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  • 01 August 2021 Volume 40 Issue 8
      

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  • HAN Lizhu,YIN Qinan,BIAN Yuan,HUANG Xuefei,LEI Yang,TONG Rongsheng
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    In February 2021,the International Lipid Expert Panel (ILEP) issued A Position Paper of Optimal Use of Lipid-Lowering Therapy after Acute Coronary Syndrome (ACS),which supplemented the existing guidelines on the lipids management of patients with ACS,and proposed practical solutions for the people who failed to reach the standard of lipid-lowering.The recommendation is to immediately start the combination therapy to improve access and compliance to lipid-lowering therapy of these patients.It also defines an ‘Extremely High Risk’ group of individuals after ACS,and formulates specific measures for lipid-lowering treatment for these patients.In this paper,combined with the latest 《Expert Consensus on Clinical Pathway for Blood Lipid Management in Patients With Acute Coronary Syndrome》 and 《Chinese expert consensus on lipid management of very high-risk atherosclerotic cardiovascular disease patients》,the opinion was interpreted in detail,focusing on the definition of ‘Extremely High Risk’ patients and the lipid-lowering treatment pathways of different clinical situations,in order to provide references for lipid-lowering treatment after ACS in China.

  • HU Sheng,ZHANG Xiaowen
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    Objective To study the effect of Apigenin on the proliferation,migration and apoptosis of HBBDSF in vitro,and to observe the effect of Apigenin on TGF-β1,α-SMA,Collagen I and Collagen Ⅲ protein expression levels. Methods In vitro primary culture of HBBDSF and identified,Cell Counting Kit-8 method and BeyoClick EdU Cell Proliferation Kit with Alexa Fluor 488 method to detect the effect of Apigenin on cell proliferation; The effect of Apigenin on cell migration was detected by cell scratch test. The apoptosis induced by Apigenin was detected by flow cytometry. Detection of TGF-β1,α-SMA,Collagen I and Collagen Ⅲ protein expression levels in cells after Apigenin incubation was carried out by cell immunofluorescence and Western Boltting. Results Vimentin and Keratin were positively expressed,demonstrating HBBDSF occurred in cells. The IC50 value measured by CCK-8 method was 22.75 μmol·L-1,R2=0.797. CCK-8 and EDU-488 methods showed significant inhibition of cell proliferation after Apigenin treatment (P<0.01). Cell scratch test showed Apigenin significantly inhibited cell migration (P<0.01). Apigenin can induce apoptosis (P<0.01). Celery,inhibits cell of TGF-β1,α-SMA,Collagen I and Collagen Ⅲ protein expression (P<0.05). Conclusion Apigenin can inhibit proliferation and migration of HBBDSF and induce apoptosis by inhibiting TGF-β1. At the same time in cells TGF-β1,α-SMA,Collagen I and Collagen Ⅲ protein expression level decreased.

  • ZHANG Peng,SUN Wanjin,LI Man,XU Yuting
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    Objective To explore the effect and its mechanism of salidroside on epithelial mesenchymal transition in lung adenocarcinoma cells. Methods PC9 lung adenocarcinoma cells were randomly divided into 6 groups: control group,TGF-β group,Sali 1 μg·mL-1 group,Sali 5 μg·mL-1 group,Sali 10 μg·mL-1 group,Sali 20 μg·mL-1 group.PC9 cells was treated with transforming growth factor β1 (TGF-β1) at 5 ng·mL-1 for 30 min.Then each group was intervened with salidroside of corresponding concentration for 24,48,72 h,respectively,and control group was not treated with TGF-β1 and salidroside.After the intervention,MTT test was performed at 24,48 and 72 hours after intervention in each group,and growth curve was drawn;the cell morphology was observed under the microscope,and the apoptosis rate was detected by flow cytometry.Western blotting was used to detect E-cadherin,N-cadherin,vimentin,smooth muscle actin-α (α-SMA),fibronectin (FN),and β-Catenin expression. Results The cell proliferations of Sali 5 μg·mL-1 group,Sali 10 μg·mL-1 and Sali 20 μg·mL-1 group were significantly decreased (P<0.05).Cell shape in the control group was oval or round,but most cell morphology in TGF-β1 group was spindle and connections between adjacent cells became loose.And cell morphology in Sali 5 μg·mL-1 group,Sali 10 μg·mL-1 group,and Sali 20 μg·mL-1 group were mostly oval with tight connections between the cells.The apoptosis rate of Sali 20 μg·mL-1 group was significantly higher than that in Sali 5 μg·mL-1 group and Sali 1 μg·mL-1 group.Compared with TGF-β1 group,there was no significant difference between Sali 1 g·mL-1 group (P>0.05);β-Catenin expression in Sali 5 μg·mL-1 group was significantly increased (P<0.05). Conclusion TGF-β1 can induce epithelial cells to mesenchymal cells in lung cancer cell;salidroside may inhibit EMT in lung cancer cells through the upregulation of β-catenin.

