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OBJECTIVE：To study the anti-tumor effect of artemether （ARM）self-microemulsifying drug delivery system （SMEDDS） on human glioma subcutaneously transplanted model mice. METHODS ：Human glioma cell line SHG 44 was inoculated and passed on to establish subcutaneous transplanted tumor model of nude mice. At the 5th，10th，15th，20th and 25th day after inoculation ，the tumor tissue volume was measured and the growth curve was drawn to confirm the initial stage of rapid tumor proliferation. Thirty nude mice was collected to establish subeutaneously transplanted tumor nude model ，and then divided into control group （normal saline ），ARM suspension group [ 60 mg/（kg·d）]，ARM-SMEDDS low-dose ，medium-dose and high-dose groups [ 10，20，30 mg/（kg·d）] at the initial stage of rapid tumor proliferation. They were given normal saline and relevant solution intragastrically once a day ，for consecutive 30 d. The weight change and general sibuation of mice were recorded. The change of tumor volume was determined and relative tumor proliferation rate was calculated. RESULTS ：The subcutaneously transplanted tumor tissue entered the initial stage of rapid tumor proliferation from the 10th day after transplantation. The general situation was normal ，and there was no obvious abnormal reaction in mice of each group during treatment. Since 10th day of administration，tumor tissue volume of mice in ARM-SMEDDS groups were shortened significantly than control group （P＜0.05）. At 15th day of administration ，tumor volume of mice in ARM-SMEDDS groups were shortened significantly than ARM suspension group（P＜0.05）. After last administration ，relative tumor proliferation rates of mice in ARM-SMEDDS groups were decreased significantly，compared with ARM suspension group （P＜0.05）. CONCLUSIONS ：ARM-SMEDDS show significant inhibitory effect on the proliferation of human glioma ，and are better than suspension with higher dosage.
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OBJECTIVE:To provide reference for improving the teaching quality of pharmaceutical analysis course. METH-ODS:WeChat public platform was registered firstly,and supplement teaching was provided before class,during class and after class. RESULTS:WeChat public platform named Pharmaceutical Analysis of Chongqing Medical and Pharmaceutical College was registered and included 2 first-level-modules of"excellent resource"and"learning interaction",and 6 second-level-modules of"classic courseware""pre-course lesson plan""classic video""classroom exercises""question answering""classic case". Before class, students could preview through the platform;during class,the teachers could review teaching according to the platform;after class,the teachers could test students'learning results and answer questions for students,and students could consolidate classroom knowledge. Post-course effect evaluation showed that there was statistical significance in pass rate of student's grade between teach-ing reform class and control class (P<0.05). And the students of teaching reform class had good satisfactory degree (87.07%). CONCLUSIONS:WeChat mobile learning model supplements pharmaceutical analysis course,improves students'enthusiasm for learning and students,academic records. Students are satisfied with it. It can provide reference for improving the teaching quality of the course.
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Objective To explore the effect of navigation assisted surgery system in the medical teaching in the department of neurosurgery. Method From May 4 of 2015 to June 3 of 2015, 51 medical undergraduates of clinical medicine in the Second Affiliated Hospital of Xi'an Jiaotong University were ran-domly divided into experiment group (navigation assisted surgical technique system teaching, n=25) and traditional group (traditional teaching, n=26). Practical effect of the different modes was evaluated by ques-tionnaire and examination results. Data were analyzed by SPSS 20.0. Enumeration data were compared between groups using chi square test or t test. Result After the teaching, the theoretical results of the experimental group and the control group were (83.05 ± 6.03) and (74.32 ± 7.12), and the difference was statistically significant (t=4.96, P=0.005). Clinical skills scores were (89.43 ± 5.12) and (81.11 ± 8.02), and the difference was statistically significant (t=2.91, P=0.029). The questionnaire showed that the experimental group students'!satisfaction degree to their own teaching method was better than that of control group (P<0.05). Conclusion Compared with the traditional teaching, the navigation assisted neurosurgical operation has obvious advantages. It can improve students'!enthusiasm for learning the professional knowledge and skills in neurosurgery, stimulate students'!learning interest and improve students'!test scores.
