Objective To investigate the effect of XMD17-109 on the viability of glioma cells and its molecular mechanism based on extracellular signal-regulated kinase 5(ERK5)/inositol 1,4,5-trisphosphate receptor-interacting protein(ITPRIP)signaling pathway.Methods U251 glioma cells were routinely cul-tured,and ERK5 activity was inhibited by XMD17-109.ERK5 knockdown and ERK5 overexpression models were constructed by transfection of RNA fragments and plasmids,respectively.Cells were divided divided into the XMD17-109 group,the Control group,the siERK5 group,the siNC group,siERK5-OE group,the Vector group,the ERK5-OE+XMD17-109 group and the Vector+XMD17-109 group.The cell viability was detected by CCK-8,scratch and flow cytometry experiments and so on.The mRNA and protein expression levels of ERK5 and ITPRIP were detected by reverse transcription-quantitative real time PCR(RT-qPCR)and West-ern blot.Results Compared with the Control group,the cell viability of the XMD17-109 group decreased,and the expression level of ITPRIP decreased(P＜0.05).Compared with the siNC group,the cell viability of the siERK5 group was decreased,and the expression level of ITPRIP was decreased(P＜0.05).Compared with the Vector group,the cell viability of the ERK5-OE group was enhanced,and the expression level of ITPRIP was increased(P＜0.05).Compared the with Vector+XMD17-109 group,the cell viability of the ERK5-OE+XMD17-109 group was enhanced,and the expression level of ITPRIP was increased(P＜0.05).Conclusion XMD17-109 can inhibit the viability of glioma cells by inhibiting ERK5/ITPRIP signaling pathway,which is expected to be a potential drug for glioma treatment.

Antiplatelet drugs are the cornerstone of long-term treatment and secondary prevention for ischemic stroke/transient ischemic attack (TIA) recommended by guidelines, aimed at reducing the risk of recurrent stroke and other cardiovascular events. However, some patients with ischemic stroke/TIA may still experience ischemic events during antiplatelet therapy, known as high on-treatment platelet reactivity (HTPR), which typically occurs in patients taking aspirin or clopidogrel. This article elaborates the incidence, risk factors, and commonly used evaluation methods of HTPR in patients with ischemic stroke/TIA, and elucidates the clinical significance of HTPR in patients with ischemic stroke/TIA, and investigates the antiplatelet treatment protocol of patients with HTPR.

OBJECTIVE To estab lish the pre paration method of clopidogrel active thiol metabolite （CATM），and to provide reference for the synthesis of cis-CATM. METHODS CATM was prepared ，separated and purified with isolated rat liver perfusion and ChromCore 120 C18 preparative column ，using（S）-2-oxo-clopidogrel as substrate. The target compounds were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. The retention time of the active configuration of CATM in the human body （cis-CATM）were compared to confirm the proportion of active configuration in the target product. RESULTS The conversion rate of the target product was 11.71％. The target products were identified as CATM by MS and 1H-NMR. Peak 2-peak 5 of CATM were four stereoisomers. The retention time of them were 21.3，22.3，26.5，27.3 min. The peak area ratios of them were 7.13％，7.23％，63.52％，14.97％，respectively. Based on that retention time of the active configuration of CATM in human body was 26.3 min，the active cis-stereoisomer in the target product CATM accounted for 63.52％. CONCLUSIONS This method is low-cost ，simple，and can prepare CATM with higher active configuration.

Clopidogrel is the most commonly used antiplatelet agent for acute coronary syndrome, ischemic stroke, and before and after percutaneous coronary intervention, and endovascular treatment of large vessel occlusive stroke, but there are individual differences in antiplatelet effect, that is, clopidogrel resistance (CR). CR is usually attributed to the decrease of the concentration of sulfhydryl metabolites in plasma, and there are many factors that cause the decrease of the concentration of sulfhydryl metabolites. This article reviews the research progress of CR-related risk factors, so that clinicians can assess the risk of CR and adopt individualized antiplatelet therapy to improve the clinical outcome of patients.