  • CHEN Xiaoyan,WU Yingqiang,ZHU Rong,ZHAO Kui
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    Objective To probe into the possible mechanisms of aspirin for the chemopreventive effects against colon cancer by investigating the effect of aspirin on the growth of human colorectal cancer cells Caco-2 and the expression of Lgr5. Methods MTT assay was used to detect the effect of aspirin on the proliferation of Caco-2 cells;The rate of cell apoptosis was analyzed by flow cytometry;The expression levels of Lgr5 mRNA in Caco-2 cells was detected by real-time reverse-transcription polymerase chain reaction (RT-PCR),respectively.The change of Lgr5 protein localization in Caco-2 cells was detected by immunohistochemistry envison method. Results Aspirin showed time and concentration-dependent antiproliferative effects on the growth of Caco-2 cells.Aspirin at the concentrations of 5.0 mmol·L-1,10.0 mmol·L-1,15.0 mmol·L-1 significantly increased the apoptosis rate in a dose and time-depending manner (P<0.05).The results of RT-PCR showed that aspirin inhibited the mRNA expressions of Lgr5 in a time-dependent manner in Caco-2 cells.There were statistical significances between the experimental groups and the control group (P <0.05).Lgr5 protein was abundantly expressed in Caco-2 cells,which was mainly located in the cytoplasm with a small number located in the cell membrane,while the nucleus was not stained.In the experimental group with 5 mmol·L-1 of aspirin,the subcellular localization of Lgr5 protein was the same as that of the control group.the localizations of Lgr5 protein subcells in 10 mmol·L-1 group and 15 mmol·L-1 group were changed.In addition to cell membrane and cytoplasmic expression,the nucleus was also expressed. Conclusion Aspirin profoundly inhibits Caco-2 cell growth and promotes apoptosis.This effect is associated with reduced mRNA expression of Lgr5 and the affected localization of Lgr5 protein,which may be one of the potential mechanisms of aspirin for the chemoprevention of colorectal cancer.

  • YI Jiadai,CHANG Xiangyun,WANG Xiaoli,CHENG Yunjie
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    Objective Through the intervention of probiotics (VSL#3) on obese mice induced by high fat diet,the expression levels of diacylglycerol (DAG),protein kinase C (PKC) and glycolipid metabolism indexes in liver tissue were observed,and the effect of probiotics on insulin resistance and its possible mechanism were explored. Methods Sixty male mice were fed with high-fat diet (HFD,30 mice) and normal diet (NFD,30 mice) for 8 weeks,respectively,and then were weighed to evaluate the modeling results of the obese mice.The obese mice and NFD group were randomly divided into three groups: active VSL#3,inactivated VSL#3 and blank control (distilled water of the same volume) for 4 weeks.After the feeding,the levels of WT,FBG,FINS,TG,TC,HOMA-IR,DAG,and PKC were measured,respectively.The correlation between the expression levels of DAG and PCK,HOMA-IR,and other metabolic indexes was analyzed. Results ① Compared with NFD blank control group,WT,TC,TG,FBG,FINS and HOMA-IR levels in HFD blank control group increased (P<0.05).② The expression of DAG and PKC in liver tissues of HFD blank control mice increased (P<0.05).③ The correlation analysis showed that the increase of DAG and PKC was positively correlated with HOMA-IR.④ The levels of WT,TC,TG,FBG,FINS,HOMA-IR,and the expression of DAG and PKC in liver of VSL#3+HFD group were lower than those of inactivated VSL#3+HFD group and HFD blank control group (P<0.05). Conclusion ① High fat diet can increase insulin resistance,blood lipid level,and DAG-PKC pathway expression in mice.② DAG-PKC pathway expression has a positive correlation with IR.③ Probiotics can improve insulin resistance in obese mice,which may be related to DAG-PKC pathway.

  • XIANG Xiaoyan,YU Zhongshu,XIE Jiaxi,SHI Yutao,ZHANG Jingqing,ZHAO Hua
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    Objective To study the pharmacokinetic characteristics of evodiamine (ED) and chitosan hybrid evodiamine composite nanoparticles (CENP) in rats,and to compare their bioavailability and bioequivalence. Methods In this study,12 healthy male rats were randomly devided into two groups,then ED and CENP were intragastrically administrated.Blood samples were taken within 96 h after the administration and the plasma concentration of ED was measured by HPLC.Then the DAS 2.1.1 software was used to calculate the main pharmacokinetic parameters and analyze their bioequivalence. Results When compared to ED,AUC(0-∞) and Cmax of CENP increased by about 3.57 and 1.92 times,respectively.MRT (0-96 h) of CENP was extended by about 7.59 h.There was a significant difference in the tmax between CENP and ED.The AUC (0-∞),Cmax of CENP,and ED were not within the standard range. Conclusion Compared to ED,CENP possessed a higher oral bioavailability.Furthermore,CENP and ED were not bioequivalent.

