 20(7): 749-753.  DOI: 10.19803/j.1672-8629.20230053 Abstract ( 37 )   PDF (1543KB) ( 58 )   Objective To observe the anti-fatigue effect of Ophiopogonin D by constructing a mouse model of exhaustive swimming exercise. Methods The mice were divided into three batches. The control group, swimming model group, low-dose (Ophiopogonin D 20 mg·kg-1), medium-dose (Ophiopogonin D 40 mg·kg-1) and high-dose administration groups (Ophiopogonin D 60 mg·kg-1) were established. The weight-bearing swimming experiment was performed after a week of continuous intragastric administration. Serum creatine kinase, urea and triglyceride were measured via swimming test on the second day. One week after the second and third batches of mice were administered with the above dosages, the non-weight-bearing swimming experiment was conducted. The effects of high, medium and low doses of Ophiopogonin D on body weight, blood lactic acid and liver glycogen of mice were analyzed using the blood lactic acid detection kit, liver glycogen assay kit and otherwise. Results Compared with the swimming model group, the duration of weight-bearing swimming Ophiopogonin D mice was prolonged, the liver glycogen content was increased, the serum creatine kinase level was decreased, the serum triglyceride content was increased, and the area under the blood lactic acid curve was decreased after swimming. All the above indexes were of statistical significance (all P<0.05). Serum urea nitrogen decreased, but the change was not statistically significant (P>0.05). Conclusion Ophiopogonin D can significantly enhance exercise endurance, reduce lactic acid accumulation and increase glycogen reserve in mice. References | Related Articles | Metrics

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Acute toxicity of proline Danshensu borneol ester in mice WANG Rong, LIU Ziqun, WANG Nana, TAN Xiong, ZHANG Yixin, YANG Kuan, QIN Bei 2023, 20(7): 754-757.  DOI: 10.19803/j.1672-8629.20220529 Abstract ( 40 )   PDF (2007KB) ( 56 )   Objective To explore the acute toxicity of anti-hypertensive drug proline-Danshensu borneol ester-in mice, and to evaluate its safety. Methods Twenty-four mice were randomly divided into the test group and control group. The maximum tolerated dose (MTD) was determined via single intragastrical administration of the maximal concentration of proline Danshensu borneol ester (150 mg·mL-1). Toxic reactions, body weight and intakes of foods and water were observed for seven consecutive days until the mice were sacrificed. Visceral changes were observed and index of the heart, liver, kidney and lung were recorded. Pathological histology was observed via HE staining. Results There was no death of mice after intragastrical administration of different concentrations of proline Danshensu borneol ester. Compared with the control group, the daily activities, body weight and intakes of foods and water in the test group of mice were not significantly different (P>0.05), so were the indexes of the liver, kidney or lung (P>0.05). The heart indexes of male mice in the test group were not significantly different from those of the control group (P>0.05), but the heart indexes of female mice were significantly decreased (P<0.05) and myocardial cells were disorderly. Conclusion The MTD of proline Danshensu borneol ester in mice is orally 3 000 mg·kg-1, which leads to low toxicity in mice. References | Related Articles | Metrics

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Rats safety evaluation of acteoside NIE Yunan, ZHANG Li, SHAO Mingxiang, GAO Li, YAN Ming 2023, 20(7): 758-762.  DOI: 10.19803/j.1672-8629.20220344 Abstract ( 34 )   PDF (1455KB) ( 42 )   Objective To preliminarily evaluate the safety of acteoside through toxicity tests of single and repeated dose, thus laying the foundation for in-depth and comprehensive safety evaluation. Methods Single dose toxicity test: SD rats were randomly divided into a solvent control group and a medication group(5 000 mg·kg-1), and were administered orally in single dose. The general clinical symptoms,mortality,and weight of rats within 14 days were observed and recorded,and the main organs were visually observed.Repeated dose toxicity test: SD rats were randomly divided into a solvent control group, and acteoside low (100 mg·kg-1), medium (500 mg·kg-1), and high dose group(2 000 mg·kg-1), 30 in each group, and were continuously administered for 28 days and recoverded for 28 days. Their general clinical symptoms, body weight, food intake, urine routine, and other related indicators were observed and tested. Results The single dose toxicity test results showed that compared with the solvent control group, there were no deaths or abnormalities in rats; there was no statistically significant difference in body weight (P>0.05), and there were no visible lesions in organ tissues. The repeated toxicity test results showed that compared with the solvent control group, there was no statistically significant difference in body weight, food intake, coagulation indicators, organ wet weight and organ coefficient of rats(P>0.05). There was no toxicological effect on hematology, liver function and kidney function, and there was no obvious histopathology change related to drug administration in the high dose group; the positive detection rate of white blood cells and ketone bodies in the urine routine of female animals in the high-dose group was relatively high (P<0.05 or P<0.01), indicating reversibility. Conclusion In the single dose toxicity test, the maximum tolerated dose (MTD) of single dose for acteoside was greater than 5000 mg·kg-1, and in the repeated dose toxicity test, the no observed adverse effect level (NOAEL) of acteoside was 500 mg·kg-1. References | Related Articles | Metrics

