Glycogen synthase kinase-3β is a kind of conserved serine/threonine protein kinase that has been generally found in eukaryotic cells, whose activity is regulated by a variety of kinases and signaling pathways.The biological effects of glycogen synthase kinase-3β are closely related to the growth, proliferation, apoptosis, migration and metastasis of tumor cells, which is a key target for tumor therapy.Studies have found that in different types of tumors, glycogen synthase kinase-3β has two distinct effects on tumors : suppression and promotion .By reviewing the relevant literatures,the role of glycogen synthase kinase-3β on different types of tumors as well as its molecular mechanism was studied, in order to provide treatment strategies for tumor therapy by targeting glycogen synthase kinase-3β.
Objective To observe the effects of salidroside regulating glucose metabolism in type 2 diabetic mice,then to explore the molecular mechanism. Methods Type 2 diabetes model was induced by feeding high-fat diet and intraperitoneal injecting STZ to male C56BL/6J mice,then the glucose related indexes,micro RNA-370 levels in the serum and liver tissue and the expression of gluconeogenesis key protein (G6Pase and PEPCK) in the liver tissue to observe the treatment effects of salidroside on type 2 diabetic-caused gluose metabolic disorder.In cell test,we isolated primary hepatocytes,then silenced or over-expressed micro RNA-370 in mouse primary hepatocytes to observe the molecular mechanism of glucose metabolic regulation of the micro RNA-370 and salidroside. Results Treated with salidroside 40,80 and 160 mg·kg-1,the results showed that compared with the model control group,the glucose related indexes were all improved significantly.The relative expression levels of micro RNA-370 in serum and liver,and that of PEPCK and G6Pase all reduced in different degrees,dose-dependently.The changes of middle and high dose group decreased significantly(P<0.05),that of low dose group had a decreasing trend but no statistically significant.In the cell test,compared with the normal control group,salidroside alone group and micro RNA-370 inhibitor group were able to reduce the protein expression level of PEPCK and G6Pase(P<0.05),micro RNA-370mimic alone group can significantly increase the protein expression level of PEPCK and G6Pase(P<0.05),compared with the micro RNA-370mimic alone group,combining micro RNA-370 mimic and salidroside can significantly reverse the increasing caused by micro RNA-370 mimic alone(P<0.05). Conclusion Our research found that salidroside can improve glucose metabolism disorder in type 2 diabetic mice,and at least in part,through the suppression of micro RNA-370 expression for the first time.
Objective To investigate the toxicokinetic properties of ginkgolide B (GB) injection after single or repeated administration by intravenous drip in Beagle dogs and to provide evidence for its rational use. Methods Beagle dogs were randomly divided into three groups, and received GB injection at big, medium and small doses of 80, 20 and 5 mg·kg-1, respectively, by iv drip for 30 min per day and for 6 consecutive days per week for up to 91 days.The blood samples of Beagle dogs were drawn at different time points on the first and last day of administration,and concentrations in plasma were detected by GC-MS method.Toxicokinetic parameters were calculated by DAS pharmacokinetic software and statistically analyzed by SPSS 11.5 software. Results The elimination half-life (t1/2β) of GB at single dose of 5, 20, 80 mg·kg-1 were (110.2±32.6),(115.4±12.8),(98.6±26.8) min, respectively.The AUC0-t were (61.1±7.4), (348.6±90.5), (2 046.2±356.4) mg·L-1·min,respectively.The t1/2β of GB at mutiple doses of 5,20,80 mg·kg-1 on the 91rd day were (117.9±28.0),(118.2±17.0),(120.5±49.4) min,respectively.The AUC0-t were (67.9±14.9), (218.3±31.8), (1 986.4±426.6) mg·L-1·min, respectively.There was no significant difference in main toxicokinetic parameters including t1/2β among the single or repeated dosage groups, but AUC0-t and Cmax increased proportionally with doses. Conclusion The curves of single and repeated intravenous drip of GB injection in beagle dogs were in line with the two atrioventricular model, with linear dynamic characteristics and there was no accumulation of repeated drug delivery in the body.