  • SA Rihu,WU Liji,XIE Xiuhua,SA Chula
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    Objective To study the serum pharmacokinetics of sugmel-3 water extracted piperine from Mongolian medicine. Methods Serum samples were pretreated with acetonitrile to precipitate protein,and the content of piperine in serum was determined by UPLC-Q-TOF method with verapamil hydrochloride as an internal standard.The column was ACQUITY UPLC HSS T3 C18 (2.1 mm×100 mm,1.8 μm).The mobile phase was mathanol (A)-0.1% formic acid water (B),A:B=70%:30%;flow rate: 0.4 mL·min-1;Column temperature was set at 30 ℃;injection volumn was 2 μL.Electrospray ionization ion source (ESI) was used to detect the ions as positive ions mode by multi-reaction ion monitoring.M/Z piperine 286/201 and verapamil 455/165 were selected,respectively. Results The linear relationship of piperine was good in the range of 0.025-20.272 μg·mL-1 (R2=0.999 4).The intra-day precision RSD was 1.2%-8.1%,and day time precision RSD was 1.7%-12.7%.Recovery rate of extract was 70%~85%.After oral administration of SD rats at the dose of 3.96 g·kg-1,main pharmacokinetic parameters were that Cmax was 0.415 μg· mL-1,and tmax was 4.00 h,and t1/2 was 10.10 h·pg·mL-1;AUC0~24was 3.36 h· pg· mL-1;AUC0~∞ was 4.17 h· pg· mL-1; MRT was 14.10 h. Conclusion The established method is fast,accurate,and is applicable for study on pharmacokinetics of piperine in rats.

  • ZHOU Fan,SONG Jian,YU Airong
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    The low positive rate of cerebrospinal fluid culture,the influence of blood-brain barrier on drug permeability,and the increased incidence of intracranial infection caused by multi drug-resistant bacteria after neurosurgery significantly increase the difficulty of treatment.In the treatment of postoperative intracranial infection,the timely and reasonable application of antibacterial drugs is the key link.In this paper,combined with domestic and foreign guidelines,expert consensus,and related researches in recent years,we reviewed the research progress of pathogenic bacteria changing trend,empirical selection of antibiotics,targeted treatment,the course of antibiotics use,and so on,so as to provide references for the clinical rational use of antibacterial drugs.

  • LIU Yuqing,YANG Yong,CUI Xiaojiao,ZHANG Jing,LI Qinhui,YU Feng
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    Objective To evaluate the effect of "Tripartite system (medical treatment,medicine and medical insurance) reform" management mode on the management of carbapenems and tigecycline antibiotics in Sichuan Provincial People’s Hospital,and to provide a reference for the management of antibiotics usage. Methods A "tripartite system" joint management mode with the participation of Pharmacy Department,Medical Insurance Office,Medical Department and other related departents was established.Data of the use of carbapenems and tigecycline from discharged patients were collected from April to July 2020 (before the implementation of "tripartite system" joint management mode) and from August to November 2020 (after the implementation of "tripartite system" joint management mode) in Sichuan Provincial People’s Hospital.Data,in terms of usage,cost,medical insurance violations,and unreasonable prescriptions,were analyzed and compared. Results The usage rates of carbapenems and tigecycline were significantly decreased from 2.65% before the management to 2.42% after the management (P<0.05).And the proportion of carbapenems and tigecycline in the use of antimicrobial agents also decreased significantly from 5.08% to 4.69% (P<0.05).In addition,defined daily doses (DDDs),antibiotics use density (AUD) and per capita cost of carbapenems and tigecycline decreased from 11 020.75,2.36 and 7 105.22 yuan to 9 877.00,1.96 and 6 923.44 yuan,respectively.The costs of carbapenems and tigecycline as a proportion of total drug cost and total treatment cost were decreased from 17.89%,7.39% to 17.08%,7.11%,respectively.The ratio of the violation in medical insurance preliminary audit and second audit of carbapenems and tigecycline decreased significantly from 7.34%,0.57% to 3.02%,0.00%,respectively (P<0.05).Meanwhile,the total amount of hospital deduction decreased significantly from 29 956.96 yuan to 0 yuan.After the management with the significant increase of prescription comment rate from 61.01% to 81.50% (P<0.05),the rate of unreasonable prescriptions decreased significantly from 7.94% to 0.41% (P<0.05). Conclusion A new management mode for antibiotics was successfully established,and the idea of "tripartite system" was applied to the management of antibiotics for the first time,which promoting the rational use of carbapenems and tegacycline.At the same time,the management mode reduced the economic burden of patients and medical insurance,improved the situation of non-payment of medical insurance,but it still needs to be further improved.

