Objective To investigate the genotoxicity of heavy rare-earth holmium to bone-marrow cells of mice.Methods Kunming mice were randomly divided into six groups and were given holmium-trioxide-HCl by gavage at several doses of 0,10,20,40,80 and 160 mg/kg bw respectively one time a day for two days;other Kunming mice were randomly divided into 3 groups and holmium nitrate was given i.p.at doses of 10,40 and 80 mg/kg bw respectively one time a day for two days.24 hours after the last treatment,the bone-marrow cells of thighbone were collected for micronuclei analysis and single cell gel electrophoresis (SCGE).Results Frequencies of micronuclei were increased by the 2 kinds of holmium solutions at the dosage from 10 to 80 mg/kg bw with a dose-effect relationship,but at the dose of 160 mg/kg bw,it was lower than the negative control.In SCGE,the average tail length increased significantly (P

This study is to prepare the pantoprazole sodium enteric-coated tablet which is compacted by pellets. The enteric-coated pantoprazole sodium pellets were prepared by fluid bed coating technology. The pantoprazole sodium enteric-coated tablets were prepared by direct compression of the enteric-coated pellets and suitable excipients. In vitro dissolution method and scanning electron microscope method were used for the observation of the drug release behavior before and after compression of the pellets. The optimized formulation is: the coating level is 55%, the plasticizer content is 20%, the ratio of Eudragit L30D-55/NE30D is 8 : 2, enteric-coated pellets/excipients (MCC/PPVP/PEG 6000 = 2 : 1 : 1) is 5 : 5, the enteric-coated tablets release in artificial gastric fluid in 2 h is less than 10%, while in artificial intestinal fluid in 1 h is more than 85%. The release behavior of pantoprazole sodium enteric-coated pellets-type tablet is quite well. And it may be used in industrial production.

Pluronic modified polyamidoamine (PAMAM) conjugate (PF127-PAMAM) was prepared and the inhibiting effect of MDR against MCF-7/ADR was investigated with doxorubicin (DOX) as model drug. 1H NMR and FTIR spectra showed that the conjugate was synthesized successfully. Element analysis accurately measured that 27.63% amino of per PAMAM was modified by pluronic (PAMAM : PF127, 1 : 35.37 mole ratio). PF127-PAMAM showed an increased size and a reduced zeta potential compared to PAMAM. PF127-PAMAM had lower hemolytic toxicity and cytotoxicity due to the reduced zeta potential and the protection of PF127. Each PF127-PAMAM molecular could load 19.58 DOX molecules, and the complex exhibited sustained and pH-sensitive release behavior. PF127-PAMAM/DOX exhibited weaker cytotoxicity than free DOX in MCF-7 cells; while the complex showed much stronger reverse effect of drug resistance in MCF-7/ADR cells, and resistance reversion index (RRI) was as high as 33.15.

The study is to prepare taste masking and enteric-coated clarithromycin granules by melting and fluid bed coating technology. Clarithromycin and matrix materials were melted at a certain temperature, and then made into particles by fluidized bed coating. X-ray powder diffraction and scanning electron microscopy were used to identify the crystal and morphology of drug loading granules. In vitro dissolution method was used for the observation of the drug release behavior. The results showed that the drug particles size range was 0.2 - 0.6 mm; the crystal form of clarithromycin in the granule did not change; enteric-coated granules accumulated release in 0.1 mol L(-1) hydrochloric acid in 2 h was less than 10%, while in pH 6.8 phosphate buffer in 1 h was more than 80%. The taste masking and enteric-coated clarithromycin granules not only have good taste masking effect, but also have a good release behavior. It is expected to have better clinical application.

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.