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Evaluation of dissolution curves of indapamide tablets between generics and reference formulation FU Mengjun, YAO Huihui, ZHU Kexu, WANG Xinyuan, YAO Shangchen 2023, 20(7): 763-768.  DOI: 10.19803/j.1672-8629.20230058 Abstract ( 53 )   PDF (1698KB) ( 68 )   Objective To compare the dissolution curves of indapamide tablets from different manufacturers and its reference formulation. Methods The dissolution of 13 types of generics of indapamide tablets and its reference formulation in different pH media was determined via a dissolution tester and HPLC before the dissolution curve was drawn. The column was Agilent Poroshell 120 SB-C18, the mobile phase was methanol-water-glacial acetic acid (45：55：0.1) at a flow rate of 1 mL·min-1, the detection wavelength was 240 nm, the column temperature was 40℃, and the injection volume was 5 μL. The stirring paddle method was adopted, with the volume of the dissolution medium at 900 mL at the rotating rate of 50 r·min-1. The dissolution media were water, hydrochloric acid solution (pH 1.2), acetic acid-sodium acetate buffer solution (pH 4.0) and phosphate buffer solution (pH 6.8). The similarity of dissolution profiles was evaluated by calculating the similar factor (f2). Results In different dissolution media, the dissolution curves of generic drugs from only a few manufacturers were similar to those of the reference formulation, but most of the dissolution curves of generic drugs from different manufacturers were not similar to those of the reference formulation. Conclusion There are differences in the dissolution of indapamide tablets produced by different manufacturers. It is recommended that relevant manufacturers improve the excipients and production processes that affect the dissolution of the preparation to improve the quality of generic drugs. References | Related Articles | Metrics

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Determination of seven main components in aqueous extract of Bupleuri Radix-Paeoniae Alba Radix by UPLC-PDA WU Lingfang, TIAN Wei, MA Yongben, GAO Le, SUN Zheng, WANG Xinguo, NIU Liying 2023, 20(7): 769-774.  DOI: 10.19803/j.1672-8629.20220715 Abstract ( 28 )   PDF (1448KB) ( 44 )   Objective To establish a method for simultaneous determination of gallic acid, paeoniflorin, albiflorin, benzoyl paeoniflorin, saikosaponin A, saikosaponin C and saikosaponin D in the aqueous extract of Bupleurum and Paeoniae Alba by UPLC-PDA. Methods The Waters ACQUITY UPLC BEH C18 (2.1 mm×100 mm, 1.7 μm) column was used with the mobile phase composed of acetonitrile - 0.1% acetic acid aqueous solution under gradient elution. The flow rate was 0.2 mL·min-1 at detection wavelengths of 210 nm for saikosaponin A, saikosaponin C and saikosaponin D, 237 nm for paeoniflorin, albiflorin and benzoyl paeoniflorin, and 278 nm for gallic acid. The column temperature was 30℃ while the injection volume was 8 μL. Results The linear ranges of gallic acid, paeoniflorin, albiflorin, benzoyl paeoniflorin, saikosaponin A, saikosaponin C and saikosaponin D were 0.018~0.18 μg (r=0.999 9), 0.047~0.47 μg (r=1), 0.52~5.18 μg (r=0.999 9), 0.021~0.21 μg (r=0.999 9), 0.043~0.43 μg (r=0.999 9), 0.073~0.73 μg (r=0.999 9), and 0.042~0.42 μg (r=0.999 6) respectively. The average recovery (n=9) ranged from 99.94 to 101.47%, and the RSD was less than 2%. Conclusion This method is rapid, accurate and reproducible. It can be used for quality control of decoction of Radix Bupleuri-Paeoniae Alba. References | Related Articles | Metrics

