Investigation and Analysis of the Scientific Research Status Quo of Hospital Pharmacists in China / 中国药房

OBJECTIVE：To provide evidence for promoting the scientific resea rch ability and talent team construction of hospital pharmacists. METHODS ：From Dec. 2019 to Apr. 2020，“Survey Form for Scientific Research Ability of Hospital Pharmacists”were issued to pharmacists in 62 medical institutions from 20 provinces across the country. The questionnaire was mainly based on five aspects ，i.e. general information of surveyed pharmacists ，the number of internal/external funds and patents approved in recent five years （2015-2019），the number of papers published in domestic/abroad/SCI journals ，the familiarity with scientific research projects ，the difficulties in carrying out scientific research. The collected data were summarized and analyzed with R 4.0.3 software. RESULTS ：A total of 300 questionnaires were sent out ，and 288 valid questionnaires were collected with effective recovery rate of 96％. Among surveyed pharmacists ，94 were male and 194 were female. The majority of them were 31-39 years old （52.78％）；56.25％，28.12％ and 15.63％ of them had bachelor ’s degree ，master’s degree and doctor ’s degree respectively，and 156（54.17％）had intermediate title. Totally 74.66％ of hospital pharmacists thought it was very necessary or necessary to carry out research projects （involving all doctors ，26 masters and 4 bachelors）. There were significant differences among pharmacists with different educational background in respects of the number of applications for internal and external funds and patents ，as well as the number of papers published in domestic/foreign/SCI journals ，and most of them were doctors （P＜ 0.05）. In recent five years ，most of hospital pharmacists had published 1-3 papers in domestic journals ，accounting for 44.80％， while 27.08％ had published papers in SCI journals. Totally 51.39％ of hospital pharmacists were not familiar or not very familiar with scientific research projects funding （most of them had bachelor ’s degree ）；52.43％ expressed that experimental conditions were the biggest difficulty in conducting scientific research. CONCLUSIONS：This survey shows that hospital pharmacists have a relatively positive attitude towards scientific researchprojects. Most of papers are published in domestic journals. 8804919。E-mail：songjc1234@126.com However， there are still many shortcomings in scientific research status. Scientific research capabilities need to be improved. Experimental conditions also limit the scientific research projects to a certain extent. Hospitals need to strengthen funding for pharmacist research projects ，strengthen academic exchanges ， so that pharmacists can understand scientific research projects more comprehensively and systematically.

Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)

The sigma-1 receptor (R) is a unique intracellular protein. R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, PET/CT imaging of novel R C-labeled radioligands based on 6-hydroxypyridazinone, [C]HCC0923 and [C]HCC0929. Two radioligands have high affinities to R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds and (self-blocking). Of the two, [C]HCC0929 was further investigated in positive ligands blocking studies, using classic R agonist SA 4503 and R antagonist PD 144418. Both R ligands could extensively decreased the uptake of [C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined . These studies demonstrated that two radioligands, especially [C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of R in brain.

Review on Pharmacoeconomics Evaluations of Gastroesophageal Reflux Disease / 中国药师

Gastroesophageal reflux disease is a common disease of digestive system. With the increase of domestic morbidity, the burden on the medical and health care system is correspondingly increased. The treatments of gastroesophageal reflux disease are mainly drug therapy and surgical treatment. With the increase in the number of selectable drugs and the emergence of new surgical techniques, it is particularly necessary to consider pharmacoeconomics of the plan while ensuring safety and effectiveness, especially in the context of the lack of overall medical and health resources in the country. The study of pharmacoeconomics considers different prevention, diag-nosis and treatment strategies from the perspective of economics, and provides reference for clinical treatment decision. The article re-viewed recent advances in pharmacoeconomics evaluations of gastroesophageal reflux disease.

Research Progress in N-Acetylcysteine Used in the Therapy for Autism and Obsessive-compulsive Related Disorders / 中国药师

In recent years, a considerable number of studies have shown that N-acetylcysteine( NAC) is a promising agent in the treatment of a variety of neuropsychiatric disorders. The present article briefly outlined its role in the regulation of these disorders and reviewed the current literatures on the use of NAC in autism and obsessive-compulsive related disorders(OCRD)in order to provide ba-sis for the clinical application of NAC in neuropsychiatric field.

