1.Preparation of cell penetrating peptide TAT and cleavable PEGco-modified liposomes loaded with paclitaxel and its in vitro apoptosis assay.
Han FU ; Guan-Lian HU ; Qin HE
Acta Pharmaceutica Sinica 2014;49(7):1054-1061
The preparation method, serum stability, efficiency of cellular uptake and apoptosis induction of the cell penetrating peptide TAT and cleavable PEG co-modified liposomes loaded with paclitaxel (C-TAT-Lipo) were investigated. The best preparation procedure was performed by orthogonal test based on single factor screening method. First, the paclitaxel (PTX)-loaded liposomes were prepared by filming-rehydration method, evaluated with entrapment efficiency and polydispersity index. The morphology of C-TAT-Lipo was characterized by transmission electron microscopy. Turbidity variations were monitored in the presence of fetal bovine serum (FBS) to evaluate the serum stability of the liposomes developed here. Next, the efficiency of cellular uptake of different Rho-PE-labeled liposomes on B16F1 cells in vitro was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry. The quantitative analysis of apoptosis induced by different PTX-loaded liposomes was performed by Annexin V-FITC/PI double staining. The optimal formulation was as follows: Chol : lipid: 1 : 8 (molar ratio); drug : lipid: 1 : 40 (mass ratio); lipid concentration: 3 mmol x L(-1); temperature of hydration: 25 degrees C. The mean size and polydispersity index of C-TAT-Lipo were about (97.97 +/- 3.68) nm and 0.196 +/- 0.037, the zeta potential was (-0.89 +/- 0.45) mV, the entrapment efficiency of paclitaxel was (90.16 +/- 1.53)%. The particle sizes did not exhibit significant variations in 50% FBS over 24 h at 37 degrees C. The efficiency of cellular uptake of the C-TAT-Lipo increased 1.40 fold following the cleavage of PEG. Apoptosis analysis showed 59.3% increase of the apoptosis and necrosis profile of C-TAT-Lipo after the detachment of PEG shells, which was markedly higher than that of N-TAT-LP with or without glutathione and SL, respectively. The results indicate that the C-TAT-Lipo is successfully prepared by filming-rehydration method and shows significant antitumor activities.
Animals
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Annexin A5
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Apoptosis
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Cell Line, Tumor
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Cell-Penetrating Peptides
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pharmacology
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Fluorescein-5-isothiocyanate
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analogs & derivatives
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Liposomes
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chemistry
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Melanoma, Experimental
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Mice
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Microscopy, Confocal
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Paclitaxel
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pharmacology
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Particle Size
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Polyethylene Glycols
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chemistry
2.Influence of Shenqifuzheng injection on efficacy of chemotherapy and immune function in patients with gas-tric cancer after surgery
Yufen XIE ; Ruiyang FU ; Xinjun GUAN
Chinese Journal of Primary Medicine and Pharmacy 2015;(20):3078-3081
Objective To explore the influence of Shenqifuzheng injection on efficacy of chemotherapy and immune function in patients with gastric cancer after surgery.Methods 60 postoperative patients with gastric cancer were selected as the research subjects,and were randomly divided into the control group and observation group by the digital table,30 cases in each group.The control group was given FOLFOX regimen chemotherapy.The observation group received FOLFOX regimen combined with the treatment of Shenqifuzheng injection.The recurrence and metasta-sis,survival,immune function and adverse reactions of the patients were observed and the patients were observed before and after chemotherapy.Results The chemotherapy cycle of the observation group was (3.95 ±0.40),which was significantly higher than (3.40 ±0.30)of the control group,the difference was statistically significant (t =6.025,P <0.01).The progression free survival in the observation group was (9 ±2.4)months,which was significant-ly longer than (6.6 ±3.2)months in the control group,the difference was statistically significant (t =3.286,P <0.01).The reduction rate in the observation group was 6.67%,which was lower than 26.67% in the control group, the difference was statistically significant (χ2 =4.320,P <0.05).The incidence rate of nausea and vomiting in the observation group was 6.67%,which was lower than 26.67% in the control group,the difference was statistically sig-nificant (χ2 =4.320,P <0.05).KPS[(83.51 ±15.37)points]and QLQ -C30[(82.01 ±9.45)points]of the observation group were significantly higher than those in the control group [KPS (74.62 ±13.22)points and QLQ -C30 (74.62 ±13.22)points],the differences were statistically significant (t =2.298,2.491,all P <0.05).After chemotherapy,gastric cancer patients ratio of CD +3 ,CD +4 ,CD +4 /CD +8 in the observation group were higher than those of the control group and the ratio of CD +4 /CD +25 in the observation group was lower than control group,the differences were statistically significant (all P <0.05).Conclusion Shenqifuzheng injection combined with FOLFOX chemo-therapy for gastric cancer patients has low adverse reaction rate,and can effectively improve the immune function.