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Preclinical safety evaluation of Jinkui Shenqi pills ZUO Zeping, TIAN Yingying, XU Yi, JIANG Kewu, YANG Shuo, YANG Hairun, ZHANG Zhicong, CAO Xinyao, WU Xiaoru, WANG Zhibin 2023, 20(7): 775-782.  DOI: 10.19803/j.1672-8629.20220512 Abstract ( 93 )   PDF (2219KB) ( 85 )   Objective To investigate the toxicity of Jinkui Shenqi pills after single administration and after 26 weeks of repeated administration so as to provide reference for safe clinical use. Methods ICR mice were given intragastrically the highest concentration and maximum dose of Jinkui Shenqi pills before the animal toxicity was observed 14 days after administration (11.2 g·kg-1 BW, which was 102 times the clinical human dose). SD rats were randomly divided into the control group and Jinkui Shenqi pill high-dose, medium-dose and low-dose groups (5.6 g·kg-1 BW, 2.8 g·kg-1 BW, 1.4 g·kg-1 BW, which were 51 times, 25.5 times, 12.75 times the clinical human dose, respectively), gavaged twice a day for 26 weeks. Thirteen weeks and 26 weeks into administration and during the four weeks of recovery, the body weight, food intake, hematology and coagulation indexes of the rats were detected by a blood analyzer, and the related biochemical indexes by an automatic biochemical analyzer. Histopathological examination was conducted to evaluate the potential toxicity, reversibility of toxicity, and possible secondary and/or delayed effects of the drug. Results After single-dose toxicity test and during the 14 days of observation, there was no abnormality or death among the rats. The maximum dose of administration (MFD) was 11.2 g·kg-1 BW, which was equivalent to 102 times the clinical human dose. Twenty-six weeks of continuous intragastric administration of Jinkui Shenqi pills did not cause any serious adverse reactions among the SD rats. No histopathological changes related to drug toxicity were observed in major organs of the rats. There was no delayed drug toxicity after drug withdrawal. The NOAEL was 5.6 g·kg-1 BW·d-1, which was 51 times the clinical human dose. Conclusion Jinkui Shenqi pills cause neither acute toxic reactions nor potential/secondary/delayed toxic reaction after long-term administration. It is safe at the therapeutic doses. References | Related Articles | Metrics

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Formability and mechanism of breast nodule pain-alleviating gel plaster for the treatment of breast hyperplasia SU Yuefen, ZHENG Jingrou, GONG He, XIE Guangtong, ZHANG Jie, SAI Chunmei 2023, 20(7): 783-790.  DOI: 10.19803/j.1672-8629.20220569 Abstract ( 41 )   PDF (2401KB) ( 45 )   Objective To optimize the matrix formulation, prepare a breast nodule pain-alleviating gel plaster (BNPGP), and explore its potential mechanism for the treatment of breast hyperplasia via network pharmacology and molecular docking technology. Methods With the “initial adhesion, cohesive strength and comprehensive sensory organs” as evaluation indexes, the matrix prescription of BNPGP was optimized by orthogonal design, and its formability was investigated. All the targets of the active components and breast hyperplasia were retrieved from such databases as TCMSP, Targetnet, Genecards, OMIM with network pharmacology. The Venny tool was used to screen the intersection targets. The drug-active component-target network was established with Cytoscape software, and protein-protein interaction (PPI) analysis was performed on the intersection targets using String database. KEGG and GO pathway enrichment analysis was performed on the intersection targets using Metascape database. Finally, molecular docking verification was carried out with AutoDockTool and PyMoL software. Results Orthogonal test optimized the matrix prescription of BNPGP as follows: carbomer 20 mL at a swelling ratio of 1 : 40, 20 mL drug solution of 3 g·mL-1, 7 mL glycerol, and 1.5 mL methyl p-hydroxybenzoate of 0.1 g·mL-1. Based on network pharmacology, 45 effective components of BNPGP and 49 intersection targets between active components and breast hyperplasia were screened, including ESR1 and EGFR, which were involved in regulating Pathways in cancer, Proteoglycans in cancer, and Chemical carcinogenesis-receptor activation in the treatment of breast hyperplasia. Molecular docking showed that the main active components-luteolin and kaempferol-had strong binding ability to core targets EGFR and AR. Conclusion BNPGP prepared according to this optimal process has uniform appearance, good adhesion and formability, which can provide reference for the development of processes. BNPGP may play a role in the treatment of breast hyperplasia by regulating hormone levels and cell cycle, inhibiting angiogenesis by regulating key targets such as EGFR, AR, STAT3, and intervening in EGFR/PI3K/Akt, JAK/STAT signaling pathways. References | Related Articles | Metrics