Inhibitory Effect of Total Alkaloids from Lotus Seed on Human Hepatoma Cells / 中国药师

Objective: To study the inhibitory effect of total alkaloids from lotus seed on human hepatoma HepG2 cells.Methods: The effect of total alkaloids from lotus seed on the growth of HepG2 cells was studied by CCK-8 kit.The apoptosis rate of HepG2 cells was detected by flow cytometry.Results: When the action time was the same, with the increase of drug concentration, the inhibitory rate of total alkaloids from lotus seed on HepG2 cells increased, in a dose-dependent manner.At 72 h, the half inhibitory concentration (IC50) of total alkaloids from lotus seed on HepG2 cells was 1.501 μg·ml-1.At the same concentration, the inhibitory rate of the total alkaloids from lotus seed on HepG2 cells increased with the extension of the action time.At 72 h, the inhibition rate of 10 μg·ml-1 total alkaloids from lotus seed reached 72%.After treated with the total alkaloids from lotus seed at different concentrations, the apoptosis rate of HepG2 cells significantly increased in a dose-dependent manner.Compared with the blank control group, the difference was statistically significant (P <0.05), and the apoptosis rate of HepG2 cells was 85.6% treated with 20 μg·ml-1 total alkaloids from lotus seed.Conclusion: The total alkaloids from lotus seed can induce cell apoptosis and inhibit the proliferation of human hepatoma HepG2 cells.

Research Progress in the Drugs for Drug-resistant Herpesviruses / 中国药师

Herpesviruses is one of the most common human infectious diseases, which can be divided into different types based on clinical infection degree.Herpes simplex virus usually results in buccal and genital mucocutaneous infections, while cytomegalovirus is the most common opportunistic pathogen associated with significant morbidity and mortality in immunocompromised hosts, especially in transplant and cancer patients.Although nucleoside analogues are effective antiviral drugs, the emergence of drug-resistant viruses has created a barrier for the treatment of herpesviruses infections, especially in immunocompromised patients.Therefore, novel therapeutic agents are needed to avoid the limitations of drug resistance.In this article, research progress in the therapeutic agents for drug-resistant herpesviruses was reviewed from the aspects of non-nucleoside analogues, novel antiviral targets and newly antiviral mechanisms.

CCL2 induces epithelial-mesenchyme transition in breast cancer MCF-7 cells / 中国医师杂志

Objective To explore the effect and molecular mechanism of CC chemokine ligand 2 (CCL2) on epithelial-mesenchymal transition in human breast cancer cells.Methods Breast cancer Michigan cancer foundation-7 (MCF-7) cells were treated with 50 ng/ml CCL2.The abilities of invasion were detected by Transwell assay.The expression of epithelial-mesenchymal transition (EMT)-associated markers,E-cadherin and vimentin were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).The expressions of Snail,protein kinase B (AKT),phosphorylated protein kinase B (p-AKT),phosphorylated glycogen synthase kinase 3β (p-GSK3β3) and GSK3β were detected by Western blot.Snail nuclear localization was detected by immunoflurescence staining.Results We found that CCL2 treatment could induce morphological alteration of MCF-7 cells from epithelial morphology to mesenchymal morphology.CCL2 significantly increased the migration of MCF-7 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More important,treatment of CCL2 significantly increased the expression of Snail,and promoted the nuclear localization of Snail.Knockdown of Snail significantly reverse the effects of CCL2 on the EMT in MCF-7 cells.Moreover,treatment of CCL2 significantly increased the phosphorylation levels of p-AKT and p-GSK3β,and AKT inhibitor LY294002 significantly inhibited CCL2-induced Snail and p-GSK3β expression.Conclusion CCL2 might induce EMT in MCF-7 cells,by which mechanism is related to activate AKT/GSK3β Snail pathway.

