Objective To investigate the impacts of neferine on cellular autophagy and apoptosis,and the silent mating type information regulation 2 homolog-1/5'-AMP activated protein kinase activated protein kinase/mammalian target of rapamycin(SIRT1/AMPK/mTOR)signaling path-way in acute myocardial infarction(AMI)rats.Methods A rat model of AMI was constructed on male SD rats,and then 72 successfully modeled rats were randomly divided into model group,low-and high-dose neferine groups,and high-dose neferine+SIRT1 inhibitor(EX-527)group,with 18 rats in each group.Another 18 normal rats served as the Control group.The area of myocardial infarction,expression of myocardocyte autophagy related proteins,myocardocyte apoptosis,and expression of SIRT1/AMPK/mTOR signaling pathway-related proteins were observed and detec-ted in above groups of rats.Results When compared with the model group,the low-and high-dose neferine groups exhibited milder pathological injuries,higher left ventricular ejection frac-tion,enhanced left ventricular fractional shortening,increased optical densities of microtubule associated protein 1 light chain 3(LC3)Ⅱ and Beclin-1,and elevated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),and shorten left ventricular end-systolic diameter,lessened area of myocardial infarction,lower apoptotic rate,and reduced expres-sion of Bax and p-mTOR/mTOR(P＜0.05).While,in comparison to high-dose neferine treat-ment,addition of SIRT1 inhibitor,EX-527 resulted in more severe myocardial injuries,decreased left ventricular ejection fraction and left ventricular fractional shortening values,reduced optical densities of LC3 Ⅱ and Beclin-1,and down-regulated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),but increased left ventricular end-systolic diame-ter,larger myocardial infarction area,increased apoptotic rate,and increased expression levels of Bax and p-mTOR/mTOR(P＜0.05).Conclusion Neferine can inhibit apoptosis and promote autophagy in AMI rats and exert myocardial protective effects,which may be related to the activa-tion of the SIRT1/AMPK/mTOR signaling pathway.

Objective To investigate the impacts of neferine on cellular autophagy and apoptosis,and the silent mating type information regulation 2 homolog-1/5'-AMP activated protein kinase activated protein kinase/mammalian target of rapamycin(SIRT1/AMPK/mTOR)signaling path-way in acute myocardial infarction(AMI)rats.Methods A rat model of AMI was constructed on male SD rats,and then 72 successfully modeled rats were randomly divided into model group,low-and high-dose neferine groups,and high-dose neferine+SIRT1 inhibitor(EX-527)group,with 18 rats in each group.Another 18 normal rats served as the Control group.The area of myocardial infarction,expression of myocardocyte autophagy related proteins,myocardocyte apoptosis,and expression of SIRT1/AMPK/mTOR signaling pathway-related proteins were observed and detec-ted in above groups of rats.Results When compared with the model group,the low-and high-dose neferine groups exhibited milder pathological injuries,higher left ventricular ejection frac-tion,enhanced left ventricular fractional shortening,increased optical densities of microtubule associated protein 1 light chain 3(LC3)Ⅱ and Beclin-1,and elevated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),and shorten left ventricular end-systolic diameter,lessened area of myocardial infarction,lower apoptotic rate,and reduced expres-sion of Bax and p-mTOR/mTOR(P＜0.05).While,in comparison to high-dose neferine treat-ment,addition of SIRT1 inhibitor,EX-527 resulted in more severe myocardial injuries,decreased left ventricular ejection fraction and left ventricular fractional shortening values,reduced optical densities of LC3 Ⅱ and Beclin-1,and down-regulated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),but increased left ventricular end-systolic diame-ter,larger myocardial infarction area,increased apoptotic rate,and increased expression levels of Bax and p-mTOR/mTOR(P＜0.05).Conclusion Neferine can inhibit apoptosis and promote autophagy in AMI rats and exert myocardial protective effects,which may be related to the activa-tion of the SIRT1/AMPK/mTOR signaling pathway.

Objective:To investigate the impact of neferine(NEF)on the blood-brain barrier in ischemic stroke(IS)rats by regulating the CC chemokine ligand 2(CCL2)-CC chemokine receptor 2(CCR2)signal pathway.Methods:SD rats were randomly divided into model group,low-dose NEF group(NEF-L group,25 mg/kg NEF),high-dose NEF group(NEF-H group,50 mg/kg NEF),and high-dose NEF+CCR2 antagonist group(NEF-H+RS102895 group,50 mg/kg NEF+10 mg/kg RS102895),sham opera-tion group(Sham group),with 15 rats in each group.The neurological function scores of rats in each group were compared.The perme-ability of blood-brain barrier of rats in each group was evaluated by Evans blue(EB)permeation method.The water content of brain tis-sue of rats in each group was determined by dry and wet weight method.The expression levels of CCL2 and CCR2 mRNA in rat brain tissue were measured by real-time fluorescence quantitative PCR(RT-qPCR).The expression levels of CCL2,CCR2,ZO-1 and Clau-din-5 proteins in rat brain tissue were detected by Western blot.Results:Compared with Sham group,the neural function score,EB content,water content,the expression levels of CCL2,CCR2 mRNA and protein in the right brain tissue of the model group were obvi-ously higher(P<0.05),the expression levels of ZO-1 and Claudin-5 were lower(P<0.05).Compared with the model group,the neuro-logical function score,water content,EB content,the expression levels of CCL2,CCR2 mRNA and protein in the right brain tissue of rats in the NEF-H group were obviously lower(P<0.05),the expression levels of ZO-1 and Claudin-5 were obviously higher(P<0.05).RS102895 enhanced the protective effect of NEF on the blood-brain barrier in IS rats.Conclusion:NEF may protect the blood-brain barrier of IS rats by inhibiting CCL2-CCR2 signal pathway.

We provided pharmaceutical care for a cryptococcal meningitis case to study the role that clinical pharmacists played in clinical pharmacotherapy.In this case,clinical pharmacists gave advice on drug therapy strategy which was mostly accepted by physicians.During the whole course of drug treatment,focused on monitoring,prevention,and treatment of adverse reactions,clinical pharmacists carried out pharmaceutical care on efficacy,safety,economics and compliance of drug therapy.After 73 days' treatment,with CSF cryptococcal count negative twice and physical condition improved,the patient was discharged.No serious adverse reaction was observed in the period of treatment.The total pharmaceutical care was completed as planned.Through participating in the formulation of treatment strategy and carrying out pharmaceutical care,clinical pharmacists can play a role in improving the efficacy and safety of drug therapy in cryptococcal meningitis.Abstract:SUMM ARY W e provided pharmaceutical care for a cryptococcal meningitis case to study the role that clinical pharmacists played in clinical pharmacotherapy.In this case,clinical pharmacists gave advice on drug therapy strategy which was mostly accepted by physicians.During the whole course of drug treat-ment,focused on monitoring,prevention,and treatment of adverse reactions,clinical pharmacists carried out pharmaceutical care on efficacy,safety,econom ics and compliance of drug therapy.After 73 days’ treatment,with CSF cryptococcal count negative twice and physical cond ition improved,the patientwas d ischarged.No serious adverse reaction was observed in the period of treatment.The total pharmaceutical care was completed as planned.Through participating in the formulation of treatment strategy and carrying out pharmaceutical care,clinical pharmacists can play a role in improving the efficacy and safety of drug therapy in cryptococcalmeningitis.