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OBJECTIVE:To study relative bioavailability of dauricine self-microemulsifying drug delivery system (SMEDDS) in rats. METHODS:12 rats were randomly divided into dauricine SMEDDS group (20 mg/kg) and dauricine solution group (50 mg/kg),6 rats in each group. They were given relevant medicine intragastrically. Then,0.3 ml plasma was collected from orbital venous plexus before medication and 0.167,0.333,0.5,0.75,1,2,4,8,12,24,36 h after medication. The plasma concentration of da- uricine was determined by HPLC-MS/MS,and DAS 3.0 was used to calculate pharmacokinetic parameters and evaluate the relative bioavailability of dauricine with dauricine SMEDDS. RESULTS:The linear range of dauricine in plasma were 2.12-424 ng/ml (r=0.999 9);RSDs of intra-day and inter-day were all lower than 10%. Pharmacokinetic parameters of dauricine solution and dau-ricine SMEDDS were that cmax were(126.3±37.4)ng/ml and(179.6±51.5)ng/ml;t1/2 were(11.48±4.58)and(21.79±6.59)h;AUC0-t were (1 963.5±638.3)ng·h/ml and(2 535.8±739.5)ng·h/ml;AUC0-∞ were(2 256.3±703.5)ng·h/ml and(2 854.6± 768.7)ng·h/ml,respectively. The relative bioavailability of dauricine SMEDDS were 323% and 316% by calculating with AUC0-t and AUC0-∞,respectively. CONCLUSIONS:Intragastric administration of dauricine SMEDDS can improve relative bioavailability of dauricine significantly.
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Objective To explore the clinical effect of amiodarone combine with irbesartan on arrhythmia patients with heart failure ,to observe its effect on cardiac function and its mechanism .Methods 124 patients with chronic heart failure combine with arrhythmia were selected in the hospital from September 2013 to November 2014 ,they were randomly divided into the control group and the observation group ,62 patients in each group .The control group was treated with amiodarone on the basis of routine thera-py ,the observation group was treated with amiodarone combine with irbesartan .The clinical efficacy of the two groups were as-sessed after treated 6 months ,the maintenance of sinus rhythm were observed after 1 ,3 and 6 months .By ultrasound heartbeat to assess heart function :cardiac stroke volume (SV) ,left ventricular ejection fraction (LVEF) ,left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) ,and to observe the adverse reactions .Results The efficiency rate of the observation group was 88 .71% (55/62) ,higher than that of the control group 62 .90% (39/62) ,the difference was statistically significant (P 0 .05) .Conclusion Amiodarone combine with irbesartan has good clinical efficacy in the treatment of heart failure combine with arrhythmia ,the maintenance rate of sinus rhythm can be significantly enhanced ,and improve heart function ,it has a higher se-curity .
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Objective To study the influence of valsartan combined with indapamide on the UmAlb level and blood pressure in patients with hypertension and diabetes mellitus.Methods 90 patients with hypertension and diabetes mellitus were selected and randomly divided into three groups by number table.30 cases of the control group A were treated with indapamide,30 cases of the control group B were treated with valsartan,30 cases of the observa-tion group were treated with indapamide combined with valsartan.After treatment,the clinical parameters and effect of the three groups were compared.Results After treatment,the systolic blood pressure and diastolic blood pressure of the three groups were decreased(all P <0.05),and the observation group decreased obviously(all P <0.05).The total effective rate of the observation group was 96.7%,which was higher than 86.6% of the control group A and 83.3% of the control group B(χ2 =4.1 2,4.22,all P <0.05).Conclusion In the treatment of hypertension and diabetes,the antihypertensive effect of indapamide combined with valsartan is obvious and can protect the renal func-tion,which should be promoted in clinical use.
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This study is to examine the effects of NNIspm-mediated cellular senescence of HepG2 cells and elucidate its potential molecular mechanism. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution, intracellular fluorescence intensity and accumulation of intracellular reactive oxygen species (ROS) were detected by high content screening (HCS). Protein expression was detected by Western blotting. Polyamines content was analyzed by high performance liquid chromatography (HPLC). The results demonstrated that NNIspm significantly induced HepG2 cells senescence. This effect was due to the decrease of intracellular polyamines, the arrest at G0/G1 phase and an increase of ROS level. The molecular senescence marker p21 increased significantly after NNIspm treatment. In contrast, the protein expressions of Cyclin E and CDK2 were obvious down-regulation. The results indicated that cellular senescence induced by NNIspm was one of its antitumor mechanisms.
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This paper is to report the study of resveratrol-induced apoptosis and its mechanisms in MCF-7 cells. MTT assay was performed to assess the cytotoxicity of resveratrol on MCF-7 cells. Hoechst 33258 staining was used to observe cellular morphologic changes in apoptosis. Apoptosis was measured by flow cytometric analysis and the protein expression was examined by Western blotting analysis. The results indicated that resveratrol could inhibit MCF-7 cell growth in a time- and concentration-dependent manner. Remarkable morphologic changes in the cells after 60 micromol L(-1) resveratrol treatment, including cell nuclear shrinkage, DNA condensation and apoptotic bodies, were observed by Hoechst 33258 staining. Resveratrol could induce apoptosis and activate p38 and p53 in a time dependent manner in MCF-7 cells. In addition, the cell growth inhibitory ratio and the apoptotic ratio of resveratrol-treated group decreased markedly by the p38 MAPK inhibitor SB203580 or p53 inhibitor pifithrin-alpha. Further experiments confirmed that resveratrol-induced p53 activation was reduced by SB203580 whereas the activation of p38 was not affected by pifithrin-alpha. In conclusion, resveratrol induced apoptosis in MCF-7 cells could be through activating p38-p53 signal pathway.