Objective To investigate the protective effects of iguratimod on systemic lupus erythematosus model mice. Methods A total of 30 female BALB/c mice were randomly divided into blank control group,model control group and iguratimod drug intervention group,with 10 mice in each group.The blank control group was given saline by intraperitoneal injection intervention group.The model control group and iguratimod intervention group were given 0.5 mL of pristane, Then the drug intervention group began to be fed with iguratimod 6.5 mg·kg-1·d-1 from the next day.After 7 months of feeding,the serum autoantibody (anti nuclear antibody,anti ds-DNA antibody,anti RNP/sm antibody) ,the level of urine protein, serum urea nitrogen and serum creatinine,as well as the renal pathological changes of the three groups were detected and compared. Results Serum anti nuclear antibody,anti ds-DNA antibody and anti RNP/sm antibody levels of the drug intervention group were significantly lower than those of the model control group (P<0.05);Positive rate of urine protein,serum urea nitrogen,serum creatinine of the drug intervention group were significantly lower than those of the model control group (P<0.05).while the renal pathological change of this group is not obvious. Conclusion Iguratimod can inhibit the occurrence of serum antibody in a certain extent,improve the urine protein,serum urea and serum creatinine level of mouse model with systemic lupus erythematosus,which has protective effects on systemic lupus erythematosus.
Objective To explore the effects of immunoglobulin G on tumor necrosis factor (TNF-α) secretion of human peripheral blood mononuclear cells (PBMCs) in type 2 diabetes mellitus complicated with Alzheimer’s disease (AD). Methods A total of 20 cases were chosen in each group from patients with type 2 diabetes mellitus complicated with Alzheimer’s disease and patients with type 2 diabetes mellitusm .PBMCs were isolated using density gradient centrifugation method and incubated with phytohemagglutinin (PHA) as well as immunoglobulin G extracted from blood serum of the patients with type 2 diabetes mellitus.TNF-α concentration in supernatant was measured by enzyme linked immunosorbent assay (ELISA). Results TNF-α concentration in supernatant of PBMCs was significantly increased in type 2 diabetes mellitus complicated with AD compared with that in type 2 diabetes mellitus (P<0.01).IgG further increased TNF-α concentration in type 2 diabetes mellitus and type 2 diabetes mellitus complicated with AD (P<0.01). Conclusion IgG extracted from the serum of type 2 diabetes mellitus patients can promote TNF-α secretion in PBMCs of type 2 diabetes mellitus complicated with AD.Immunity injury could play a role in the development of type 2 diabetes mellitus complicated with AD by promoting inflammatory reaction.
Objective To investigate the effects of edaravone on sympathetic remodeling and ventricular arrhythmias in rats myocardial infarction model. Methods A total of 65 rats were randomly divided into the sham operation group (n=15), model control group(n=25), and edaravone group(n=25).Myocardial infarction model was established by ligation of the left anterior descending coronary artery.The edaravone group was injected intraperitoneally with edaravone (3 mg·kg-1·d-1), while the model control group and sham groups were injected with 0.9% sodium chloride soution.7 days after operation,the hemodynamics were detected and then ventricular arrhythmia at the peri-infarct zones was induced.After these studies,the expression of the signaling pathway NF-κB/p65, IκBα, p-IкBα at the peri-infarct zones were examined by western blotting, while the expression of GAP43 and TH were examined by immunohistochemical method. Results Compared with the sham group, the inducibility of ventricular arrhythmia after MI was increased, the expression of GAP43 and TH were increased significantly (P<0.05), the signaling pathway of NF-κB was activated, while compared with the model control group, all of the above were suppressed by edaravone (P<0.05). Conclusion Edaravone inhibits sympathetic remodeling and ventricular arrhythmias after myocardial infarction, the effects of which may be partly related to the inhibition of NF-κB pathway, (P<0.05).
The pulmonary drug delivery system is a new drug delivery system developed in recent decade.Its composition and mode of administration are obviously different from those of the general preparation.The advantages of pulmonary drug delivery system include high local drug concentration,no first pass effect and fast drug absorption.Currently,it has become an important means of treating lung diseases and promoting the drug absorption of macromolecules.The drug categories,excipients,inhalation devices and clinical application of pulmonary drug administration were analysed by literature reviews.Furthermore,the research progress and characteristics of pulmonary drug delivery system in recent years were also summarized,which provide reference for further study of pulmonary drug delivery.