Application Investigation and Analysis of Fibrinogen in Our Hospital / 中国药师

Objective:To investigate the clinical application of fibrinogen (FIB) in a certain hospital to enhance the rational use in clinics.Methods:A retrospective investigation was adopted to analyze the clinical application of FIB in a certain hospital in 2016. Results:Totally 489 inpatients were treated with FIB in 2016,and among them,243 cases were surgery patients and another 246 ones were non-surgery patients. The main involved departments were cardiovascular surgery,cardiovascular medicine,emergency,intensive medicine,gynaecology and obstetrics, gastroenterology and neurosurgery. The rationality of indication was 80.0% (391/489), and the non-indication use mainly existed in cardiovascular surgery and cardiovascular medicine departments. Among the 391 cases with in-dication,3 cases were with improper compatibility,17 cases with low dosage, and the irrationality of usage and dosage was 17.9% (20/391). Conclusion:The clinical application of FIB is basically rational in the hospital,while non-indication use still exists during the perioperative period in cardiovascular and cerebrovascular surgery,and nonstandard usage and dosage appear in clinics from time to time. The prescription comment on blood products such as FIB should be enhanced in order to improve the rational use in clinics.

Effects of Neferine on Proliferation and Apoptosis of HepG2 Cells / 中国药师

Objective:To investigate the effects of neferine on the proliferation and apoptosis of HepG2 cells. Methods: The effect of neferine on the proliferation of HepG2 cells was determined by cell counting kit-8 (CCK-8), the morphology of HepG2 cells with Hoechst33258 staining was observed under a fluorescent microscope,the degree of damage to HepG2 cells was observed by lactate dehydrogenase (LDH) kit,Annexin V /propidium iodide (PI) and PI/Rnase were used to analyze the apoptosis and the cell cycle. Results:Neferine could inhibit the proliferation of HepG2 cells in a dose and time-dependent manner,and the degree of damage to the cell membrane increased with the dose of the drug. The results of Hoechst33258 staining and flow cytometry (FCM) indicated that HepG2 cells were arrested in G0/G1phase and the apoptotic rate increased with the concentration increase of neferine.Conclusion:Neferine can inhibit the growth and proliferation of HepG2 cells in a dose and time-dependent manner, induce it arrested in G0/G1 phase and induce the late apoptosis of HepG2 cells.

Optimization of Formula and Preparation Process and Content Determination of Sorafenib Dry Suspension / 中国药师

Objective:To optimize the formula and preparation process of prepare sorafenib dry suspension and detect the content by HPLC. Methods:The influence of single factor including different fillers, suspending agents, adhesives and disintegrants on the sedimentation rate, redispersibility and drying shrinkage of sorafenib dry suspension was observed. Orthogonal design was used to opti-mize the formula and preparation process of the suspension, and HPLC was used to determine the content of sorafenib. The chromato-graphic column was Inertsil ODS-3 (250 mm × 4. 6 mm, 5μm), the mobile phase was 20 mmol·L-1 ammonium acetate buffer-aceto-nitrile(28 ∶72), the detection wavelength was 266 nm, the flow rate was 1. 0 ml·min-1, the column temperature was 40℃, and the sample size was 20 μl. Results:The optimal formula and preparation process were as follows:sucrose (48%) was used as the filler, xanthan gum (28%) and CMC-Na (12%) were the suspending agents, MCC (10%) was used as the disintegrant, and 6% PVP (in 50% ethanol) was the adhesive. The linear range of sorafenib was 1-100 μg·ml-1(r=0.999 8), and the recovery was 98.96%(RSD=0. 75%, n=9). Conclusion:The optimal formula and preparation process are repeatable. The HPLC method is simple and specific, which can be used to determine sorafenib.

Determination of Entrapment Efficiency of Buthionine Sulfoximine Nanoparticles in Different Entrapping Systems by HPLC / 中国药师

Objective:To establish an HPLC method to determine the entrapment efficiency of buthionine sulfoximine (BSO) nan-oparticles in different entrapping systems .Methods:Free BSO was separated from the loaded nanoparticles by high speed centrifugation in two entrapping systems and the entrapment efficiency of buthionine sulfoximine nanoparticles was determined by HPLC .A WondaSil C18 column (250 mm ×4.6 mm, 5 μm) was used and the mobile phase was methanol-water (20 ∶80).The flow rate was 0.4 ml· min-1 and the column temperature was 30℃.The detection wavelength was set at 210 nm and the volume of injection was 20 μl.Re-sults:BSO had a good linear relationship within the range of 2.0-320.0μg· ml-1(r=0.999 7).The average recovery was 101.05%and RSD was 0.74%(n=9).The average entrapment efficiency of HP/CaCO3/CaHPO4/BSO nanoparticles and HP/PS/CaCO3/BSO hydrid nanovesicles was 25.63% and 58.62%, respectively.Conclusion:The method has good repeatability and high accuracy and sensitivity, which is applicable to determine the entrapment efficiency of BSO nanoparticles .HP/PS/CaCO3/BSO hydrid nanovesicles entrapped system is superior to HP/CaCO3/CaHPO4/BSO nanoparticles entrapped system .

