0.05) in tail flick test.MPE% in group MK was always higher than group M and descended more slowly than group M,especially from the d4 to d8(P0.05). Conclusion Ketamine could block the development of morphine tolerance partly due to its inhibition effect on pCREB protein.

Air ; Humans ; Workplace

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.

Objective In problem-based learning, students are often found difficult to con-struct medical knowledge systematically and transfer knowledge to solve new problems. In face of this challenge, this study aims to investigate the effect of visualization tool-supported online problem-based learning on medical students' clinical diagnostic expertise development. Methods A controlled study was conducted and 52 medical students were randomly assigned into experimental group (using visual-ization tool-supported online PBL environment for learning) and control group (using online PBL envi-ronment for learning without visualization tool support). Participants were asked to complete the diag-nostic analysis of three kidney problems according to the requirements of the learning environments and to provide feedback of online learning experience afterwards. Paired-sample t test and one-way analysis of vonriance were used to analyze both group's case 1 and case 3 on line learing scores. Results The results revealed that the experimental group had significant improvement in online learning performance [case 1: (1.47 ±0.54), case 3: (2.14 ±0.55), P=0.015], while the control group had no significant improvement [case 1:(1.57±0.67), case 3:(1.66±0.49), P=0.234]. Early performance of online learning and group factor had interative effects (F=7.266, P=0.013). Conclusions The findings suggest that visualization tool-supported online PBL environment can facilitate medical student clinical diagnostic expertise development effectively.

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals ; Biological Products ; CHO Cells ; Cricetulus ; Drug Interactions ; Fatty Acids, Monounsaturated ; pharmacology ; Flavonoids ; pharmacology ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Organic Anion Transporters ; genetics ; metabolism ; Rosuvastatin Calcium ; pharmacology ; Structure-Activity Relationship

Animals ; Comet Assay ; DNA Damage ; drug effects ; Lymphocytes ; drug effects ; Male ; Organometallic Compounds ; toxicity ; Rats

Objective To study the effect of euthyrox on blood lipids in patients with hypothyroidism throngh the meta analysis.Methods Patients with clinical hypothyroidism theated by euthyrox on blood lipid effect of randomized controlled trials were retried by Pubmed(2000/2014-07),EMbase (2000/2014-07),the Cochrane library(2014,7),the Chinese biomedical literature database(2000/2014-07),retrieved the time limit from January 2000 to July 2014.The paper were objective evaluated of the quality,Meta analysis with Rev Man 5.3 software system applicated by Cochrane collaboration.Results Euthyrox could significantly reduce cholesterol levels of hypothyroidism patients ,it was statistically significant difference(OR=0.63,95%CI:0.71 ~0.55,P<0.001);Euthyrox could significantly reduce triglyceride levels of hypothyroidism patients,difference was statistically significant(OR =0.29,95%CI:0.34 ~0.25,P <0.001 );Euthyrox could significantly reduce low-density lipoprotein cholesterol levels of hypothyroidism patients,it was statistically significant difference(OR=0.22,95%CI:0.30 ~0.14,P<0.001);euthyrox could obviously increase high-density lipoprotein cholesterol levels, it was statistically significant difference (OR =0.21, 95% CI:0.17 ~0.26, P <0.001 ). Conclusion Euthyrox could significantly reduce total cholesterol,triglyceride,low-density lipoprotein cholesterol(hdl-c)of hypothyroidism patients,and promote the synthesis of high-density lipoprotein cholesterol(hdl-c),could effectively promote the lipid metabolism,reduce blood fat level,prevent the happening of the disease of heart head blood-vessel hypothyroidism patients,have the guide meaning to clinical treatment.