  • LENG Bing,ZHANG Wen,ZHANG Li,YAN Genquan,DUAN Xiaoju
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    Numerous studies have showed that aerosolized polymyxin in the treatment of pneumonia has good targeting,significant curative effect and low nephrotoxicity.Several guidelines currently recommended that patients suffering from pneumonia caused by multidrug-resistant gram-negative bacteria (MDR-GNB) should receive aerosolized polymyxin as one of the important therapy regimens.Based on current literatures,the relevant data of this treatment method mainly come from the clinical practice of colistin methanesulfonate (CMS),while polymyxin B sulfate (PMBS) is related due to the relative limitation of the application area,thus leading to the less research available.Findings from current research suggest that compared with inhaled CMS,inhaled PMBS has shown faster and better efficacy in the treatment of pneumonia.Nevertheless,it is worthy of note that safety issues are yet to be fully elucidated.However,sufficient data are still lacking to support the specific clinical application of polymyxin in the treatment of pneumonia,especially in terms of drug formulation and dosage.Therefore,future researches are needed and the evaluation of safety and effectiveness of aerosolized polymyxin could be considered in the treatment of pneumonia,especially with the accurate and reliable PK/PD data to guide its clinical application.

  • CAO Pei,YANG Yong,ZHANG Zhiyong
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    Objective To explore risk factors for mortality and antimicrobial therapy of bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods In the retrospective study,patients with bloodstream infections (BSIs) caused by CRKP,who were hospitalized in a Tier III hospital in Sichuan from January 2016 to December 2019,were assigned to survival or death groups according to the 30-day prognosis.The risk factors of death were analyzed,and the differences between the combination group and the single drug group were compared. Results There were 48 patients with BSIs caused by CRKP.ICU was the largest source of the cases (n=27,56.3%),followed by Hematology department (n=10,20.8%).A total of 36 nonduplicate CRKP blood isolates were enrolled in this study with a 30-day mortality rate of 52.8% (19/36).In a logistic regression analysis,30-day mortality was independently associated with multiple organ dysfunction syndrome (P<0.05).The 30-day mortality rate of the patients (n=29) treated with antimicrobial combination therapy was similar to those (n=7) receiving monotherapy (P>0.05).Four patients who received prolonged-infusion regimen of a carbapenem survived,and 3 of them received combination therapy of tigecycline and carbapenem. Conclusion CRKP BSIs are associated with high mortality.A 30-day mortality rate was independently associated with multiple organ dysfunction syndrome.To improve survival rate,prolonged-infusion regimen of carbapenems may be more effective.

  • LONG Shanshan,HUANG Xiangning,ZHANG Jie,ZHONG Min,LIU Aibo,YU Hua
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    Objective To analyze the distribution and drug resistance of pathogens isolated from bloodstream infections in patients of the member units of Sichuan bacterial resistance monitoring network from 2016 to 2020,and to provide the basis for the rational use of drugs in medical institutions in our province. Methods Non-repetitive pathogens isolated from clinical blood samples of inpatients and outpatients from 86 member units with qualified data from 2016 to 2020 were obtained from the Sichuan Province Antimicrobial Resistance Surveillance System.Identification and antimicrobial susceptibility analysis were carried out by Vitek2 Compact and standard disc diffusion method,and the results were determined according to the CLSI 2020 with data analyzed with WHONET 5.6 software. Results Total 84 232 pathogenic bacteria were isolated from the blood samples,including 49 523 Gram-negative bacteria (58.8%) and 34 709 Gram-positive bacteria (41.2%).The top five most frequently isolated pathogens were Escherichia coli (33.9%),Klebsiella pneumoniae (11.0%),Staphylococcus epidermis (9.3%),Staphylococcus aureus (6.8%),and Staphylococcus hominis (6.5%).Escherichia coli and Klebsiella pneumoniae were still highly sensitive to carbapenems,and the resistance rate was less than 7.3%.The resistant rates of Escherichia coli and Klebsiella pneumoniae to carbapenems were 1.0% and 5.9%,respectively.The detection rates of methicillin-resistant in Staphylococcus aureus and in coagulase-negative Staphylococcus aureus were 25.5% and 71.7%,respectively,and MRSA and MRCNS were highly resistant to common antibiotics than methicillin-sensitive strains (MSSA and MSCNS),and resistant strains to vancomycin and linezolid were not isolated.The two most frequently isolated Enterococcus were Enterococcus faecium and Enterococcus faecalis,and resistance rate to vancomycin and linezolid were decreasing every year. Conclusion The pathogens isolated from blood were diverse,and Gram-negative bacteria were the main pathogens of BSI.Antimicrobial therapy should be prescribed according to the drug sensitivity results,and should be used more rationally to obtain a better effect.