Inhaled drug was delivered through the oral and nasal cavities,which can avoid the liver first pass effect and nervous system barriers.Inhaled drugs can directly reach the disease site, which play a critical role in the treatment of respiratory diseases,infectious diseases,endocrine system diseases,nervous system diseases,tumor diseases,surgical perioperative respiratory tract management,preventive medicine and so on.Furthermore, as a non-invasive drug delivery method, inhalation has many advantages such as high bioavailability, good stability, and targeted binding to lesion site, low systemic drug exposure, low side effects and easily acceptance.It will play an important role in the treatment of systemic diseases with whole body.In this paper, the research progress in the prevention and treatment of diseases in various systems by inhalation administration is reviewed.in order to explore the value of inhalation administration in the treatment of diseases, to improve the awareness of medical nursing staff on the way of inhalation treatment and to make patients have more benefit.
Objective To evaluate the correlation between carbapenem consumption and resistance to carbapenems among the frequent gram-negative bacteria and provide the basis for rational use of drugs. Methods Retrospective review was used to calculate the DDDs of carbapenems(impenem and meropenem) per 100 persons per day from the year of 2004 to 2016 and resistant rate of the frequent gram-negative bacteria (Acinetobacter baumannii,Pseudomonas aeruginosa,Klebsiella pneumoniae,and Escherichia coli).The correlation of drug usage and resistance were analyzed by SPSS 17.0 software. Results The study demonstrated that carbapenem usage was strongly correlated with imipenem and meropenem-resistant Acinetobacter baumannii,Klebsiella pneumoniae,while has no significant correlation with Pseudomonas aeruginosa,Escherichia coli. Conclusion The growing problem of gram-negative bacteria resistant to carbapenems was strongly related to the high consumption of carbapenems.It also suggested that optimum antibiotic use was necessary to alleviate the threat posed by resistant microorganisms at the hospital level.
Objective To apply intervention of integrated pharmaceutical care (IPC) for asthma-COPD overlap syndrome patients,so as to reduce the side effects of drugs,enhance medication compliance,promote reasonable drug application,cut down the medical expenses in ACOS patients. Methods A total of 60 ACOS patients were randomly divided into IPC group (group A) (n=34) and contrast group (group B) (n=26).The patients in group A were given IPC measurements such as nosocomial guidance,classroom teaching,regular follow-up,life coaching and psychological advice.While the patients in group B were not given any intervention measures. Results In group A,patients’ awareness rate of action and side-effects of drugs were obviously increased;Knowledges of inhalation preparation were greatly improved;the ratio of ADRs was significantly reduced;The FEV1 and the value added of FEV1 was dramatically improved.Furthermore,the differences showed statistical significance as compared with group B (P<0.05).Total medical costs and anti-bacterial drug costs per year were significantly lower in group A than group B. Conclusion IPC is beneficial to enhance drug compliance,promote reasonable drug application and bring down the medical expenses in ACOS patients.
Objective To investigate the preemptive analgesic effect and safety of paracoxib sodium in patients undergoing endoscopic submucosal dissection(ESD). Methods A total of 80 ASA I or II patients aged 35-65 years undergoing ESD under general anesthesia were randomized into two groups(n=40 each):parecoxib sodium group (group B) was received intravenous parecoxib sodium 40 mg (in 5 mL 0.9% sodium chloride solution) 10 min before anesthesia induction and control group(group A)was received 0.9% sodium chloride solution 5 mL instead of parecoxib sodium.At the end of operation,patients in both groups were received 5 mg of dezocine.Blood samples were analyzed for PT,TT,APTT,Fib,PLT and PAgT before induction of anesthesia,at 30 min and 120 min after operation.Patients’Visual analogue scale(VAS),Numeric sedation scale(NSS),and adverse reactions were recorded at the end of the operation,2,4 and 6 h after operation. Results Compared with those before parecoxib sodium administration,the fibrinogen concentration and PAgT were significantly higher in group B at 30 min after the intravenous injection of parecoxib sodium(P<0.05),while there was no significant difference in PT,TT,APTT and platelet count between group B and group A(P>0.05).VAS at the end of operation,2,4 and 6 h after operation were lower in group B(P<0.05),and the patients were more satisfied in group B(P<0.05). Conclusion Parecoxib could temporarily enhance blood coagulation in patients undergoing ESD and could offer safe and effective analgesia.