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The objective of this study is to examine the effects of ANISpm, a novel polyamine naphthalimide conjugate, with acetylsalicylic acid against hepatocellular carcinoma in vivo and in vitro and elucidate its potential molecular mechanism. The proliferation inhibition was detected by MTT assay. Cell apoptosis, intracellular fluorescence intensity and mitochondrial membrane potential (MMP) were detected by high content screening (HCS) analysis. Polyamines content was analyzed by reverse-phase high performance liquid chromatography Protein expression levels were quantified by Western blotting assay. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis in HepG2 cells and H22 hepatoma cells, which was mediated by enhanced ANISpm uptake via up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) and depression of intracellular polyamine. Furthermore, this synergistic apoptosis was involved in mitochondria and death-receptor signal pathway. All these findings demonstrated that the combination treatment with acetylsalicylic acid and ANISpm resulted in synergistic antitumor effects on hepatoma cells. Thus, combination therapy with these agents may be useful as a potential template for the development of better chemotherapeutic strategy against hepatoma.
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Aim To investigate the apoptotic mechanism and polyamine transporter recognition of 3-nitro-naphthalimide norspermine conjugate (NNINspm),a novel naphthalimide-polyamine conjugate, in HepG2 cells.Methods The cytotoxicity of NNINspm was assessed by MTT assay.Cell cycle distribution and apoptosis were measured by flow cytometry.The protein expression of cytochrome C,14-3-3,Bad,Bcl-xL,mTOR,p70S6K,Cdk4,p27~(kip1),Akt,Caspase-3,Caspase-9 was evaluated by Western blot.The translocation of Akt was detected by high content screening (HCS) analysis.Results NNINspm induced HepG2 cells apoptosis via Akt dephosphorylation and then triggered a series of signal events, such as Bad dephosphorylation, dissociation of 14-3-3 and Bad, and then binding to Bcl-xL,which finally resulted in mitochondrial disruption,cytochrome c release and caspase cascade activation.Furthermore,the NNINspm-mediated cell cycle arrest was due to mTOR and p70S6K dephosphorylation,Cdk4 down-regulation and p27~(kip1) up-regulation.Conclusion NNINspm induces HepG2 cell apoptosis via PI_3K/Akt signal pathway.
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In the present study, the apoptotic mechanism and polyamine transporter recognition of WJH-6, a novel polyamine conjugate, were investigated in K562 and HL-60 cells. The cytotoxicity of WJH-6 was assessed by MTT assay; cell cycle distribution and apoptosis were measured by flow cytometry; the protein expression of Caspase-3, Caspase-8, Caspase-9, Bid and mitochondrial membrane potential (MMP) were evaluated by high content screening (HCS) analysis; the protein expression of cytochrome c was measured by Western blotting. The results showed that WJH-6 could be recognized and transported by polyamine transporter (PAT). Furthermore, WJH-6 was able to inhibit K562 and HL-60 cells proliferation and induce apoptosis. This apoptotic effect was relative to MMP loss, cytochrome c release from mitochondria to cytoplasm and the activation of Caspase-8, Caspase-9, Caspase-3 and Bid. These results suggested that WJH-6-induced K562 and HL-60 cells apoptosis was related with mitochondrial damage.
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Five eyes of acute retinal necrosis(ARN) with multiple retinal breaks and retinal detachment were treated by closed vetrectomy combined with encircling buckle, gas/fluid exchange, endolaser and cryotherapy. After operation, the detached retinas reattached in 4 eyes, and among them the visual acuity was 0.2 in 1 eye, and better than 0.05 in 3 eyes. The follow-up duration in 5 eyes was from 6 to 18 months and recurrent retinal detachment was found in one eye.
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Objective: To study percutaneous absorption of cinnamic acid and the effect of some common enhancers and pH value on it. Methods: Drug permeation tests were performed in K-C two-compartment diffusion cell through excised mice skin. Samples were collected from the receiver compartment, cinnamic acid concentration in samples was determined by HPLC. Results: Cinnamic acid could penetrate through excised mice skin. The permeability coefficient of cinnamic acid rose as its concentration increased. Cinnamic acid consisted of 20% ethanol, 30% ethanol and 3% Azone had high penetrating power. Conclusion: The research will provide experimental data for skin administration of Chinese medicine holding cinnamic acid.