  • ZHOU Tao,GONG Weijing,CAI Xuefeng,ZENG Fang,ZHANG Yu
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    Objective To explore the clinical efficacy of mucinous lytic expectorants in patients hospitalized with severe COVID-19. Methods Severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between February 1,2020 and March 10,2020 were enrolled in the retrospective study.Patients were divided into two groups based on the use of mucinous lytic expectorants.The primary endpoint was the clinical improvement time assessed on a seven-category ordinal scale.The secondary endpoints included mortality and time to negative conversion using throat swab SARS-CoV-2 nucleic acid test. Results Total 127 patients were treated with mucinous lytic expectorants while 81 were not.There were no significant differences between two group in demographic characteristics,laboratory test results,and distribution of ordinal scale scores at enrollment.Treatment with mucinous lytic expectorants was not associated with a difference in the time to clinical improvement (P=0.129) and the accumulative rate of clinical improvement (P=0.7557,HR=0.949,95% CI=0.683-1.318).There were also no significant differences in the time to throat swab SAR-CoV-2 nucleic acid negative conversion and mortality. Conclusion In hospitalized adult patients with severe COVID-19,no significant benefit was observed with mucinous lytic expectorants treatment.

  • HAN Xia,LIU Zhelong
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    Objective To explore the effect of selenium yeast tablets on Hashimoto's thyroiditis patients with normal thyroid function in the real world. Methods A total of 187 Hashimoto's thyroiditis patients with normal thyroid function were treated with selenium yeast tablets and followed up for 6 months.The changes in thyroid peroxidase antibody (TPOAb),thyroglobulin antibody (TgAb),thyroid stimulating hormone (TSH),free triiodothyronine (FT3),and free thyroxine (FT4) before and after treatment were retrospectively analyzed.The patients were divided into groups according to the changes in thyroid antibodies after treatment,and the differences among various factors such as age,gender,the course of disease,daily dose of selenium,and levels of baseline antibody were compared. Results After the treatment with selenium yeast tablets,the levels of TPOAb and TgAb decreased significantly after 3 months of treatment and after 6 months of treatment (P<0.05),but the levels of TSH,FT3,and FT4 showed no significant changes after 6 months of treatment (P>0.05).The decreased amplitude of TPOAb was significantly higher than that of TgAb (P<0.05).There was no significant difference in the percentage of the decreases of TPOAb and TgAb between the first 3 months of treatment and the following 3 months of treatment (P>0.05).There was no significant differences in age,sex,course of disease,daily selenium dosage,and levels of baseline antibody between people whose TPOAb decreased after selenium yeast treatment and those whose TPOAb did not decrease (P>0.05).Compared with the patients whose TgAb decreased after treatment,the patients whose TgAb did not decrease after treatment had a larger mean age,a higher proportion of female patients,and a lower mean baseline concentration of TgAb (P<0.05).There was no significant difference in the changes of both TPOAb and TgAb between the groups treated by different selenium dosage (P>0.05). Conclusion Selenium yeast tablets treatment may reduce the levels of thyroid antibodies and improve the immune response in patients with Hashimoto's thyroiditis.

  • ZHANG Shanshan,WANG Yuehua,DU Guanhua
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    High mobility group box 1 protein (HMGB1) is a highly conserved chromosome binding protein,which mainly exists in the nucleus of eukaryotic cells and participates in the process of gene replication,transcription and repair.It can also be released by immunocompetent cells and necrotic cells.By activating RAGE and toll like receptor 2/4,it can cause inflammatory reaction.A large number of studies have shown that the HMGB1 inflammatory signaling pathway is involved in the pathological process of neurological diseases such as brain edema,cerebral ischemia-reperfusion,neurodegenerative diseases,and depression.Therefore,inhibition of HMGB1 and activation of related signaling pathway might be an important strategy for the treatment of inflammatory diseases in the central nervous system.In this review,the neuroinflammatory response of HMGB1 and the research status of HMGB1 inhibitors were described,providing a reference for the research and development of HMGB1 inhibitors for the treatment of neuropsychiatric diseases.

  • CHENG Sijin,ZHANG Chengliang
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    In recent years,there are lots of studies on baicalin in liver diseases.Baicalin was used to adjuvant treatment of acute hepatitis,chronic hepatitis and persistent hepatitis.This review will focus on the pharmacological effects of baicalin on fatty liver disease,such as anti-oxidant effects,inhibiting lipogenesis,improve insulin resistance,upregulate angiopotietin like proteins 6 and anti-inflammation effect,etc.

  • XU Huimei,YANG Yifan,CHENG Long,MA Xueni,ZHANG Dekui
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    Helicobacter pylori (Hp) is closely related to the occurrence and progression of a variety of gastrointestinal and parenteral diseases.Several influential consensuses in China and abroad recommend that indications for Hp eradication can be extended to asymptomatic patients.However,the increase in the resistance rate of commonly used antibacterial drugs is the main reason for the decline in the eradication rate in recent years.Therefore,we urgently need to search new regimens with more effectiveness and safety for Hp infection.Sitafloxacin is a new type of the fourth-generation quinolone drug approved by Japan in 2008.Currently,it has only entered clinical practice in Japan and Thailand.Compared with other fluoroquinolone antibacterial drugs,sitafloxacin has a broader antibacterial spectrum,rapid onset,low minimal inhibitory concentration and drug resistance rate,few adverse events,even with efficacy for Hp strains containing the gyrA mutation.Several clinical trials have shown that sitafloxacin combined with other antibiotics,proton pump inhibitor (PPI) or vonoprazan,can be recommended as a remedy for Hp infection.