Resveratrol,a naturally occurring polyphenol and phytoalexin,has received significantly attention in recent years due to its vast therapeutic effects including anticancer,antioxidant and anti-inflammatory effects,etc.However,poor pharmacokinetic properties such as low aqueous solubility, low photo-stability and extensive first pass metabolism result in poor bioavailability, which hindering its immense potential.A number of theoretical solutions have been developed to improve the bioavailability of resveratrol.This review enumerates the physicochemical and pharmacokinetic properties that affect resveratrol bioavailability, describes formulations tested for resveratrol administration and identifies future opportunities for resveratrol delivery.
Objective To establish a quality standard of yinqiao xiaozhen mixture. Methods Preparation of Forsythia,Arctium lappa L.,and Honeysuckle were identified by TLC method.The concentration of baicalin in yinqiao xiaozhen mixture was determined by HPLC method. Results The qualitative identification method can detect Forsythia,Arctium lappa L.,and Honeysuckle.TLC spots were clear.TLC method has strong specificity.The linear range of baicalin was 0.122 5-1.531 2 μg,r=0.999 9,the average sample recovery rate was 99.42%,RSD was 2.19%,respectively. Conclusion The method is simple,accurate and repeatable,which can be used for quality control of yinqiao xiaozhen mixture.
Objective To establish a quality standard of huangqi baoxin mixture and improve its quality control system. Methods The qualitative analysis of Astragalus membranaceus,Salvia miltiorrhiza,Forsythia,and Angelica were performed by TLC.The content determination of astragaloside Ⅳ in the huangqi baoxin mixture was conducted by HPLC-ELSD. Results Astragalus membranaceus,Salvia miltiorrhiza,Forsythia,and Angelica in the huangqi baoxin mixture could be accurately identified by TLC.The linear range of astragaloside Ⅳ was 1.224-10.20 μg (r=0.999 5).RSDs of precision,stability,and reproducibility tests were lower than 3.0%;the recovery was 96.2%-102.9% with RSD at 2.20% (n=6). Conclusion The established quantitative method is simple,accurate,and reliable with high specificity which can be used to control the quality of huangqi baoxin mixture.
Objective To study the best formulation and technology of quercetin-loaded polylactic- co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (QPTN) with QT as model drug and PLGA-TPGS as polymer materials by orthogonal tests,and to investigate the in vitro stability of QPTN. Methods To ensure the best formulation and technology for preparing QPTN,single-factor test was established to determine the influence of the ratio of quercetin to PLGA-TPGS,the concentration of TPGS as emulsifiers,the ultrasonic power and ultrasonic time to the particle size,drug loading (DL) and entrapment efficiency (EE) .According to single-factor test,the factor levels of nanoparticles were set to select the best prescription and technology of QPTN by orthogonal test.The stability of QPTN was examined using the effecting factor test,acceleration test and long-term test. Results The best formulation and technology of QPTN was that the ratio of quercetin to PLGA-TPGS was 3:10 (W:W) with 0.05% TPGS as emulsifier,the mixed solution was sonicated for 6 min at 200 W.The average particle size,DL and EE of QPTN prepared under the conditions described above were (155.4±2.7) nm,(21.6±1.5)% and (93.7±2.9)% (n=6),respectively.In the in vitro stability test,QPTN showed a good stability at high temperature,high humidity and strong light condition. Conclusion The best formulation and preparation technology of QPTN was selected.QPTN got small particle size,high DL and EE,and good in vitro stability.
Objective To optimize the pretreatment conditions in the detection of selenium from hugan tablets. Methods The main influential factors of pretreatment conditions included concentration of hydrochloric acid,time in water bath and concentration of potassium ferricyanide solution.The extraction effect was evaluated with the content of selenium.Pretreatment conditions were optimized by central composite design-response surface methodology. Results The best pretreatment conditions was 6 mol·L-1 hydrochloric acid,30 minutes of bathing in water bath,20%potassium ferricyanide solution. Conclusion The central composite design-response surface methodology is highly predictive,reasonable and feasible.