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Risks to safety of vitamin B6 injection YANG Le, XIA Dongsheng, WANG Tao 2023, 20(7): 791-794.  DOI: 10.19803/j.1672-8629.20230067 Abstract ( 190 )   PDF (1285KB) ( 215 )   Objective To analyze the risks to safety posed by vitamin B6 injection in China in order to provide reference for clinical rational drug use. Methods The individual cases of adverse drug reactions retrieved from China adverse drug reaction database (from January 1, 2004 to June 30, 2019) and WHO Vigilyze (from inception to January 31, 2023), and other databases (from inception to December 31, 2020) were analyzed. Results The risk posed by vitamin B6 injection, general disorders, and related cutaneous and gastrointestinal system damage deserved more attention. Conclusion Drug marketing authorization holders should reinforce the safety monitoring of vitamin B6 injection, update the drug labeling in a timely manner and promote the rational use of medicines. References | Related Articles | Metrics

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After-marketing safety of coenzyme Q10 for injection MENG Kangkang, LIU Saiyue 2023, 20(7): 795-798.  DOI: 10.19803/j.1672-8629.20230047 Abstract ( 129 )   PDF (1354KB) ( 139 )   Objective To analyze the data on monitoring of safety of coenzyme Q10 injection and provide reference for clinical rational drug use. Methods Reports of adverse drug reactions/events of coenzyme Q10 injection between January 1, 2004 and September 30, 2020 were retrieved from China adverse drug reaction monitoring database and from domestic literature database between inception to June 30, 2021. And the domestic labeling on Q10 injection were analyzed. Results The national adverse drug reaction monitoring database received 3 097 case reports of adverse reactions/events related to coenzyme Q10 injection, including 320 reports of serious cases(10.4%). Systemic injury, injury to the respiratory system, immune disorders and infections among the severe cases were more serious than among the common cases. Severe allergic reactions to coenzyme Q10 injection deserved more attention. Instructions on safety in the labeling were implicit. Conclusion Medical institutions should keep updated on the safety information in revised instructions and comply with the instructions. Drug manufacturers should be committed to pharmacovigilance and take effective measures to reduce drug risks. References | Related Articles | Metrics

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Efficacy and safety of Houpupaiqi Mixture in the treatment of postoperative lieus: a Meta-analysis ZHANG Lei, LYU Jian, XIE Yanming 2023, 20(7): 799-806.  DOI: 10.19803/j.1672-8629.20211066 Abstract ( 59 )   PDF (1498KB) ( 69 )   Objective To systematically review the efficacy and safety of Houpupaiqi Mixture in the treatment of postoperative lieus. Methods Eight databases, including CNKI, Wanfang , VIP , CBM, Cochrane Library, PubMed , Embase and Web of Science, were searched for RCTs that used Houpupaiqi Mixture to treat postoperative lieus and were published from inception to April 30,2021. Meta-analysis was conducted using the Cochrane Handbook for Systematic Reviews of Interventions(Version 5.1) and Revman 5.3. Results Thirteen RCTs were included, involving 1 836 patients (1 199 in the experimental group and 637 in the control group). Meta-analysis showed that Houpupaiqi Mixture combined with conventional treatments was more effective than conventional treatments alone in shortening the first anal exhaust time[MD=-8.41, 95%CI(-10.37, -6.45), P<0.000 01], the first defecation time [MD= -11.79, 95% CI(-15.14, -8.44), P<0.000 01], and hospital stay [MD=-2.35, 95% CI(-3.08, -1.62), P<0.000 01]. And Houpupaiqi Mixture was better than the blank group in shortening the first defecation time [MD=-5.27, 95% CI(-7.10, -3.45), P<0.000 01]. The adverse reactions included nausea, vomiting and diarrhea. Symptoms of nausea and vomiting were mostly mild, and disappeared without treatment. Conclusion Houpupaiqi Mixture used alone or in combination with conventional treatments for postoperative lieus has many advantages. Most of the adverse reactions are mild and can disappear by themselves. However, due to the low quality of the studies included, our conclusions need to be confirmed by RCTs up to the international standards with a large sample size and rigorous design. References | Related Articles | Metrics

