Research progress and clinical application of liposomal drug delivery system / 中国药房

With the advantage of high efficiency， low toxicity and targeting， liposomes have become the research hotspot of new drug preparations at home and abroad. In this paper， the research progress in recent years is reviewed from the aspects of preparation methods， classification and clinical application of liposomes. The results showed that in order to obtain more stable and controllable liposomes， scholars improved and optimized the traditional preparation methods and established novel preparation methods such as supercritical fluid methods， freeze-drying method and double-asymmetric centrifugation method. In order to enhance the efficacy and reduce toxicity， the conventional liposomes were optimized to get novel ones such as environmentally sensitive liposomes， long-circulating liposomes and multifunctional liposomes， which had greatly promoted the clinical application of liposomes. For now， liposomes have been used in many fields， such as anti-cancer agents， antimicrobial and vaccines， but most of the new liposomes are still in the early stage of development.

Clinical Characteristics of Voriconazole-induced Neurological ADR and the Occurrence of Hypokalemia and Hyponatremia / 中国药房

OBJECTIVE：To explo re the clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia before ADR. METHODS ：The medical records of 411 patients receiving voriconazole therapy ， who admitted to our hospital from January 2018 to November 2020，were retrospectively analyzed. The general information of all patients，including sex ，age，body weight ，type of infection ，underlying disease ，type of pathogenic fungal infection and administration route of voriconazole ，maintenance dose ，blood drug concentration ，were collected. The basic information of patients with neurological ADR ，including sex ，age，types of infection ，underlying disease ，drug combination ，occurrence time and clinical manifestations ，were collected . The levels of blood potassium ，blood sodium and liver function indexes （ALT，AST， γ-GT，ALP，total bilirubin ，direct bilirubin ）within 3 days before the neurological ADR were also collected. The relationship of neurological ADR with voriconazole trough concentration ，blood potassium and blood sodium levels was analyzed. RESULTS ： Among 411 patients，31（7.54％）patients suffered from neurological ADR ，which were higher in male （64.52％）than in female （35.48％），mainly in patients aged 50 and over （74.20％）. The major infection type was lung infection （96.77％）. Among 31 patients with neurological ADR ，26 patients suffered from neurological ADR after 1-7 days after voriconazole administration ， accounting for 83.87％. Thirty patients received intravenous drip ，accounting for 96.77％. The incidence of neurological ADR in patients with voriconazole trough concentration ＞5.0 μ g/mL （8.99％）was significantly higher than that in patients with trough concentration ≤5.0 μg/mL（3.42％，χ2＝4.91，P＝0.027）. The clinical manifestations of the patients were mainly 023-68766797。E-mail：cheng7zhu@163.com hallucinations（32.35％），irritability（32.35％）and poor sleep （17.65％），etc. Within 3 days before 30 patients，receiving related indexes test ，suffered from neurological ADR ，16 patients（53.33％）had hypokalemia and 12 patients（40.00％） had hyponatremia ，which w ere significantly higher than the incidence of hypokalemia （24.74％，P＝0.001）and hyponatremia （12.89％，P＜0.001）in those without neurological ADR . There were 8，10，7，13，7 and 10 patients with ALT ，AST，ALP， γ-GT，total bilirubin and direct bilirubin increased. In 31 patients with neurological ADR ，the neurological ADR were relieved or disappeared after reducing the dosage or discontinuing voriconazole. CONCLUSIONS ：The neurological ADR of voriconazole mostly occurs 1-7 days after voriconazole administration ，mainly by intravenous drip ，mostly in male and people aged 50 and over. The occurrence of neurological ADR may be related to trough concentration of voriconazole ，and most patients suffer from hypokalemia or hyponatremia before the occurrence of ADR .

Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes Mellitus ：A Systematic Review / 中国药房

OBJECTIVE：To systematically evaluate th e efficacy and safety of glucagon-like peptide 1 receptor agonists semaglutide in the treatment of type 2 diabetes mellitus （T2DM），and to provide evidence-based reference for clinical treatment of T2DM. METHODS ：Retrieved from PubMed ，Embase，the Cochrane library ，ClinicalTrials.gov，CBM，CNKI and VIP ， randomized controlled trials （RCT） about oral semaglutide 3 mg，7 mg and 14 mg （trial group ） versus placebo or other glucose-lowering drugs （control group ）in the treatment of T 2DM were selected during the inception to May 2020. After extracting data from clinical studies that met the inclusion criteria ，quality evaluation was carried out with Cochrane systematic evaluation manual 5.1.0，Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS ：A total of 6 RCTs involving 5 334 patients were included. Results of Meta-analysis showed that compared with control group ，trial group could significantly decreased HbA 1c level { 26 weeks [MD＝－0.62，95％CI（－0.88，－0.36），P＜0.001]，52 weeks [MD＝－0.51，95％CI（－0.72， －0.29），P＜0.001]}，FPG level { 26 weeks [MD＝－0.89，95％ CI（－1.31，－0.48），P＜0.001]，52 weeks [MD＝－0.68，95％CI （－1.05，－0.31），P＜0.001]}；significantly increased the compliance rate of HbA 1c＜7％ {26 weeks [RR＝2.22，95％CI（1.68， 2.93），P＜0.001]，52 weeks [RR＝2.02，95％CI（1.51，2.70），P＜0.001]}；significantly decreased the self-measured plasma glucose ， body weight and diastolic blood pressure （DBP）after 26 and 52 weeks of treatment，self-measured postprandial glucose cstc2015zdcy-ztzx120005） after 26 weeks of treatment and systolic blood pressure （SBP） E-mail： after 52 weeks of treatment（P＜0.05）. Subgroup analysis of different doses showed that compared with control group ，3 mg subgroup could significantly decreased the body weight after 26 and 52 weeks of treatment and DBP a fter 52 weeks of treatment ；7 mg subgroup could significantly decreased the HbA 1c levels and body weight after 26 and 52 weeks of treatment ，the FPG levels and the self-measured plasma glucose after 26 weeks of treatment and the SBP after 52 weeks of treatment ，increased the compliance rate of HbA 1c＜7％ after 26 weeks of treatment. The 14 mg subgroup could significantly decreased the HbA 1c levels ，the FPG levels ，the self-measured plasma glucose levels ，the body weight and the SBP after 26 and 52 weeks of treatment ，and self-measured postprandial glucose after 26 weeks of treatment ，while increased the complication rate of HbA 1c＜7％ after 26 and 52 weeks of treatment （P＜0.05）. The incidence of hypoglycemia events in trial group [RR ＝0.84，95％CI（0.72，0.97），P＝0.02] was significantly lower than control group ，but the incidence of adverse events [RR ＝1.23，95％CI（1.09，1.40），P＝0.001] and gastrointestinal reaction [RR ＝1.99，95％CI（1.55，2.57），P＜0.001] were significantly higher than control group. There was no significant difference in the incidence of serious adverse events or infection between 2 groups（P＞0.05）. CONCLUSIONS ：Oral semaglutide can effectively decrease blood glucose level ，increase the compliance rate of HbA 1c＜7.0％，reduce the body weight and blood pressure level of T 2DM patients ，and the 14 mg subgroup has the best effect. When using somaluptide ， we should pay attention to the occurrence of adverse events ， especially gastrointestinal adverse events.

Effectiveness of Prophylactic Use of Carbapenems for Severe Acute Pancreatitis ：A Meta-analysis / 中国药房