Objective To establish a UPLC-MS/MS method for simultaneous determination of 19 chemical drugs in Traditional Chinese Medicines and health products for treating rhinitis. Methods Separation was performed on Waters ACQUITY UPLC BEH-C18 column (2.1 mm×100 mm,1.7 μm) with 0.1% formic acid acetonitrile solution and 0.1% formic acid aqueous solution as the mobile phase by gradient elution.The flow rate was 0.3 mL·min-1.The column temperature was set at 35 ℃.The detection was performed by the positive ion electrospray ionization (ESI+) under multiple reactions monitoring (MRM) mode. Results The linear relationships of 19 chemical drugs were good in respective ranges with correlation coefficients higher than 0.995.The average recoveries of the low,medium,and high level were in the range of 84.9%-111.1%,and the RSDs were less than 5.2%.The limits of detection (LOD) and the limits of quantitation (LOQ) were in the range of 0.03-0.78 ng·mL-1 and 0.13-1.82 ng·mL-1,respectively. Conclusion The method is convenient,rapid,accurate,and sensitive,which can be used for the determination of chemical drugs added illegally in traditional Chinese medicines and health products for treating rhinitis.
Objective To systematically evaluate the efficacy and safety of magnesium isoglycyrrhizinate (MgIG) in the treatment of viral hepatitis based on clinical studies. Methods Searches were conducted in the databases of Cochrane,PubMed,Science Direct,CNKI,CMCI and Wanfang (until Dec.2016 since database setup) to identify randomized controlled trials (RCTs) evaluating clinical effects of MgIG vs Compound Glycyrrhizin (CG).Literatures according to inclusion and exclusion criteria were screened.All meta-analysises were conducted with RevMan version 5.3. Results A total of 3 790 patients enrolled in 32 studies were included in the meta-analysis.Firstly,the comparison of curative effect in two groups favors MgIG for the treatment of viral hepatitis[OR=2.87,95% CI=(2.29,3.61),P<0.000 01] .Secondly,MgIG showed statistically significant benefit in reducing ALT [MD=-17.27,95%CI=(-28.87,-5.66),P=0.004],AST [MD=-14.18,95%CI=(-18.29,-10.08),P<0.000 01] and T-BiL[MD=-4.53,95%CI=(-6.38,-2.68),P<0.000 01].Lastly,comparative trials demonstrated a significant safety advantage of MgIG over CG [OR= 0.29,95%CI=(0.19,0.44),P<0.000 01]. Conclusion MgIG has a significant beneficial effect for the treatment of viral hepatitis by means of both decreasing transaminase and normalizing liver function.Furthermore,it is worth for the application in clinical use with less adverse drug reactions.
Objective To systematically review the efficacy and safety of tandospirone in the treatment of generalized anxiety disorder (GAD) and to provide evidence-based references for clinic. Methods Databases include PubMed,EMbase,The Cochrane Library,CBM,CNKI,VIP and Wanfang Data were electronically searched from the inception to November 2016,to collect randomized controlled trials(RCTs)about the tandospirone citrate in the treatment of generalized anxiety disorder.Meta-analysis was performed by RevMan5.3 software after data extraction and quality evaluation. Results A total of 5 RCTs involving 500 patients were included.The results of Meta-analysis showed no significant differences in the Hamilton Anxiety Scale (HAMA) score between experimental group and control group[MD=0.47,95%CI(-0.51,1.45),P=0.34];and there was no significant differences of total effective rate between experimental group and control group [OR=1.03,95%CI(0.64,1.67),P=0.90] .The incidence of adverse reactions in experimental group was significantly lower than that of control group,the difference was statistically significant[OR=0.65,95%CI(0.44,0.95),P=0.03]. Conclusion Tandospirone citrate,as a new type of non-BZDs of antianxiety drug,shows exact clinical curative effect in the treatment of generalized anxiety disorder with mild adverse reaction and good safety.