  • XIAO Ying,WU Meijuan,GUO Yuanlin
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    Objective To optimize the formula of cefprozil dry suspension of the dosage of citric acid,sodium citrate and microcrystalline cellulose-carboxymethyl cellulose sodium,and to control the specific impurities in the prescription to meet the requirements. Methods The dosage of citric acid,sodium citrate and microcrystalline cellulose carboxymethylcellulose were used as factors,and the unknown maximum amount of single impurity in cefprozil dry suspension was set as the response value.The Box-Behnken response surface methodology was used to optimize the formulation. Results The optimal dosage of citric acid,sodium citrate,microcrystalline cellulose carboxymethylcellulose in a single dose were as follows: 16.89 mg,27.67 mg,and 23.78 mg,respectively. Conclusion Box-Behnken response surface method can be used to optimize the formulation of cefprozil dry suspension.The established fitting model is simple with good predictability.

  • WANG Xue,ZHANG Baoxi,XING Cheng,GONG Ningbo,LYU Yang
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    Objective New crystal form of nimodipine was prepared.The formation mechanism of the three crystal forms of nimodipine and the differences in the intermolecular interaction were studied. Methods The new crystal form of nimodipine (C) was prepared by solvent evaporation.The structure was obtained through the single crystal X-ray diffraction (SXRD) and the intermolecular interaction was analyzed by Hirshfeld surface method. Results The form C of nimodipine was formed in 1:1 ratio of nimodipine and DMSO.According to the reported single crystal data,the crystal A and B are solvent-free nimodipine molecules with different configurations.These three crystal forms have similar molecular interactions.The three interactions of H…H,H.…O,and H…C account for more than 90% of the total forces,and the magnitudes of the three forces are different. Conclusion Nimodipine contains dihydropyridine ring.As the main hydrogen bond donor,NH forms hydrogen bond with O atom,which becomes the main force in nimodipine crystal molecule.The interaction between molecules can be clearly revealed by Hirshfeld surface analysis method.

  • ZHU Xiali,LI Linghua,WANG Shasha,WANG Baiyan,GUAN Yanbin,JIA Yongyan
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    Objective Using hydrophilic nano copper sulfide (PVP/CuS) as a photosensitizer,glycyrrhetinic acid (GA) as a tumor targeting molecule,docetaxel (DTX) as a model drug,a near-infrared light responsive active targeting liposomes (GA-DTX-PVP/CuS-Lip) was prepared,and its physical chemical properties and in vitro antitumor activity were also studied. Methods The thin film dispersion method was used to prepare GA-DTX-PVP/CuS-Lip,and its microstructure was observed under transmission electron microscope.The particle size and zeta potential were measured by laser granulometer.The encapsulation efficiency and drug loading ratio were determined using ultrafiltration and centrifugation method.Combined with 808 nm laser irradiation,the light-thermal conversion experiment was carried out.The in vitro drug release test was carried out by using the dialysis method at 37 ℃ and 45 ℃.The in vitro antitumor activity of GA-DTX-PVP/CuS-Lip against SMMC-7721 cells with or without 808 nm laser irradiation was also measured. Results GA-DTX-PVP/CuS-Lip was observed to be spherical with uniform size under TEM.The particle size and Zeta potential were (226.73±0.17) nm and (-4.05±0.57) mV,respectively.The encapsulation efficiency and drug loading ratio were (96.33±0.21) % and (6.63±0.39) %,respectively.GA-DTX-PVP/CuS-Lip had a significant photothermal conversion effect under laser irradiation at 808 nm in a concentration and time-dependent manner.The drug release test showed that compared with DTX solution,GA-DTX-PVP/CuS-Lip had sustained and temperature-dependent release characteristics,and the release rate at 45 ℃ was significantly higher than that at 37 ℃.GA-DTX-PVP/CuS-Lip had higher inhibitory effect on SMMC-7721 cells when combined with 808 nm laser irridation. Conclusion The preparation process of GA-DTX-PVP/CuS-Lip is stable and feasible,which can provide a theoretical basis for further tumor photothermal therapy.

