Objective To investigate the therapeutic effect of levosimendan on acute decompensated heart failure and its effect on SDNN and SDANN values.MethodsThe clinical data of patients with acute decompensated heart failure treated in Zhejiang Greentown Cardiovascular Hospital from January 2014 to August 2016 were retrospectively analyzed.According to their treatment methods, they were divided into control group and observation group.There were 49 cases in the control group and 71 cases in the observation group.The control group was given conventional drug treatment, the observation group was given levosimendan treatment on the basis of the control group.The therapeutic effects of the two groups were observed.The difference of cardiac function, SDNN, SDANN value and adverse reaction between the two groups were compared before and after treatment.ResultsAfter treatment, the observation group efficiency was 98.59%, significantly higher than the control group;the observation group LAD, RAD, LVESD, LVEDD and BNP lower than the control group, the level of LVEF was higher than the control group, the difference was statistically significant (P<0.05);the observation group SDNN, SDANN, RMSSD and PNN50 (%) was higher than that of the control group, the difference was statistically significant (P<0.05).ConclusionLevosimendan has good therapeutic effect on acute decompensated heart failure, can significantly improve the level of SDNN, SDANN, and the incidence of adverse reactions is low.

OBJECTIVE:To compare and analyze the ADR in Chinese Pharmacopoeia(2010 edition)(ChPD)and non-phar-macopoeia quality standard drugs(NChPD)and its standard. METHODS:In respective study,ADR reports and drug utilization da-ta in our hospital from 2012 to 2014 were collected and divided into ChPD group and NChPD group,the index differences were an-alyzed. RESULTS:The percentages of reported ADR to product regulation [(0.27 ± 0.10)%] and to drug use frequency [(0.15 ± 0.06)%] in ChPD group were significantly lower than NChPD group [(0.62 ± 0.08)%、(0.32 ± 0.07)%],with statistical signifi-cance (P<0.05). Compared with the percentage of general reported ADR to drug use frequency in NChPD group [(0.44 ± 0.12)%],there was no significant difference in ChPD group [(0.23±0.09)%](P>0.05);the percentage of new severe reported ADR to drug use frequency in ChPD group [(0.04 ± 0.01)%] was significantly lower than NChPD group [(0.27 ± 0.05)%],with statistical significance (P<0.05). And there were no significant differences in indexes in different years (P>0.05). CONCLU-SIONS:Drug quality standards should be payed more attention,from the perspective of which to reduce the incidence of adverse drug reactions. While the drugs introduced to hospital should be strictly controlled and timely adjust the drug structure;the pharma-copoeia standard drugs should be generalized among doctors to reduce ChPD drug reactions and ensure the drug safety.

Objective To investigate curative efficacy of ginkgo biloba extract dripping pills in treatment of acute coronary syndrome(ACS) after percutaneous coronary intervention(PCI) and its effects on platelet aggregation rate(PAR), activated clotting time(ACT) and antithrombin(AT)Ⅲ. Methods 90 patients of ACS treated with PCI who received therapy from January 2014 to October 2016 in Zhejiang green town cardiovascular hospital were selected and randomly divided into the observation group and the control group , 45 cases in each group.The control group was treated with routine treatment after PCI, while the observation group was combined with ginkgo biloba extract dripping pills.After treatment of seven days, the changed of PAR, ACT, ATⅢ and adverse cardiovascular events were compared, after treatment three months, the seattle angina scale were compared. Results After treatment, the levels of PAR in the observation group were significantly lower than that of the control group, and the levels of ACT and ATⅢ were significantly higher than that of the control group, the difference was statistically significant (P<0.05), the total incidence of adverse cardiovascular events in the observation group was significantly lower than that of the control group , the difference was statistically significant ( P<0.05), in the seattle angina scale, the scores of stable state of angina pectoris, the attack of angina pectoris, physical activity limitation, treatment satisfaction in the observation group were significantly better than that of the control group, the difference was statistically significant (P<0.05). Conclusion Ginkgo biloba extract dripping pill is well for ACS after PCI, which can effectively relieve clinical symptoms, to improve the expression of PAR, ACT and ATⅢ, helps to reduce the incidence of adverse cardiovascular events.