OBJECTIVE： To systematically evaluate effectiveness of prophylactic application of carbapenems for severe acute pancreatitis （SAP）， and to provide evidence-based reference in clinic. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane Library， CNKI and VIP database，randomized controlled trials （RCTs） about effectiveness of prophylactic application of carbapenems （trial group） versus placebo or non-prophylactic use of antibiotics （control group） for SAP were included， and the retrieval time was from establishment to Dec. 2018. After extracting data from clinical studies that met the inclusion criteria， methodological quality of included studies were evaluated by using Cochrane bias risk assessment tool 5.1.0 and modified Jadad scoring scale， and Meta-analysis was performed for pancreatic infection rate， extrapancreatic infection rate， surgical intervention rate and mortality rate by using Rev Man 5.3 statistical software. RESULTS： A total of 8 RCTs were included， involving 544 patients. Meta-analysis showed that there was no statistical significance in the pancreatic infection rate [RR＝0.84， 95％CI （0.58， 1.22）， P＝0.36]， extra-pancreatic infection rate [RR＝0.76， 95％CI （0.43， 1.35）， P＝0.35] and surgical intervention rate [RR＝0.93， 95％CI （0.65， 1.32）， P＝0.68] or mortality rate [RR＝0.99， 95％CI（0.59，1.65）， P＝0.97] between 2 groups. CONCLUSIONS： The prophylactic use of carbapenems can not reduce pancreatic or extra-pancreatic infection rate， surgical intervention rate and mortality rate.

Research progress of oral anticoagulants in patients with liver diseases / 中华肝脏病杂志

Patients with liver disease are at an increased risk of both embolism and bleeding. The optimal anticoagulation strategy remains unclear when associated with venous thromboembolic disease. Moreover, currently approved oral anticoagulant drugs undergo metabolism and elimination in the liver with varying degrees of hepatic dysfunction. Thus, impaired liver function may lead to increased risk of bleeding, making anticoagulant therapy more intricate. This article summarizes the risk of bleeding and thrombosis in patients with liver disease, and the clinical research progress of oral anticoagulants in patients with liver disease to facilitate evidence for choosing oral anticoagulants therapy when required.

Promotion of clinical pharmacy services and discipline construction based on the system of chief resident pharmacists / 中华医院管理杂志

By referring to the management model of chief residents, the system of chief resident pharmacists is established to promote the training of clinical pharmacists and the construction of clinical pharmacy disciplines. Professional clinical pharmacists are elected to be the chief resident pharmacists, who are designated based on qualification for application, appointment procedures, scope of responsibilities and job description. The establishment and implementation of the chief resident pharmacist system plays a positive role on the team building of high-quality clinical pharmacists, accelerating the development of clinical pharmacy disciplines. It can serve as an important measure to further strengthening the construction of clinical pharmacists system.

Measurement of effective constituents contents in rhubarb by capillary electrophoresis / 重庆医学

Objective To adopt the capillary electrophoresis(HPCE) for detecting the contents of emodin,chrysophanol and rhein in the extract of rheum officinale.Methods The detection was executed with a fused-silica capillary column(67.4 cm× 75.0 μm,effective length 51.0cm) as the separation column.The buffer solution consisted of 60 mmol/L Na2B4O7,40 mmol/L Na2CO3 and 40 mmol β-cyclodextrin(pH 8.9).The detection wavelength was 254 nm.Results RSD of precision in emodin,chrysophanol and rhein was 1.79％,4.46％ and 2.30％.respectively The linear range of 3 components was 1.1-19.0 mg/mL;the average recovery rates of emodin,chrysophanol and rhein were 100.14 ％,99.65 ％ and 98.44 ％ respectively,RSD was 2.43 ％,2.54 ％ and 2.02％ respectively(n=3).Conclusion The method can be used in the content determination of rheum officinale extract.

Research on standard management for quality and safety of outpatient prescription / 中华医院管理杂志

Medication safety is a top concern for medical institutions. Outpatient prescription standard is designed to standardize prescription, dispensing, and supervision for outpatient and emergency prescriptions at medical institutions. The standard covered prescription authorization management, prescription issuance, prescription dispensing, prescription saving and supervision. These four parts focus on risk exposure of patients′medication safety, and aim at safeguarding patient medication safety, which were formulated according to China′s laws and regulations, domestic and international industrial standards and technical specifications, as well as prescription conditions at medical institutions and experts opinions. The standard covers technical requirements and guidance, management measures and system development, serving as an important basis to guide medical institutions on standardize management of outpatient prescription and emergency prescription.