OBJECTIVE：To analyze the situation of inpatients with heart failure taking sacubitril-valsartan. METHODS ：The data of heart failture inpatients using sacubitril-valsartan in our hospital were collected during Oct. 2019 to Mar. 2020，including basic information of patients such as gender ，age，inpatient department ，length of stay ；the application of sacubitril-valsartan ， including indications ，contraindications，usage and dosage ，course of medication ；conversion with angiotensin converting enzyme inhibitor（ACEI）/angiotensin Ⅱ receptor antagonist （ARB）and adverse drug reactions ，were summarized. RESULTS ：A total of 252 cases were collected ，including 172 males（68.25％）and 80 females（31.75％）. The average age of the patients was （67.02± 14.23）years old ，and 85 cases were 75 years or older （33.73％）. Average hospitalization time was （12.03±8.19）d，the average left ventricular ejection fraction （LVEF）before medication was （38.69±10.45）％，the average blood potassium was （4.16±0.65） mmol/L，and the average estimated value of glomerular filtration （eGFR）was（69.14±32.01）mL/（min·1.73 m2）. The main distri- bution departments were cardiology department （59.14％），followed by nephrology department （8.73％），respiration department （7.14％），cardiac surgery department （5.95％），geriatrics department （5.56％），emergency medicine department （3.57％）and neurology department （3.17％）. All patients had indications ，but 25 cases（9.92％）had contraindications ，6 cases（2.38％）had blood potassium ＞5.4 mmol/L，19 cases（7.54％）had eGFR ＜15 mL/（min·1.73 m2）. The usage and dosage was 50 mg/bid （45.24％）；39 cases（15.47％）were given medicine once a day ，which was unreasonable. Average treatment course was （7.80± 5.86）d. 7 patients（2.78％）converted to ACEI ，and 3 patients（42.86％）had a conversion interval less than 36 h；20 patients （7.93％） were converted to ARB ，and there was no obvious inappropriate conversion. Hypotension occurred in 14 patients （5.56％）. Blood pressure returned to the normal range in 2 patients after drug withdrawal and 12 patients after dose reduction. No patient had adverse reactions such as involuntary muscle tremor and arrhythmia. CONCLUSIONS ： All the inpatients wit h heart failure in our hospital have indications and good safety. Only a few patients have blood pressure intolerance. However ，there were problems such as low dosage ，inappropriate frequency of administration ，drug use against contraindications，and inappropriate timing of drug conversion. Clinical pharmacists can carry out the knowledge propaganda of rational drug use ，strengthen the pharmaceutical care of patients ，timely detect the situation of irrational drug use and monitor adverse drug reactions ，and actively intervene to ensure the rationality and safety of patients ’medication.

OBJECTIVE:To investigate the in vitro dissolution behavior and in vivo pharmacokinetics of Cinacalcet hydrochloride tablets, and to evaluate its in vivo-in vitro correlation (IVIVC). METHODS:HPLC method was adopted to determine the accumulative dissolution(Q) of Cinacalcet hydrochloride tablets in 8 kinds of medium [pH 1.2 hydrochloric acid solution,pH 2.0 hydrochloric acid solution,pH 4.5 acetate buffer solution,pH 6.8 phosphate buffer solution,water,artificial gastric fluid(SGF),full belly artificial intestinal fluid(FeSSIF),fasting artificial intestinal fluid(FaSSIF)],and the dissolution curves were drawn. HPLC-MS method was used to determine the blood concentrations of Cinacalcet hydrochloride tablets. A total of 12 healthy male volunteers were selected and given single oral dose of Cinacalcet hydrochloride tablets 75 mg under the state of fasting or satiety(high-fat food). The blood concentration of cinacalcet hydrochlorid was determined before medication(0 h)and 0.5,1,2,3,4,6,8,12,24 h after medication. Average blood concentration-time curves were drawn. The in vivo accumulative absorption percentage (F) of satiety group was calculated by using DAS 3.0 software. Linear regression of F with in vitro Q was carried out to analyze its IVIVC. RESULTS:There was great difference among dissolution curves of Cinacalcet hydrochloride tablets in 8 kinds of dissolution mediums. There were differences of AUC0→t,AUC0→∞ and cmax between fasting group and satiety group,with statistical significance(P＜0.05),showing high-fat food had significant effect on in vivo pharmacokinetics. Correlation coefficient of in vivo F in satiety group with in vitro Q of the tablets in FeSSIF was highest (0.977 9),manifesting good IVIVC (class A). CONCLUSIONS:The in vitro dissolution behavior of Cinacalcet hydrochloride tablets in FeSSIF(paddle method,50 r/min)is well associated with its in vivo pharmacokinetics,which can be used for predicting in vivo dissolution and absorption of the tablets.