Objective To prepare the sinomenine hydrochloride multivesicular liposomes with high entrapment efficiency and sustained release character.Methods Multiple emulsion method was used to prepare the sinomenine hydrochloride multivesicular liposomes.Uniform design was applied to optimize the formulation and pharmaceutical process.The shape,the particle size,and the release charcter of the liposome were evaluated.Results The sinomenine hydrochloride multivesicular liposomes prepared were spherical and the size of majority particles was in the range of 20—30 ?m and well distributed.The encapsulation efficiency was more than 80% and its in-vitro release profile accorded well with the Higuchi model with t1/2 up to 52.7 h.Conclusion The formulation and pharmaceutical process of the sinomenine hydrochloride multivesicular liposomes are stable and feasible with the high encapsulation efficiency and good sustained-release character.

Objective:To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxici-ties related to high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis (DGGE), and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:We identified three SNPs of GSTP1, including rs1695 (A313G), rs1138272 (G439T), and rs4891 (T555C). The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases (62.7%), 16 cases (31.4%), and 3 cases (5.9%), respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin (OR=0.25, 95%CI=0.06-1.00, P=0.049). The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity (OR=0.125, 95%CI=0.02-0.78, P=0.026). Conclusion:GSTP1 rs1695 (A313G)/rs4891 (T555C) gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.

Objective To prepare a thrombus-targeted ultrasonic contrast agent and to investigate its targeted ability to fresh blood clots. Methods We first synthesized FITC-KGDS-Palm compound, and then prepared thrombus-targeted microbubbles using "ultrasound & high speed shearing method".Fluorescence labeling thrombus-specific peptides and KGDS,directed at the activated glycoprotein(GP)Ⅱb/Ⅲa receptor of platelets were attached to the surface of lipid microbubbles. The concentration and size of TUCA were measured by Malvern Zeta Sizer Nano-ZS590 and Coulter counter.Immunofluorescence was applied to confirm the conjugation.The conjunct ratio was assessed by flow cytometer (FCM).Results The KGDS-TUCA was straw yellow turbid liquor,and the concentration was 1.5×10~9/mL,and the average size was 1.5 μm. The targeted microbubbles conjugated with the thrombus-specific peptides showed bright green rings by fluorescence microscope.FCM demonstrated that the wavelength of shell of KGDS-TUCA changed greatly,and the conjunct ratio was 90.04%.In vitro study showed KGDS-TUCA remained stable for 48 h at 4 ℃ and target-attached to blood clots and showed good stability.Conclusion The ultrasound & high speed shearing method to prepare TUCA is easy and in favor of purification.KGDS-TUCA has high specific biological activity.The conjunct ratio and stability of KGDS-TUCA are excellent.

Objective:To investigate the correlation between polymorphisms of serine hydroxymethyltransferase1 gene and the adverse reactions of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:A total of 51 patients with ALL were treated with HD-MTX, and clinical manifestations after HD-MTX treatment were evaluated retrospectively. cD-NA was obtained from mRNA. The polymorphisms of SHMT1 gene containing rs1979277, rs3783, rs1979276, and rs12952556 sites were tested by denaturing gradient gel electrophoresis and direct sequencing. Effects of SHMT1 gene polymorphisms on HD-MTX ad-verse reactions were evaluated. Results:Severe adverse reactions in ALL patients treated with HD-MTX appeared to be mainly neutro-penia and hepatoadverse reactions. The frequency distributions of rs3783 (C>G), rs1979276 (C>T), rs12952556 (A>G), and rs1979277 (C>T) were the same. The polymorphisms of rs1979277 showed no correlation with neutropenia (P>0.05) but rs1979277 CT and TT genotypes were correlated with hepatoadverse reactions (CT: OR=0.129, 95% CI: 0.020 to 0.817, P=0.03; TT: OR=0.103, 95% CI:0.017 to 0.620, P=0.013). Conclusion: No correlation was found between the combination of rs1979277, rs3783, rs1979276, rs12952556, and neutropenia, but one or more of these loci may reduce the risk of hepatoadverse reactions.