Discussion about Postgraduate Education Mode of Pharmaceutical Professional Degree / 中国药房

OBJECTIVE:To provide reference for the reform of the postgraduate training mode of pharmaceutical professional degree. METHODS:Domestic literatures about postgraduate training mode of pharmaceutical professional degree from 2010 to 2013 were searched and combined with the current education situation in China to conclude and summarize the existing problems and reform strategy. RESULTS:Postgraduate education mode of pharmaceutical professional degree in China was still in the explor-atory stage,with shortage of teachers,unreasonable courses,unsound educational structure,nonsupport of the students,imperfec-tion evaluation systems,and so on. Further promoting the reform of postgraduate education mode needs to strengthen teacher teams ’construction,implement cooperative training;improve training program and teaching courses;strengthen dissertation applica-tion-oriented and practice base construction;fully mobilize the enthusiasm and motivation of students;promote the connection of pharmaceutical professional training and vocational qualifications;and improve the quality assurance systems. CONCLUSIONS:Further implementation of postgraduate training mode of pharmaceutical professional degree and postgraduate education of pharma-ceutical professional degree can train the applied talents that meet social needs,improve employment rate of postgraduates and re-duce waste of educational resources.

Roles and functionality of clinical pharmacists in pharmacy administration / 中华医院管理杂志

This paper introduced the model of clinical pharmacists involving in pharmacy administration in Southwest Hospital.It features the following :1 .Establishment of the chief resident pharmacists mechanism , with clinical pharmacists involving in clinical drug treatment , therapy consultations and hospital‐wide consultations ;2 .Rational drug use quality control ,to supervise normative drug use of clinicians using the driver′s license management system for drug use;3 .Establishment of effective communication channels between physicians and pharmacists ,for mutual learning and supervision .Such model has helped clinical pharmacists to accumulate experiences in drug therapy ,and encouraged rational drug use .

Synergistic Effect of Fosfomycin Combined with Carbapenems against Drug-resistant Pseudomonas aerugi-nosa Isolated from Urinary Tract Infections in vitro / 中国药房

OBJECTIVE:To investigate synergistic effect of carbapenems combined with fosfomycin(FOS)on carbapenems-re-sistant Pseudomonas aeruginosa isolates from urinary tract infections in vitro. METHODS:The minimum inhibitory concentration was detected using agar double dilution method. The fractional inhibitory concentration index was determined by checkerboard meth-od. The effect of carbapenems combined with FOS on biofilm of P. aeruginosa isolates was determined using 96 crystal violet stain-ing. RESULTS:12 strains of carbapenem-resistant P. aeruginosa isolates were highly sensitive to FOS and amikacin,and were com-pletely resistant to imipenem and meropenem. The combination of imipenem with FOS could induce a synergistic effect on 4 strains (33.3%);meropenem combined with FOS could induce a synergistic effect on 5 strains(41.7%);no antagonistic effect of carbap-enems combined with FOS appeared. FOS combined with carbapenems could inhibit the biofilm of carbapenems-resistant P. aerugi-nosa(P<0.05 or P<0.01). CONCLUSIONS:The combination of carbapenems with FOS possesses in vitro synergistic antibacteri-al effect on part of carbapenems-resistant P. aeruginosa isolates,the mechanism of which may be associated with inhibiting the bio-film.

Analysis of biofilm formation ability and related genes of Staphylococcus aureus isolated from urinary tract infections / 重庆医学

Objective To study the biofilm formation ability and related gene distribution of Staphylococcus (S .) aureus iso‐lated from urinary tract infections to provide the theoretical basis for the prevention and treatment of clinical infection .Methods The minimal inhibitory concentration was detected using the agar double dilution method .The bacterial adhesion ability was deter‐mined by flat colony counting method .The biofilm formation ability was analyzed by the 96‐well crystal violet staining method .The biofilm‐associated genes were detected by PCR amplification .Results Eleven clinical strains of S .aureus were high resistant to pen‐icillin and erythromycin ,whereas were all sensitive to vancomycin and nitrofurantoin .All the isolates had a strong ability of adhe‐sion ,but the biofilm formation ability was weak .Among them ,the icaAD and icaBC genes were amplified in 10 S .aureus isolates . Conclusion The adhesion ability and biofilm formation ability of S .aureus isolated from urinary tract infections have the strain differences ,and ica is an important gene of S .aureus biofilm formation .