  • DU Zhuo,YE Quanying,LIN Jiecheng,KUANG Cuiqiong,MO Yufang,YU Xiaoyao,LI Haiyi,GUO Jialiang
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    Objective The preparation process parameters and quality estimation of eugenol dropping pill were investigated to screen for the best preparation condition and to prepare the eugenol dropping pills that meet the requirements of the Chinese Pharmacopoeia 2015. Methods The L9(34) orthogonal design test method was used to screen the prescription and prepare the dropping pill.And the method for quality determination of eugenol dripping pills was established. Results The optimal prescription for preparing eugenol dropping pill is: The percentage of drugs in total mass was 2.5%,the temperature of the drug solution was 80 ℃,the dropping distance of the condensate was 18 cm,and the dropping distance of the drug solution was 6 cm.The results showed that the prepared dropping pills had good roundness,moderate hardness,and the mass difference meets the Chinese Pharmacopoeia’s standard. Conclusion The eugenol anti-coronary heart disease dropping pills prepared in the experiment have good appearance,suitable hardness,and the mass difference of dropping pills are in accordance with the requirements of Chinese Pharmacopoeia 2015.

  • LI Honglian,ZHANG Jun,LIU Ruming,YAO Qin,LI Qian,HUANG Hua,WANG Jingjing,LU Shanshan
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    Objective To evaluate the efficacy and safety of the combination of thiopurines with 5-aminosalicylates versus thiopurines for inflammatory bowel disease. Methods The Cochane Library,PubMed,FMRS,CBM,WangFang Data,VIP and CNKI were searched online from the establishment dates of the databases to October 2019 to collect relevent studies.RevMan 5.3 and Stata 12.0 software were used to perform meta-analysis after selected literatures.Two independent reviewers extracted data and evaluated the risk of deviation of the included studies. Results A total of 12 studies were included with a total of 3751 patients.Meta-analysis results showed that AZA/6-MP+5-ASA group had a higher level of 6-TGN[MD=24.45,95%CI(48.63,-40.28)%,P<0.05],and there were no significant difference in 6-MMP level (P>0.05).For safety,AZA/6-MP+5-ASA group had a lower rate of overall adverse reactions[OR=1.78,95%CI (1.03,3.08)%,I2=63%,P<0.05]. Conclusion The current evidence shows that the combination of thiopurines with 5-aminosalicylates have a better effect and lower adverse reaction incidences than thiopurines alone.

  • CHONG Xin,CHU Yanqi
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    Objective To summarize the clinical pharmacists' participation in the process of adjusting the treatment plan of a patient of severe acute pancreatitis with hyperrenal function,so as to provide a reference for promoting the clinical safety and rational use of drugs. Methods For a patient of acute severe pancreatitis,the clinical pharmacist participated in the formulation of anti-infection treatment plan,analyzed the medication situation of the patient,and suggested and adjusted the treatment plan Results After adjusting the medication regimen,the patient's body temperature returned to normal. Conclusion Clinical pharmacists should carry out whole-process pharmaceutical care for the anti-infection treatment and timely adjust the medication regimen for patients with hyperrenal function,so as to promote clinical rational medication and ensure the drug safety for patients.

  • JIANG Xiaolei,ZHU Yulian,LI Jing,QIAN Mengru,CUI Xiaojiao,DONG Lie,YANG Yong
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    Objective To provide empirical reference for the clinical diagnosis and treatment of drug hypersensitivity syndrome (DIHS) induced by anti-tuberculosis drugs. Methods A case of DIHS caused by anti-tuberculosis drugs was reviewed,and combined with the expert consensus of DIHS and relevant literature,the clinical symptoms,laboratory indicators,and the treatment of the patient were analyzed. Results The patient presented a persistent fever,delayed rash,multiple enlarged lymph nodes,hematological abnormality,liver injury,and relapse,which met the diagnostic criteria of DIHS. Conclusion Timely discontinuation of anti-tuberculosis drugs is the key.Mild patients can use anti-allergic drugs for the symptomatic treatment,and severe patients can use glucocorticoid and immunoglobulin impulse therapy.Hormone treatment may cause the spread of tuberculosis,but there is no consensus.Thus,we should weigh the advantages and disadvantages.

  • SUN Hao,YANG Zhenyu,ZHAO Limei
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    Objective Clinical pharmacists participate in individualized drug therapy to provide references for clinical use of cyclosporine. Methods A patient who received anti-rejection therapy with cyclosporine for a long time after allogeneic hematopoietic stem cell transplantation was studied.During the treatment of cyclosporine,the blood concentration of cyclosporine fluctuated abnormally with omeprazole and voriconazole,which potentially affected the efficacy of cyclosporine.A series of adverse reactions such as abnormal liver and kidney function index were induced. Results Through the analysis of the factors affecting the blood concentration of cyclosporine and the means of monitoring the blood concentration,the clinical pharmacists optimized the dosage of cyclosporine and the individualized medication was achieved. Conclusion Drug interaction in the drug combination with cyclosporine should be considered cautiously,and an individualized drug administration scheme should be developed to ensure the safety and effectiveness of medication for patients.