Objective To observe the curative effects of applying laryngeal masks in the airway management in total laparoscopic hysterectomy in obese patients.Methods 60 cases of obese patients who underwent total laparoscopic hysterectomy were collected and were randomly divided into,the Endotracheal intubation (ET) group(n =30) and the laryngeal mask (LMA) group (n =30).The pre-operative co-existent diseases,applications of analgesia and intra-operative vital signs,the peak airway waves (Paw) 60min after pneumoperitoneum,blood gas;revival time;the incidences of complications were observed.Results 60min after pneumoperitoneum,MAP,HR,Paw and SpO2 values were:ET group:[(114.6 ± 22.4) mmHg,(108.2 ± 19.6) times/min,(25.4 ± 3.1) mmHg,(96.1 ± 1.2％)] LMA group:[(97.5 ±20.8)mmHg,(86.5 ±20.7) times/min,(22.6 ±3.7)mmHg,(98.9 ±0.8％)].The difference was statistically significant (P ＜ O.05);The blood gas analysis,PH,PaO2,PaCO2 and BE values are:ET group:[(7.34 ± 0.05),(177.5 ± 44.5) mmHg,(42.6 ± 6.1) mmHg,(-4.9 ± 0.8) mmol/L],LMA group:[(7.38 ± 0.05),(216.7 ± 46.6) mmHg,(38.4 ± 5.5) mmHg,(-3.1 ± 0.6) mmol/L].The difference was statistically significant (P ＜ 0.05);the status of complications:23 cases in ET group,accounting for 77％,10 cases in LMA group,accounting 30％,presenting significant differences (P ＜ 0.05).Conclusion The application of laryngeal masks in the airway management in total laparoscopic hysterectomy in obese patients facilitated the maintaining the stability of hemodynamics and blood gas,resulted in smooth post-anesthesia recovery and fewer complications.

OBJECTIVETo investigate the clinical effectiveness of sertraline hydrochloride combined with four-spot caress in the treatment of primary premature ejaculation (PE).

METHODSWe randomly assigned 90 primary PE patients to three groups of equal number. The patients in group A (aged [28.1 ± 5.2] yr and with a disease course of [3.1 ± 1.9] yr) were treated with oral sertraline hydrochloride at 50 mg qd, those in B (aged [27.8 ± 4.1] yr and with a disease course of [3.2 ± 2.0] yr) by four-spot caressing (caressing the tongue, breasts, and vulva prior to intercourse), and those in C (aged [27.1 ± 4.7] yr and with a disease course of [3.1 ± 2.0] yr) by the combination of oral sertraline hydrochloride and four-spot caressing, all for 12 weeks. Before and after 4, 8, and 12 weeks of treatment, we obtained the intravaginal ejaculatory latency time (IELT) and Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores and compared them among the three groups of patients.

RESULTSThe IELT was dramatically prolonged in groups A, B, and C after 4 weeks ([1.08 ± 0.29], [0.93 ± 0.28] and [1.21 ± 0.27] min), 8 weeks ([1.43 ± 0.30], [1.20 ± 0.33] and [1.72 ± 0.42] min) and 12 weeks of treatment ([2.12 ± 0.63], [1.90 ± 0.65] and [2.67 ± 0.82] min) as compared with the baseline ([0.63 ?0.14] , [0.60 ?0.14] and [0.62 ?0.11] min) (P < 0.05), even longer in group C than in A and B (P < 0.05). The CIPE-5 scores were markedly improved in groups A, B and C after 4 weeks ([15.17 ± 1.74], [14.57 ± 1.94] and [15.60 ± 1.63] min), 8 weeks ([17.13 ± 1.63], [16.37 ± 1.97] and [18.00 ± 1.05] min) and 12 weeks of intervention ([18.93 ± 1.57], [18.53 ± 1.67] and [20.00 ± 1.46] min ) as compared with the baseline ([12.57 ± 2.05], [13.20 ± 2.51] and [13.07 ± 2.01] min) (P < 0.05), even higher in group C than in A and B (P < 0.05).

CONCLUSIONSertraline hydrochloride combined with four-spot caressing, with its definite efficacy and rare adverse reactions, deserves wide clinical application in the treatment of primary PE.

Adult ; Coitus ; Ejaculation ; Female ; Humans ; Male ; Premature Ejaculation ; drug therapy ; Sertraline ; therapeutic use ; Young Adult