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Automatic monitoring and assessment of antibiotics-related thrombocytopenia HUANG Cuili, GAO Ao, WANG Jiaxi, GUO Haili, XU Xiaohan, CHENG Yinchu, GUO Daihong 2023, 20(7): 807-811.  DOI: 10.19803/j.1672-8629.20220348 Abstract ( 115 )   PDF (1401KB) ( 108 )   Objective To find out about the clinical characteristics and risk factors for severity of antibiotics-related thrombocytopenia among inpatients. Methods Using the “ADE active surveillance and assessment system-Ⅱ” ( ADE-ASAS-Ⅱ), the electronic medical data on inpatients treated in our hospital between June 1, 2020 and May 31, 2021 was retrospectively monitored. Patients who met the standards were automatically identified before alarm was given. After the alarm, patients were manually assessed, and the clinical characteristics, drug distribution and risk factors for severity of antibiotics-related thrombocytopenia were analyzed. Results A total of 86 452 inpatients were included in the surveillance, with 1 606 system alerts. After screening, The age of the 204 positive cases averaged (62.8±15.46) years, and thrombocytopenia mostly occurred within 7 days of medication, involving a total of 189 cases (92.65%). The drugs involved were of 11 categories and 22 types. Most of the cases of thrombocytopenia were caused by cephalosporins (135 cases, 66.20%). The top three drugs were cefoperazone sulbactam (39 cases, 19.12%), cefuroxime (32 cases, 15.69%) and flomoxef (21 cases, 10.29%). Meropenem was the most likely drug responsible for severe thrombocytopenia (30 cases, 20%). Complications with abnormal liver function (OR=3.17, 95%CI:1.07~9.38), admissions to ICU (OR=3.17, 95%CI: 1.19~8.46), co-administration with antibiotics (OR=3.28, 95%CI: 1.38~7.79) and combination of antithrombotic agents (OR=2.80, 95%CI: 1.11~7.07) could increase the risk of severe thrombocytopenia. Among these cases, 145 had their drugs withdrawn, while the rest were mostly treated with dexamethasone (28 cases) and recombinant human thrombopoietin (25 cases). Conclusion There are many antibacterial drugs that cause thrombocytopenia. In clinical use of these drugs, the clinical manifestations of patients and the platelet count need to be monitored. Early warning and precautions are critical to high-risk groups and the combination of high-risk drugs. References | Related Articles | Metrics

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Evaluation of individualized parenteral nutrition delivery CHEN Jie, QIN Kan 2023, 20(7): 812-816.  DOI: 10.19803/j.1672-8629.20230036 Abstract ( 62 )   PDF (1378KB) ( 73 )   Objective To evaluate the clinical efficacy of clinical pharmacists’ involvement in the design of a total nutrition admixture (TNA) formulary to provide individualized dosing regimens for patients. Methods The clinical data of patients with digestive disorders treated with parenteral nutrition support between January 1, 2020 and December 15, 2021 was retrospectively studied. There were 49 cases in the individualized total nutrition admixture infusion group (individualized group) in which clinical pharmacists participated and another 56 cases in the single bottle infusion of nutritional drugs group (single bottle group). Such data as the nutritional indexes, liver and kidney function indicators, complications, adverse reactions, and hospital stay were collected. Results The levels of prealbumin, retinol-binding protein. C-reactive protein and creatinine in the individualized group changed significantly after treatment, so were the levels of prealbumin and creatinine in the single bottle group (P<0.05). Levels of urea and pre-albumin were significantly different in the two groups after treatment. Prealbumin and retinol binding protein decreased in the single bottle group after treatment, but increased in the individualized group. C-reactive protein decreased in both groups after treatment, especially in the individualized group (P<0.05), but there was no statistically significant difference in other indexes. The rate of complications was 6.12% in the individualized group, significantly lower than 19.6% in the single bottle group (P<0.05). There was significant difference between the two groups in the duration of parenteral nutrition support [(14.66±7.15) d vs (10.41±8.22)d] (P<0.05), but not in the length of hospital stay. No related adverse reactions were reported in either group. Conclusion The individualized group has better efficacy than in the single bottle group, which can help clinicians better understand the benefits pharmacists’ involvement in parenteral nutrition therapy. The individualized parenteral nutrition support therapy helps improve clinical outcomes. References | Related Articles | Metrics