Background and purpose:Neoadjuvant chemotherapy with docetaxel was gaining more attention in the treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). The prediction of the sensitivity to neoadjuvant chemotherapy with docetaxel could enable clinicians to individualize treatment protocols for NPC. Recently we found that 99mTc-MIBI imaging in NPC could predict tumor response to chemotherapy with cisplatin plus 5-FU. However, there was no study to support similar findings in NPC patients receiving chemotherapy containing docetaxel. This study was to evaluate the value of double-phase 99mTc-MIBI SPECT/CT in predicting response to neoadjuvant chemotherapy with docetaxel-based regimen for nasopharyngeal carcinoma. Methods:Thirty-one nasopharyngeal carcinoma patients participated in this prospective study. Before treatment, early and delayed single-photon emission computed tomography/compute tomography (SPECT/CT) images were obtained instantly and 2 hours after an intravenous injection of 25-30 mCi 99mTc-MIBI. All patients received neoadjuvant chemotherapy consisting of docetaxel, cisplatin plus 5-FU for two cycles. The relationships between efficacy of neoadjuvant chemotherapy and the early uptake ratio, late uptake ratio and washout rate of 99mTc-MIBI were evaluated.Results:According to the MRI, the early uptake of 99mTc-MIBI (2.67±0.83) in the lesions which were sensitive to chemotherapy was significantly higher compared with that (1.69±0.46) in the insensitive lesions(P=0.003). The difference of the late uptake between the sensitive(1.46±0.39) and the insensitive (1.06±0.62) was also statistically significant (P=0.026). However, the washout rate of 99mTc-MIBI was not significantly different between the two groups (P=0.23). Through ROC curve analysis, the AUC for early uptake of 99mTc-MIBI and late uptake were 0.84. The sensitivity, specificity, positive predictive value and negative predictive value were 74.2%, 87.5%, 95.8%and 46.7%for early uptake when the cut off value of 1.97 was used. Conclusion:The uptake of 99mTc-MIBI in both early phase and late phase could predict the efficacy of neoadjuvant chemotherapy with docetaxel-based regimen.

Objective:To explore the optimal labeling conditions of 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)- D-Phe1-Tyr3-Thr8-octreotide (TATE), and evaluate its biodistribution and imaging characteristics in mice. Methods:The reaction temperature, pH, reaction time and other labeling conditions were changed to realize the rapid labeling of NOTATATE by 177Lu. The optimal labeling conditions, radiochemical purity, in vitro stability, plasma protein binding rate, and lipid-water partition coefficient were determined. Twenty-four normal KM mice were divided into 6 groups by random number table method. After injected with 3.7 MBq 177Lu-NOTATATE through tail vein, they were sacrificed at 0.5, 1, 4, 24 h and 4, 6 d respectively to research the biological distribution (injection dose rate per gram of tissue percentage, %ID/g). Six normal mice were randomly divided into 2 groups and injected with 11.1 MBq 177Lu-NOTATATE and 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)TATE, respectively. SPECT planar imaging was performed at 1, 2, 3 h after injection. Another 8 mice were divided into 4 groups, injected with 3.7, 7.4, 18.5 MBq 177Lu-NOTATATE and saline respectively for an acute toxicity test. Results:At pH 5 and reaction temperature between 95 ℃ and 100 ℃ for 15 min, the labeling rate could reach more than 98%. After being placed in human serum for 24 h, the radiochemical purity was still higher than 95%. The plasma protein binding rate of 177Lu-NOTATATE was (58.6±1.9)% and the lipid-water partition coefficient was 0.048±0.014. In normal mice, the concentration of radioactivity is mainly in the liver, kidney and spleen, especially in the kidney (up to (29.120±1.204) %ID/g after 0.5 h of injection), which is less distributed in the blood and excreted rapidly. Compared with 177Lu-DOTATATE, 177Lu-NOTATATE was excreted faster by the kidney. The toxicity study results revealed that no damage was observed in mice of each group, and no obvious damage or inflammatory changes were observed in organ tissue sections. Conclusions:The optimal labeling condition of 177Lu-NOTATATE were determined in this study. The physical, chemical, and biological properties of 177Lu-NOTATATE were proved to be good and safe, and it was excreted faster by the kidney than 177Lu-DOTATATE. The results of this study lay a foundation for further clinical transformation research.

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.