Rationality Evaluation of Drug Use in Children with Rotavirus Enteritis by Children Drug Utilization Index / 中国药师

Objective:To evaluate the rationality of drug use in the children with rotavirus enteritis by the children drug utilization index ( cDUI) . Methods:A retrospective analysis was used to investigate the cDUI, DDDs and rationality of cimetidine, saccharomy-ces boulardiiand and ganciclovir used in 78 children with rotavirus enteritis. Results and Conclusion: The value order of DDDs was saccharomyces boulardii>cimetidine >ganciclovir. Moreover, the dosage of cimetidine and saccharomyces boulardii was relatively high, while that of ganciclovir was basically rational.

Research Advances in Pharmacological Effects of Nuciferine / 中国药师

Nuciferine is a major aporphine alkaloid in the leaves of Nelumbo nueifera. It has great effects such as lipid-lowering,anti-oxidation,antimicrobial activitity and anti-cancer. The review focused on its pharmacological effects and pharmacokinetic characters reported in recent years,which can be helpful to the further researches on nuciferine.

Inhibitory Effect of Neferine and Isoliensinine on 5α-Reductase / 中国药师

Objective:To compare the inhibitory effect of neferine and isoliensinine on 5α-reductase to provide reference for the development of 5α-reductase inhibitors. Methods: Different reaction tubes and control tubes were prepared, liver was homogenated, and reducing coenzyme II ( NADPH) , testosterone, pending test sample, the positive drug and buffer was respectively added into 96-well plates. The change in the absorbance of NADPH at 340nm in 1h was determined by a microplate reader. Compared the experimen-tal group with the blank control group, the inhibition rate ( I%) of the test drugs against 5α-reductase was calculated. Results:As for the six concentration gradients (2-40 mg·ml-1 ) in the experiments, the best inhibitory concentration of neferine and isoliensinine was 10 mg·ml-1(I% =25.00 ±1.030% and 29.90 ±2.410%, respectively). Compared with the control group, neferine and isoliensi-nine showed significant inhibition against 5α-reductase (P<0. 05). Compared with the positive group at the same concentration (10 mg ·ml-1), the inhibition of neferine and isoliensinine was significantly lower (P<0. 05). The inhibition effect of isoliensinine was rel-atively better than that of neferine (P<0. 05). Conclusion:Neferine and isoliensininein have notable inhibitory effect on 5α-reduc-tase, which show certain application prospect in the treatment of prostatic hyperplasia in clinics.

Pharmaceutical care for advanced small cell lung cancer patient associated with renal insufficiency / 药学实践杂志

Objective To monitor the medication process of advanced lung cancer patients with renal insufficiency .Meth‐ods Pharmaceutical care ,pharmaceutical intervention and medication were offered according to the individual condition of pa‐tient with renal function based on pharmaceutical experience and related literature .Results The patient finished chemotherapy successfully without adverse reaction .Conclusion Clinical pharmacists should keep improving their knowledge and participat‐ing in first‐line clinical treatment activities;the patient‐centered hospital pharmacy service will be founded and the level of ra‐tional medication will be improved when doctors ,pharmacists and nurses could cooperate sincerely .

Investigation of Xingnaojing Injection Applied in the Patients of Neurosurgery Department in a Certain Hospital / 中国药师

Objective:To investigate the application of Xingnaojing injection ( XNJI) in the patients of neurosurgery department to provide reference for the rational drug use. Methods:The retrospective investigation was applied to survey 200 hospitalization records with XNJI from a certain hospital between January 2014 and June 2015. The usage, dosage, medication purpose, course of treatment, compatibility and adverse effects of XNJI were analyzed. Results:The unlabeled use of XNJI was found in neurosurgery department, and 34. 50% of the surveyed patients were found that their diagnoses didn’t conform to the indications in the medicine specification of XNJI. Moreover, 92. 50% of the inpatients were treated with overdose and almost 90. 00% were treated with single drug dose of 40 ml. It was also found that XNJI was often combined with potassium chloride or with potassium chloride plus insulin in clinical use. Conclu-sion:There is some irrational use of XNJI in clinics, thus the use and management of traditional Chinese medicine injections should be strengthened and regulated.