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Pharmacist-led practice in the management of elderly patients with polypharmacy ZHU Yuanchao, ZHAO Ming, HU Xin, SHI Hong 2023, 20(7): 817-821.  DOI: 10.19803/j.1672-8629.20220518 Abstract ( 83 )   PDF (1322KB) ( 115 )   Objective To clarify the importance of clinical pharmacists participating in the management of elderly polypharmacy. Methods A multidisciplinary team (MDT) management team for the elderly has been established in our hospital. On this basis, an MDT consultation system and multi-drug clinic has been set up to improve the level of treatment management. Results According to the practice of pharmacists in our hospital in the management of elderly patients with polypharmacy, we explored and established a standardized medication appropriate assessment process, outpatient admission process and prescription streamlining process for patients with polypharmacy. Conclusion The management of elderly patients with polypharmacy is an important part of geriatric pharmacy, and various methods should be taken to improve the management level of elderly patients with polypharmacy. References | Related Articles | Metrics

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Pharmaceutical care of a patient with acute pancreatitis complicated with multiple drug allergy undergoing drug stimulation test LIU Jing, XIA Liang, ZHANG Shijie 2023, 20(7): 822-824.  DOI: 10.19803/j.1672-8629.20220690 Abstract ( 87 )   PDF (1197KB) ( 91 )   Objective To explore the pharmaceutical care strategy for a patient with acute pancreatitis complicated with multidrug allergy who underwent drug stimulation test, and to provide reference for pharmaceutical care of patients with multidrug allergy. Methods A clinical pharmacist participated in the consultation for a patient with acute pancreatitis complicated with multidrug allergy, analyzed the patient’s previous allergic history, recommended the drug provocation test to justify the diagnosis of drug allergy, and suggested medications based on the patient’s condition and results of the drug provocation test. Results The patient was diagnosed with acute pancreatitis complicated with infection. The standardized skin test of β-lactam antibiotics and the drug stimulation test of cefoperazone sulbactam were negative, so cefoperazone sulbactam (3 g q8h) was selected for anti-infection treatment. No allergic reactions occurred during the treatment. The clinical pharmacist provided whole-course pharmaceutical care for this patient. Conclusion The evaluation of drug sensitivity and allergy history and drug provocation tests are critical to the selection of antibiotics in patients with multiple drug allergy. Clinical pharmacists should assist doctors in formulating treatment plans and carrying out whole-process pharmaceutical care for patients so as to ensure the safety and effectiveness of drugs. References | Related Articles | Metrics

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Axitinib tablets combined with toripalimab injection in the treatment of renal cancer-induced central retinal artery occlusion: a case report WANG Shuwei, YIN Jinjun, WANG Bing, SONG Caiping, YANG Fujun 2023, 20(7): 825-828.  DOI: 10.19803/j.1672-8629.20220552 Abstract ( 63 )   PDF (1261KB) ( 105 )   Objective To analyze the clinical characteristics, diagnosis and treatment of central retinal artery occlusion caused by axitinib combined with toripalimab in the treatment of advanced renal cell carcinoma. Methods One case of central retinal artery occlusion caused by advanced renal cell carcinoma treated with axitinib combined with toripalimab was analyzed. Results A patient with advanced renal cell carcinoma received axitinib 5 mg combined with toripalimab 240 mg, intravenous drip, once every two weeks. The overall survival (OS) was more than 5 years, and the progression-free survival (PFS) was nearly 4 years, suggesting the significant efficacy of this therapy. After 2.5 years of combined treatment, central retinal artery occlusion occurred in the right eye. No thrombosis was found by cranial enhanced MRI, chest enhanced CT or by color Doppler ultrasound of carotid and cranial vessels, lower limb arteries and veins, and renal vessels. D-dimer was 0.5 mg·L-1 (within the normal range) and ophthalmic examinations were performed to rule out other eye diseases. Toripalimab might increase the risk of thromboembolism, which was suspected of aggravating the adverse reactions of axitinib. Axitinib was discontinued, eye massage was adopted, timolol eye drops were given to reduce intraocular pressure. Lidocaine, caceanisodamine hydrochloride and dexamethasone sodium phosphate were injected retrobulbarly to alleviate spasm. Urokinase was used for thrombolysis. Methylprednisolone sodium succinate 30 mg·d-1 was given intravenously. However, these medications failed to improve the visual acuity of the right eye, but no other ocular symptoms were found during the follow-up. Conclusion Axitinib combined with toripalimab is effective for advanced renal cell carcinoma. The combined treatment requires that the clinical symptoms and imaging characteristics of patients be monitored, and clinicians should be alert to the risk of central retinal artery occlusion. References | Related Articles | Metrics