Objective To explore the curative effects of pulmonary surfactant (PS) injected via venous indwelling needle instead of the endotracheal tube combined with continuous positive airway pressure(CPAP) in the treatment of premature infants with neonatal respiratory distress syndrome (NRDS).Methods 28 premature infants with NRDS were selected,12 cases with gestational age of 28-31 weeks,16 cases with gestational age of 32-34 weeks,and all the cases were treated with PS injected via venous indwelling needle combined with CPAP.The changes in clinical symptoms,blood gas analysis,oxygen saturation,and the parameters of CPAP after treatment were observed.The tracheal intubation in 72h,the second use of PS,respiratory support duration,hospital duration,and the complications between the MIST treatment group and INSURE treatment group were compared.Results There were significant differences in changes of clinical symptoms,percutaneous oxygen saturation,pH,partial pressure of oxyge,partial pressure of carbon dioxide,fraction of inspiration O2 and (positive end expiratory pressure) PEEP after treatment(all P ＜ 0.05).There were statistically significant differences in tracheal intubation in 72h,the second use of PS,complications and respiratory support duration between the MIST group and INSURE group (all P ＜ 0.05).There were no statistically significant differences in bronchopulmonary dysplasia,ROP,PDA,intracranial hemorrhage,and hospital duration (all P ＞ 0.05).Conclusion The therapy of PS injected via venous indwelling needle combined with CPAP in the treatment of premature infants is effective.The method MIST is simple and convenient,has less injury to premature infants,and can reduce frequency and dosage of the PS and respiratory support time.

Objective:To analyze one case of unreasonable drug use to promote reasonable drug use in clinics. Methods: The treatment regimen with irrational drug use for one case of type 2 diabetes with complicated urinary tract infection were analyzed, and the reasons for the irrationality were summarized and some suggestions for avoiding unreasonable drug use were put forward. Results:The choice of moxifloxacin in the initial treatment was irrational, and no combination indications were shown. Clinical pharmacists partici-pated in the ward rounds and timely communicated with the clinicians to correct the drug use. Conclusion:Due to the drug resistance, pharmacokinetic characteristics and adverse reactions, moxifloxacin is unsuitable for the anti-infection treatment of complicated urinary tract infection. Clinical pharmacists should provide individualized treatment for patients to improve the effectiveness of drug therapy.

Objective:To analyze one case of unreasonable drug use to promote reasonable drug use in clinics. Methods: The treatment regimen with irrational drug use for one case of type 2 diabetes with complicated urinary tract infection were analyzed, and the reasons for the irrationality were summarized and some suggestions for avoiding unreasonable drug use were put forward. Results:The choice of moxifloxacin in the initial treatment was irrational, and no combination indications were shown. Clinical pharmacists partici-pated in the ward rounds and timely communicated with the clinicians to correct the drug use. Conclusion:Due to the drug resistance, pharmacokinetic characteristics and adverse reactions, moxifloxacin is unsuitable for the anti-infection treatment of complicated urinary tract infection. Clinical pharmacists should provide individualized treatment for patients to improve the effectiveness of drug therapy.

Objective To investigate the clinical features and drug resistance of neonatal purulent meningitis caused by Escherichia coli. Methods The clinical data of 46 neonates diagnosed with purulent meningitis caused by Escherichia coli were retrospectively analyzed from June 2004 to June 2014. The neonates were divided into community acquired infection group and nosocomial infection group, or early group (from June 2004 to May 2009) and late group (from 2009 June to June 2014). Result Fever, hypothermia, lethargy, poor feeding, tachypnea, and tachycardia were common clinical manifestations in all neonates. The detection rate of ESBLs was signiifcantly higher in nosocomial infection group than that in community acquired infection group (P?