Quantification of neomangiferin in rat plasma by liquid chromatography-tandem mass spectrometry and its application to bioavailability study$ / 药物分析学报

Neomangiferin, a natural C-glucosyl xanthone, has recently received a great deal of attention due to its multiple biological activities. In this study, a rapid and sensitive ultra-high performance liquid chroma-tography tandem mass spectrometry (UHPLC–MS/MS) method for the quantification of neomangiferin in rat plasma was developed. Using chloramphenicol as an internal standard (IS), plasma samples were subjected to a direct protein precipitation process using methanol (containing 0.05% formic acid). Quan-tification was performed by multiple reactions monitoring (MRM) method, with the transitions of the parent ions to the product ions of m/z 583.1-330.9 for NG and m/z 321.1-151.9 for IS. The assay was shown to be linear over the range of 0.2–400 ng/mL, with a lower limit of quantification of 0.2 ng/mL. Mean recovery of neomangiferin in plasma was in the range of 97.76%–101.94%. Relative standard deviations (RSDs) of intra-day and inter-day precision were both o 10%. The accuracy of the method ranged from 94.20%to 108.72%. This method was successfully applied to pharmacokinetic study of neomangiferin after intravenous (2 mg/kg) and intragastric (10 mg/kg) administration for the first time. The oral absolute bioavailability of neomangiferin was estimated to be 0.53%7 0.08%with an elimination half-life (t1/2) value of 2.74 7 0.92 h, indicating its poor absorption and/or strong metabolism in vivo.

Study on Pharmaceutical care mode of the patients with chronic disease / 重庆医学

Objective To investigate the medical and pharmaceutical knowledge of patients with chronic diseases and analyse the influence factors of rational administration in patients ,to provid data to support the establishment of pharmaceutical service mode . Methods 386 cases of patients with chronic diseases were asked to finish the questionnaires for the medical and pharmaceutical knowledge ,and factors affecting the rational drug were analyzed by single factor and multiple factors Logistic regression analysis . Results Among the 386 patients ,cardiovascular and celebralvascular disease ratio was the highest(53 .3% ) ,followed by respiratory system diseases(13 .8% ) and the musculoskeletal system diseases (11 .50% );The averaged score of 386 patients was 1 .76 ± 0 .78 , medication knowledge was at a general level;single factor analysis results showed that there was significant difference(P<0 .05) between rational drug-use and abuse of drugs among patients in number ,form of payment ,marital status ,income ,education level , taking drug knowledge lectures ,combined treatment .Multivariate Logistic regression analysis showed that education level ,partici-pation in lectures ,drug combination ,disease species had a significant impact on the rational drug use among patients with chronic disease(P<0 .05) .Conclusion The pharmaceutical knowledge that patients with chronic disease mastered is unsatisfactory ;and unreasonable behavior of medication is common scence .Education level ,participation in lectures ,drug combination ,the number of diseases have great influence on the rational use of drugs in patients with chronic diseases .A kind of effective pharmaceutical service mode should be established for patients with chronic diseases by clinical pharmacists .This is a very meaningful work for rational ad-ministration .

Effect of hyperin on acute liver injury in rats against oxidative stress-induced by CCl4 / 局解手术学杂志

Objective To study the protective effect of hyperin( Hyp) on the acute liver injury in rats induced by CCl4 . Methods The acute liver injury model was induced by CCl4 . The effect of Hyp on acute liver injury of rat liver histopathology was observed;and the impact of changes of homogenates total superoxide dismutase ( T-SOD) ,glutathione ( GSH) activity and malondialdehyde ( MDA) in liver were de-tected. Results The acute liver injury of tissue induced by CCl4,apparent pathological inflammation and fibrous tissue degeneration and necrosis were observed by HE staining;At the high doses of 60 mg/kg and medium doses of 30 mg/kg treated by Hyp,liver pathology changes was significantly obvious. The T-SOD,GSH activity of liver tissue was significantly increased in the groups of Hyp treatment,MDA content was significantly decreased,which related to the dosages. Conclusion In the rat model of acute liver injury induced by CCl4 . A better therapeu-tic effect of Hyp was shown,the mechanism may be related to its antioxidant activity.