3.Study on Inhabition Effect of Chitlsan Oligosaccharide on Tumour
Jie GUAN ; Dianjun LI ; Zhenkun FU
Journal of Medical Research 2006;0(01):-
Objective To observe the inhibition effect of chitlsan oligosaccharide on tumour. Methods The growth of tumour were observed after chitlsan oligosaccharide was injected into abdominal cavity(ip) or introtumour of mice;And the anti proliferation activities of chitlsan oligosaccharide on cells were evaluated by means of MTT assay. Results Growth of tumour were inhibited by chitlsan oligosaccharide, necrosis was observed in the tumour tissue.Chitlsan oligosaccharide affected the growth of cell. The effect was related to concentration of chitlsan oligosaccharide,but not depending of culture time.The apoptosis of cells could be seen under the transmission electron.Conclusion Chitlsan oligosaccharide could inhibit the growth of tumour and might induce apoptosis of cell.
4.Determination of Tanshinone Ⅱ_A in Huganning Tablets by HPLC
Xiaoliu FU ; Lei GUAN ; Demin ZHANG
China Pharmacy 2007;0(30):-
OBJECTIVE:To establish an HPLC method for the determination of Tanshinone Ⅱ A in Huganning tablets.METHODS:The determination was performed by HPLC using C18 column(200 mm?4.6 mm,5 ?m) with the column temperature maintained at 25 ℃.The mobile phase consisted of methanol-water(80∶20) at a flow rate of 1.0 mL?min-1 and a UV detection wavelength of 270 nm.RESULTS: The calibration curve of Tanshinone Ⅱ A was in good linearity over the range of 4.999~44.999 ?g?mL-1(r=0.999 7) and the mean recovery was 99.07%(RSD=0.33%,n=9).CONCLUSION: The method is sensitive,accurate and reproducible,and it can be used for the quality control of Huganning tablets.
5.Problems and countermeasures concerning medical personnel education in China
Li FU ; Fuhua XIAN ; Zhongjun GUAN ; Zhaofeng LV
Chinese Journal of Medical Education Research 2011;10(1):78-80
Human resources development in medical and health is of vital importance to medical and health sector reform and development as well as to medical and health existence and service improvement.Medical and health sector in China has made remarkable progress;however,facing the new requirements from economic and social development and people's new needs for medical health service because of their upaating health concepts and the new promotion by the development of biomedical science and technology,we still have some critical problems in medical and health personnel education.Therefore,the task of conducting careful analysis and exploring the solutions to these problems should be given sufficient attention and completed as soon as possible in the field of medical education.
6.Bioequivalence of Metoprolol Tartrate Tablets in healthy volunteers
Jing WANG ; Liangqing FU ; Yongbiao GUAN ; Yi FANG ; Zeyuan LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2004;0(09):-
AIM: To study the bioequivalence of domestic and imported Metoprolol Tartrate Tablets in Chinese healthy volunteers.METHODS: According to the rule published by SFDA,the serum concentration of 20 selected volunteers among 18 to 40 years old was determined by HPLC-fluorescence detection after giving domestic and imported Metoprolol Tartrate Tablets 0.1g,and the pharmacokinetic parameters were calculated by DAS software.RESULTS: The method of HPLC-fluorescence detection to study the pharmakokinetics of Metoprolol Tartrate was sensitive,reliable,accurate and reasonable.The main pharmakokinetics parameters of domestic and imported Metoprolol Tartrate Tablets were T_(max):(1.11)?(0.36 h) and(1.39)?(0.65 h) respectively;C_(max):(269.20)?(87.15)(?g?L~(-1)) and(262.03)?(75.52)(?g?L~(-1)) respectively;AUC_(0-12h):(1088.91)?(510.52)(?g?L~(-1)?h) and(1098.29)?5(55.14)(?g?L~(-1)?h) respectively.The relative bioavailability of domestic Metoprolol Tartrate Tablets was(100.09)%.CONCLUSION: The domestic and imported Metoprolol Tartrate Tablets was bioequivalents.
7.Retinervus luffae fructus protects against the myocardial ischemic injury in mice
Ying GUAN ; Jing LI ; Weijie ZHU ; Ling SUN ; Yongmei FU
Chinese Journal of Pathophysiology 1986;0(01):-
AIM: To observe the effect of Retinervus luffae fructus (RLF) on the myocardial ischemia in mice. METHODS: Mice were supplied with RLF (166.7,333.3, 666.7 g/L) twice daily (0.01 mL/g, ig). One week later, 30 U/kg pituitrin was injected intraperitoneally. The electrocardiogram was recorded, and the content of lactose dehydrogenase (LDH) in the serum and the activities of superoxide dismutase (SOD), maleicdialdehyde (MDA) in the myocardium were examined. RESULTS: RLF reduced the height of T wave in electrocardigram in myocardial ischemia mice and inhibited the decrease in heart rate. RLF also reduced the content of LDH in serum and the content of MDA in myocardium. The increase in the activity of SOD in myocardium was also observed. CONCLUSION: RLF may protect myocardium against ischemia injury. The mechanism may be related to the increase in activity of SOD and the suppression of the lipid peroxidation.