  • LI Na,LIU Nan,ZHANG Ailing,SHI Chengcheng
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    Objective To analyzed a case of carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia after lung transplantation and discussed the choice of anti-infective drugs for CRKP,in order to provide a reference for clinical anti-infective treatment of CRKP. Methods Clinical pharmacists participated in the course of anti-infective treatment of patients after lung transplantation.The characteristics of carbapenems,tigecycline,polymyxin B,and ceftazidime-avibactam which were commonly used in the treatment of CRKP infection were analyzed.Pharmaceutical services were provided in terms of drug selection,dosage and treatment optimization in order to help clinicians formulate optimal anti-infective regimen. Results In the treatment of CRKP infection,two or three drugs are commonly used in combination.Carbapenems can be considered as a combination drug when MIC is equal or less than 8 mg·L-1.Carbapenems are not recommended when MIC is more than 8 mg·L-1 (MIC can be increased to 16-32 mg·L-1 when polymyxin is combined).When tigecycline is used in the treatment of pneumonia,in order to increase its concentration in lungs,200 mg of the loading dose and 100 mg q12h of the maintenance dose can be given.In order to make polymyxin B reach an effective steady-state plasma concentration as soon as possible,the loading dose of polymyxin B should be 2.0-2.5 mg·kg-1,and the maintenance dose should be 1.25-1.5 mg·kg-1 every 12 hours.Ceftazidime-avibactam is a new effective drug for the treatment of CRKP infection and the recommended dose is 2.5 g q8h.By optimizing the treatment plan,the infection was effectively controlled,and the clinical symptoms improved.The etiological results turned negative with no recurrence occurred. Conclusion Clinical pharmacists bring their specialty into a full play.Combined with the patient's condition,clinical pharmacists work out anti-infective treatment programs with doctors,which is conducive to ensure patients' safe,rational and effective use of drugs,and reflect the value of clinical pharmacists.

  • BAI Xuefei,RAN Yiwen,ZHAO Yinyu,ZHAO Jinxia,CHEN Li
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    Objective To analyze and compare the adverse event information of proton pump inhibitors (PPIs) based on the FAERS database,and to explore the potential adverse events signals in order to optimize the treatment plan for patients and provide a reference basis for clinical safe and rational drug use. Methods A total of 24 quarters of adverse events report data from the first quarter of 2015 to the fourth quarter of 2020 are extracted from FAERS.Data mining is performed on the PPIs report using the odds ratio (ROR) and medicines and healthcare products regulatory agency (MHRA) method.After obtaining the effective signals,the term set of MedDRA is used for translation and systematic classification. Results After the secondary screening,the results showed that omeprazole involved 23 organ system classifications (SOC) with a total of 540 signals.Pantoprazole involved 23 SOC with a total of 340 signals.Esomeprazole involved 22 ROC with a total of 239 signals.Lansoprazole involved 22 ROC with a total of 298 signals. Conclusion The common ADR signals and the involved systems obtained in this study are consistent with the instructions,which proves the reliability of this study.There are certain differences among the ADR of 4 PPIs,which can provide a reference for clinical drug use and promote rational drug use.

  • WU Wei,NIAN Honglei,LI Tianzuo
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    Objective To study the common problems and differences in the writing of informed consent texts in clinical trials of different types of drugs,and to provide suggestions on the writing of informed consent forms for drug clinical trials. Methods A retrospective analysis of the ethical review opinions of the ethics committee of all drug clinical trial informed consents of a third-class hospital in Beijing from 2018 to 2019 was carried out,and the common problems were compared in different drug clinical stages and different capital biddings. Results In a total of 41 copies of informed consent for clinical trials,the passing rate of preliminary reviews was only 9.76%.Five types of focus problems were found in the informed text that needs to be revised.The "available compensation and treatment" problem is the most frequent issue,and it occurs more frequently in phase II-IV stages of clinical trials,and has different manifestations in different capitals sponsors;As for the "data use and confidentiality" issue,the frequency is the lowest among the five focus problems,while almost all of those problems occured in foreign sponsors;the remaining three types of problems have no significant differences among different clinical trial stages or different capital sponsors. Conclusion The most common problems in writing informed consent texts for clinical trials of different capitals and different types of drugs are slightly different,while researchers should therefore pay more attention to laws and regulations to ensure the text of informed consent.In addition,ensuring the modern legal and regulatory connotations of the words used in the informed consent text,reflecting the logical connotation of the three elements of "information,comprehension,and voluntariness" and the value connotation of "subject-centered"are the basis for writing informed consent.

  • LI Feie,LI Juan,LIU Dong
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    In order to ensure the rational administration of medicine for athletes during large-scale games,the whole process management of doping drugs in designated hospitals was discussed according to the relevant laws and standards,including regulations,catalogues,information systems,training and administration,etc.Being familiar with the pharmacological knowledge and rules of doping drugs,pharmacists should take part in the management of doping drug to distinguish accurately on the prohibition of specific gender or drug dosage and doping drugs hidden in traditional Chinese medicine,etc.,so as to help hospital personnel improve professional knowledge of doping drug and make precise management of the safe medication for athletes.