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One case of anaphylactic shock induced by fluticasone furoate LIAN Yufei, QIU Xuejia, FANG Lingzhi, ZHANG Yue, LIU Hongtao, DONG Zhanjun 2023, 20(7): 829-832.  DOI: 10.19803/j.1672-8629.20220298 Abstract ( 62 )   PDF (1330KB) ( 78 )   Objective To investigate the characteristics of anaphylactic shock induced by fluticasone furoate in order to provide reference for clinical safe and rational drug use. Methods One case of anaphylactic shock caused by the use of fluticasone furoate and treated in our hospital was analyzed. The correlations between anaphylactic shock and the suspected drug were studied using the Knoop’s adverse reaction score. The causes and mechanisms of anaphylactic shock caused by fluticasone furoate were studied by reviewing literature. Results According to the patient’s medical history, the correlation score of adverse reactions of fluticasone furoate was 5 points (possibly related). It was likely that allergic shock was caused by fluticasone furoate, or rather, by the adjuvant milk protein contained, but it was also possible that the main ingredient - umeclidinium bromide-was also involved. Conclusion Patients with a history of milk protein allergy should be routinely inquired about their allergy history, and the use of inhaled powder or other drugs containing milk protein as excipients should be avoided so as to prevent serious allergic reactions. References | Related Articles | Metrics

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One case of acute constipation induced by semaglutide injection QIN Guilan, ZHOU Muzi, JI Zhaoshuai, MAO Qiantai, AI Chao 2023, 20(7): 833-835.  DOI: 10.19803/j.1672-8629.20220584 Abstract ( 135 )   PDF (1169KB) ( 143 )   Objective To recommend measures of pharmacovigilance of semaglutide injection based on one case of acute constipation. Methods One case of acute constipation after semaglutide injection was analyzed, and a proper medication was recommended. Results The patient started with 0.5 mg semaglutide injection, but developed acute constipation symptoms the next day. After symptomatic treatment, the constipation symptoms were alleviated. After the dosage was reduced, constipation did not re-occur. Given the correlations between the patient’s clinical manifestations and the time of administration, the acute constipation was believed to have been caused by semaglutide injection. Conclusion Semaglutide injection is used for weight loss, which is off-label, so large doses may cause acute constipation. Clinicians are recommended to start with small doses according to the instructions, and inform the patients of possible adverse reactions. In case of adverse reactions, emergency medical treatment should be offered. References | Related Articles | Metrics

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Advances in risk assessment and pharmaceutical care of pregnancy medication exposure during perinatal period WANG Ran, FENG Xin, DU Boran 2023, 20(7): 836-840.  DOI: 10.19803/j.1672-8629.20220617 Abstract ( 100 )   PDF (1254KB) ( 124 )   With the changes in Chinese pregnant populations in recent years, the proportion of medication during pregnancy is relatively high, and the risk of exposure to drugs during pregnancy has also been increased. Therefore, risk assessment of drug exposure during pregnancy is critical to drug safety during pregnancy. This article reviews the current drug exposure during perinatal pregnancy, drugs and teratogenic risk, and ways to engage in risk assessment and pharmaceutical care before summarizing the problems and challenges so as to standardize the development of pharmaceutical care and provide reference for improving the risk assessment system in China. References | Related Articles | Metrics