8.Exploration on the construction of severity of illness scoring systems in children with complex congenital heart disease after heart surgery
Tingting ZHANG ; Zhouying ZHUANG ; Yongmei GUAN ; Lijuan FU
Chinese Journal of Practical Nursing 2016;32(2):86-90
Objective The study aimed to construct one severity of illness scoring system specially for children with complex congenital heart diseases and analyzed the applicability of this new score,which will be helpful to assist the medical workers in evaluating children's condition.Methods A total of 1284children patients with complex congenital heart diseases in Shanghai Children's Medical Center Affiliated to School of Medicine of Shanghai Jiaotong University.The general information and clinical data were collected.Logistic regression,method of percentiles and expert opinions were used to construct the new severity of illness scoring system.Area under ROC curve,Hosmer-Lemeshow,goodness of fit test were used to evaluate the performance and applicability of the new score.Results A total of 1284 children with complex congenital heart diseases split into construction group (1138 cases) and verification group (146 cases).The new score included seven indexes (systolic blood pressure,blood oxygen saturation,lactic acid,potassium,potential of hydrogen,glucose,positive inotropic drug score).The range of the score was 0-57 and the cut-off point was 10.The discriminatory power was sufficient (area under the curve > 0.75),and the calibration capability of the score was tolerable (P > 0.05).Conclusions The applicability of the new score is well and it is easy to use,which will not increase the workload for the medical workers while assisting them in the clinical environment.
9.A study on correlations between Doppler velocity waveform parameters of fetal main pulmonary artery and gestation age in normal fetus
Yong, GUAN ; Shengli, LI ; Qian, FU ; Xinzhi, TU ; Guoyang, LUO
Chinese Journal of Medical Ultrasound (Electronic Edition) 2014;(1):38-43
Objective To explore the correlations between measurements of Doppler velocity waveform parameters of fetal main pulmonary artery and gestation age (GA) in normal fetus. Methods This is a cross-sectional study, in which totally 252 normal singleton fetuses between 23 and 40 weeks of gestation were divided into 10 groups. The following velocity waveform parameters were measured in the main trunk of fetal pulmonary artery by Doppler ultrasound: acceleration time(AT), ejection time(ET), acceleration time/ejection time(AT/ET), peak systolic velocity(PSV), end diastolic velocity(EDV), mean velocity(MV), pulsatility index(PI) and resistance index(RI). The normal reference values of Doppler velocity waveform parameters at various GA were established. A scatter diagram of each parameter against GA was plotted out. The optimal formula was selected out according to the correlation and regression analysis. Results Among 252 normal fetuses, satisfactory Doppler velocity waveform of fetal main pulmonary were achieved in 249 (98.8%, 249/252). Among these parameters, AT, AT/ET, PSV, EDV and MV increased with increasing GA(F=343.23, 96.012, 8.649, 2.158, 10.169, all P<0.05), while PI decreased slightly(F=2.346, P<0.05) and ET, RI had no signiifcant changing(F=0.883, 1.534, both P>0.05). Signiifcant and positive linear correlations were found between parameters of AT, AT/ET, PSV, EDV, MV and GA(r= 0.898, 0.868, 0.446, 0.203, 0.507, all P<0.01);while PI was inversely linear correlated with GA(r=-0.184, P<0.01) and ET, RI had no correlation with GA(r=-0.103, 0.011, both P>0.05). Conclusions The fetal main pulmonary artery could be a reliable sampling point to obtain pulmonary velocity waveform by Doppler ultrasound. Doppler velocity waveform parameters have correlations with GA in normal fetus;among which AT and AT/ET were the best.
10.Methotrexate for hip involvement of ankylosing spondylitis:a clinical study
Fu-Tao ZHAO ; Jian-Long GUAN ; Xing-Hai HAN ;
Chinese Journal of Rheumatology 2001;0(04):-
Objective To evaluate the efficacy and safety of methotrexate(MTX)on the hip involve ment in patients with ankylosing spondylitis(AS).Methods Among the AS patients with hip joint involvement admitted to the department from 1999—2002,50 patients were treated with sulfasalazine(SSZ)(control group, CG)and 48 MTX(observation group,OG).One kind of NSAIDs was taken by the patients in both groups as the basic therapy.The treatment was maintained in both groups after being discharged.Patients were followed-up for three years.The observation parameters included symptoms,signs,Bath AS disease activity index(BASDAI), Bath AS functional index(BASFI),hip joint function score,the CT staging of hip joint involvement,serum in- flammation markers,laboratory tests and side effects.The data were analyzed with SPSS10.0 statistics software. Results At the 1st,2nd and 3rd year,44,38 and 32 cases in the OG and 45,38 and 31 cases in the CG were followed up respectively.During the three-year follow-up period,the hip joint function score of the OG was significantly higher than that of the CG(P