Isolation of the drug-resistant Staphylococcus aureus strains from burn wound flora and analysis of norA genetic mutation / 中华创伤杂志

Objective To investigate the genetic mutation of the norA gene and its promotor from the wild-type drug-resistance Staphylococeus aureus(S.aureus)strains. Methods A total of 10 antibiotic-resistant S.aureus strains were isolated and screened from the burn wound for the sequencing and analysis of the nora gene and its promoter. Results There isolated 87 S.aureus strains from the burn wound flora,which were completely sensitive to vacomycin,highly sensitive to Quinupristin and Nitrofurantoin,but highly resistant to the other antibiotics,even up to91.7% of MRSA.There found the same point mutation(G→A) located at 1 349 sites of the norA gene coding region in all the S.aureus strains,saying that the amino acid was changed from Gly(glycin)to Asp(agpartic acid) in 291 sites.The resetpine reverse test showed that the MICs value of three antibiotics was lowered at various degrees in all 10strains.Conclusion NorA gene mutation is one of the mechanisms for antibiotic-resistance of S.aureus.

Drug Utilization in the Inpatients of Our Hospital During 2003～2007 / 中国药房

OBJECTIVE:To probe into the tendency and influencing factors of the drug expenses of the inpatients in our hospital.METHODS:The total drug expense,the antibiotic expense and its proportion in the total of the inpatients in our hospital were analyzed statistically in this retrospective study.RESULTS:During 2003～2007,the average daily total drug expense per inpatient was 371.77 yuan with average annual growth rate of 11.94%;the average daily antibiotics cost per inpatient was 110.35 yuan with average annual growth rate of 11.92%.Both the drug expense and antibiotic expense were correlated positively with the consumer price index (CPI).And the proportion of antibiotic expense in the total drug cost remained stable at about 29.68%.CONCLUSION:The average daily drug cost and antibiotic expenses per inpatient between 2003 and 2007 fluctuated yet with upward trend on the whole,and the proportion of antibiotic expense in the total drug cost remained stable.

Comprehensive Classified Management of Hospital Drug Storeroom / 中国药房

80% defined as category A,B,and C,respectively.Category A drugs were regarded as the focus of management,category B as the second focus of management,category C underwent general management,category D drugs were regarded as the focus in purchase.RESULTS:Hospital first-order drug storeroom and secondary drug storerooms classified their drugs into their own A,B,and C categories (category D was consistent).The consumption sum of category A drugs(about 20% of drugs) accounted for 60%;the consumption sum of category B drugs(about 20% of drugs) accounted for 20%;and the consumption sum of category C drugs(about 60% of drugs) plus that of small quantity of category D drugs accounted for 20%.CONCLUSION:This method can ensure drug supply and help maximize ec-onomical benefits with least human,material and financial resources.

Effects of Subinhibitory Concentration of Erythromycin on Adhesion of Clinical Isolated Staphylococcus Epidermidis / 中国药房

OBJECTIVE:To investigate the effect of subinhibitory concentration of erythromycin on adhesion of clinical isolated Staphylococcus(S.) epidermidis.METHODS:The subinhibitory concentration of erythromycin was determined based on the susceptibility test,and the representative strain Se.015 was treated with subinhibitory concentration of erythromycin.The optical density value determined by microtiter-plate assay was used to evaluate the effect of erythromycin on the adhesion of the representative strain Se.015,and electron microcopy was employed to observe the adhesion of Se.015 in samples with blank solvent served as control.RESULTS:Compared with control group,erythromycin(4 mg?L-1) group showed significantly higher optical density value(P