Protective Effects of Neferine on Lipopolysaccharide-induced Human Umbilical Vein Endothelial Injury / 中国药师

Objective:To investigate the protective effects of neferine on lipopolysaccharide ( LPS)-induced human umbilical vein endothelial cells ( HUVECs) injury. Methods:The optimum inducing concentration of LPS was screened out through pretests and used for the model establishment of HUVECs damage. CCK8 was used to detect the influence of neferine at different concentrations on LPS-induced human umbilical vein endothelial cells ( HUVECs) injury. Nitric oxide ( NO) content was measured by the Griess Reagent method. The nitric-oxide synthase (NOS) activity was assessed by the commercially available kits. Results:The inhibitory rate of HU-VECs was 54. 50% detected by CCK8, which induced by LPS at the concentration of 100 μg·ml-1(P<0. 01). Neferine at the con-centrations of 0. 3-5. 0μmol·L-1 could increase the cell viability in a concentration-dependent manner, while it inhibited the cell pro-liferation at the concentration of 10 μmol·L-1(P<0.05). Neferine could reverse the situation, and the NO release was increased and the tNOS/iNOS activity was increased induced by LPS (P<0. 05). The results shown by the inverted microscope suggested that the floating dead cells were decreased, the cell shape was basically sound and tightly packed with the concentration increase of neferine (0. 3-5. 0μmol·L-1) in a concentration-dependent manner. Conclusion:The results show that neferine has protective effects on HU-VECs injury induced by LPS, and the mechanism may be related with the decrease of intracellular levels of NO and NOS activity.

Study on Anti-RSV Activity of Natural Curcuminoids / 中国药师

Objective:To study the anti-human respiratory syncytial virus ( RSV) activity of natural curcuminoids in Curcuma lon-ga in vitro. Methods:The anti-RSV activity of ethyl acetate part of 95% ethanol extracts of Curcuma longa and natural curcuminoids in Curcuma longa in vitro were detected by cytopathic inhibition method. Results:Bisdemethoxycurcumin exhibited anti-RSV activity with IC50 of 12. 5 μg·ml-1 and SI of 1. Conclusion:Natural curcuminoids in Curcuma longa exhibit anti-RSV activity.

Analysis and Pharmaceutical Care Performed by Clinical Pharmacist for 2 Cases of Drug-induced Acute Kidney Injury / 中国药师

Objective: To provide some experience and help for the pharmaceutical care for drug-induced acute kidney injury through analysis and pharmaceutical care performed by clinical pharmacist for two cases of drug-induced acute kidney injury. Meth-ods:Clinical pharmacist analyzed the mechanism of drug-induced acute kidney injury, provided some suggestions for the medication, helped doctors select hormone drugs reasonably and performed medical education in the patients. Results:The kidney function of the two patients was recovered during the hospitalization after the reasonable treatment and care by doctors and pharmacists. Conclusion:The drug-induced acute kidney injury should be paid high attention, and the medical education should be strengthened in the patients.

Anti-inflammatory, Analgesia and Antipyretic Effects of Chaige Qingre Granules / 中国药师

To investigate the anti-inflammatory, analgesia and antipyretic effects of Chaige Qingre granules. Meth-ods:Kunming mice were used to make auricle swelling model by dimthylphenanthrene, and the auricle swelling degree was measured to test the anti-inflammatory effect of Chaige Qingre granules. Mice were used to make pain models by acetic acid, and the body twis-ting of the mice was counted to observe the analgesia effect of the granules. The fever model in rats was induced by yeast, and the body temperature of the rats was measured to investigate the antipyretic effects of the granules. Results:Chaige Qingre granules could relieve the auricle swelling degree significantly, and the inhibition rate was 46. 3% in the high dose group. High and middle dose groups could reduce the body twisting frequency with the inhibition rate of 51. 1% and 61. 8%, respectively. Every Chaige Qingre granules group could lower the body temperature after one hour of the administration, and the temperature could be reduced 0. 56 degrees Celsius in the high dose group. Conclusion:Chaige Qingre granules can effectively inhibit auricle swelling degree, relieve pain and reduce heat.