Objective To prepare sinomenine hydrochloride transfersomes and evaluate their qualities. MethodsThree different preparation methods including film dispersion, reverse phase evaporation, and ethanol injection methods were compared according to the encapsulation efficiency of transfersomes. Uniform design was applied to optimize the formulation and pharmaceutical process of reverse phase evaporation. The particle size, the appearance, the Z-potential, and the stability were also evaluated. ResultsThe transfersomes prepared by reverse-phase evaporation method possessed the highest encapsulation efficiency. The ideal combinations of preparation and formulation were: soya lecithin/sodium cholate was 200/30 mg/mg, chloroform/PBS was 5 mL/mL, pH of PBS was 6.5, added sinomenine hydrochloride was 10 mg. The transfersomes obtained were milky white translucent suspension, with a mean encapsulation efficiency of 62.2%. The shape of their particles was spherical or similar to spherical under microscope, which was smooth and disconglutinated with an average diameter of 96.4 nm, and a Z-potential of-35.93 mV. Aggregation or deposition was not observed after exposure under the temperature of 4 ℃ for 30 d. ConclusionThe preparation process of sinomenine hydrochloride transfersomes is feasible, the quality of obtained transfersomes is stable.It is expected to provide a new preparation for clinical use of sinomenine hydrochloride.

Objective To explore the semitivity of ovarian cancer cell line SKOV3 to paclitaxel,oroteasome inhibitors,bortezomib,and their combination.Methods The methyl thiazolyl tetrazolitim (MTT)assay was applied to examine the cell viability after treatment.The annexin V-propidium iodide apoptosis detection kit was used to determine the apoptosis rate of different groups.Western blot assay was used to evaluate the expression levels of phosphorylated protein kinase B(AKT)and glycogen synthase kinase-3 beta(GSK-3β).Results In MTT assay,the cell viability ratios of the combination group at serial time points from 12,24,36,48 and 72 hours Were(65.2±5.8)%,(58.3±14.4)%,(35.3±5.0)%,(19.2±1.5)%,and(11.4 ±2.5)%,which were significantly lower than those of the paclitaxel group (P<0.05).After arug treatments,apoptosis rates of paclitaxel group,bortezomib group and the combination group were (14.7±0.5)%,(15.1±0.8)%and(20.5±0.7)%respectively.The rate of the combination group was significantly higher than that of non-treated group and paclitaxel group(P<0.05).Western blot assay showed the changes in expression levels of phosphorylated AKT and GSK-3β,which were decreased significantly after paclitaxd and bortezomib combination treatment [(3.2±0.8)%,(19.3±0.4)%;P<0.05].Conclusions The lethal effect of paclitaxel on tumor cells could be increased significantly by its combination with proteasome inhibitors,bertezomib.The AKT/GSK-3β signaling pathway plays an important role in the molecular mechanism of the combination treatment.

OBJECTIVETo isolate a subclone from human colorectal cancer cell line SW480 with unique metastatic potential in the liver.

METHODSHuman colorectal cancer cells SW480 were implanted into BALB/c nude mice, and the hepatic metastatic lesions were harvested, and the tumor tissue blocks were re-implantated into nude mice for a second round of in vivo selection. The same procedure was repeated 5 times until a new cell subline, designated as SW480/M5, was established, whose biological behaviors was investigated both in vivo and in vitro.

RESULTSAfter orthotopic implantation of the tumor tissue into the colon of nude mouse for 28 days, widespread loco-regional and distant metastases occurred in mice inoculated with SW480 tissue, and those inoculated with SW480/M5 tissue had hepatic metastasis only. Compared with the parental cells, SW480/M5 cells were characterized by greater clonality, reproductive activity, motor ability, invasiveness, and weaker adhesive capacity to fibronectin.

CONCLUSIONA human colorectal cancer cell subline with unique liver metastatic potential has been established by in vivo selection to serve as a new model for study ing colorectal cancer metastasis.

Animals ; Colorectal Neoplasms ; pathology ; Female ; Humans ; Liver Neoplasms, Experimental ; secondary ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Transplantation, Heterologous ; Tumor Cells, Cultured