Child ; Drugs, Chinese Herbal ; toxicity ; Ganglion Cysts ; pathology ; Humans ; Leigh Disease ; chemically induced ; diagnostic imaging ; Male ; Medicine, Chinese Traditional ; adverse effects ; Plant Roots ; chemistry ; Radionuclide Imaging ; Sophora ; toxicity ; Tomography, X-Ray Computed

AIM:To investigate the relationship between autophagy and calcification in vascular smooth muscle cells ( VSMCs) after platelet-derived growth factor (PDGF)-BB stimulation.METHODS:Cultured VSMCs were stimulated with PDGF-BB for different time, the expression of vascular calcification-related proteins and autophagy-related proteins were detected by Western blot .The interaction be-tween Beclin1 and PI3KC3 was detected by co-immunoprecipitation.RESULTS: The expression of BMP2 and ALP showed a trend from decline to rise.ALP slumped at 12 h, and BMP2 slumped at 6 h.Moreover, the expression of Beclin-1 showed a trend from rise
to decline, and peaked at 12 h.The conversion of LC3-ⅠtoⅡincreased in a time-dependent manner , and peaked at 24 h.The ex-pression of BMP2 and ALP was increased in VSMCs incubated with PDGF-BB and autophagy inhibitor 3-MA, compared with PDGF-BB-stimulated VSMCs.Furthermore, the interaction between Beclin1 and PI3KC3 was enhanced at 6 h after PDGF-BB stimulated, peaked at 12 h, and kept in high level at 24 h.Moreover, the phosphorylation level of Beclin 1 was enhanced by PDGF-BB stimulation, and peaked at 6 h.CONCLUSION:Our findings demonstrate that PDGF-BB-induced autophagy inhibits VSMC calcification by en-hancing Beclin1 phosphorylation and interaction between Beclin 1 and PI3KC3.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Ferritins ; blood ; Hemoglobins ; metabolism ; Humans ; Killer Cells, Natural ; L-Lactate Dehydrogenase ; blood ; Lymphoma, T-Cell ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Nose Neoplasms ; blood ; drug therapy ; pathology ; Prognosis

Objective To explore the mechanism of endotoxemic injury in kidneys and protective effect of dexamethasone on renal cells.Methods Fifty-four eighteen-day Wistar rats were divided into control,endotoxemic(LPS)and dexamethasone groups randomly,18 rats in every group.Rats in control group were injected intraperitoneally with the same volume(0.1 mL)of 9 g/L sodium chloride as other two groups.All rats in LPS group were injected with a single bolus of LPS(4 mg/kg).The rats in dexamethasone group received LPS(4 mg/kg)and dexamethasone(5 mg/kg).Then they were sacrificed at 6,24 and 72 hours after injection.The ultrastructure was observed by electron microscope.Results In LPS group,glomerular basement membrane became thick and foot processes had coalescent partly,mitochondrial cristae became dissolved in proximal tubular endothelial cells and microvillus of distal tubular diminished at 6,24 hours after LPS injection.The morphological changes of apoptosis were found in the proximal tubular at 72 hours after LPS injection.These changes were in dexamethasone group.Conclusion Apoptosis participates in LPS injury of kidneys and dexamethasone have protective effect on injuried renal cells.

Carrier State ; virology ; Female ; Hepatitis B ; complications ; Humans ; Lymphoma, Large B-Cell, Diffuse ; virology ; Male ; Middle Aged

Objective To evaluate the effects of different concentrations of parecoxib sodium on the rat sperm motility,capacitation and acrosome reaction in vitro.Methods The sperm samples from Sprague-Dawley rat epididymis were collected by Klinefelter diffusion method and randomly divided into 4 groups (n =18 each) using a random number table:control group (group C),and parecoxib sodium 100,500,1 000 μmol/L groups (P1-3 groups).Parecoxib sodium with the final concentrations of 100,500 and 1 000 μmol/L was added to the culture medium.The samples were then incubated for 5 h in an airtight container filled with 5 ％ CO2 at 37 ℃.Then sperm motility was examined in vitro at 37 ℃ and analyzed by the computer-assisted sperm analysis,including the sperm motility ((a + b)％),average path velocity (VAP),straight line velocity (VSL),curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH).The capacitation effect was assessed by using the chlortetracycline staining and phase-contract microscopy.The acrosome reaction was evaluated by coomassie brilliant blue staining.Results The VAP,VSL,VCL and capacitation ability of the sperm were gradually decreased in C and P1-3 groups (P ＜ 0.05).Compared with group C,(a + b)％ in P2,3 groups and ALH in P2 group were significantly decreased (P ＜ 0.05).There was no significant difference in the acrosome reaction between groups (P ＞ 0.05).Conclusion Parecoxib sodium has significant inhibitory effects on the rat sperm motility and capacitation in a dose-dependent manner,while has no effect on the acrosome reaction in vitro.

Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.
Algorithms ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Humans ; Intestinal Absorption ; Intestines ; chemistry ; metabolism ; Models, Theoretical ; Solubility

Objective To explore the influence of low-selenium diet on expression of selenium-binding protein 1 (SBP1) and selenoprotein P (Sel P) in liver,kidney and brain tissues.Methods C57BL/6 mice were randomly divided into four groups according to body weight:control group,low-selenium treatment for 4-,12-and 24-week groups,10 mice in each group,half male and half female.The control group was fed with normal diet (selenium content was 0.300 mg/kg),distilled water,and sacrificed at the 12th week; low-selenium treatment groups were fed with low-selenium diet(selenium content was 0.015 mg/kg),then sacrificed at the 4th,12th and 24th weeks,respectively.Expressions of SBP1 and Sel P in mouse liver,kidney and brain tissues were determined by Western blotting.Results Expressions of SBP1 and Sel P in low-selenium feed mouse liver tissue at the 4th,12th and 24th weeks were,respectively,as follows 0.11 ± 0.01,0.36 ± 0.01,0.59 ± 0.02 and 0.41 ± 0.01,0.39 ± 0.02,0.25 ± 0.02;in kidney,respectively,as follows 0.60 ± 0.03,0.20 ± 0.02,0.03 ± 0.01 and 0.88 ± 0.01,0.73 ± 0.03,0.85 ± 0.02; in brain,respectively,as follows 0.54 ± 0.03,0.11 ± 0.01,0.01 ± 0.01 and 0.50 ± 0.02,0.49 ± 0.03,0.38 ± 0.02.Expression of Sel P in low-selenium feed mouse liver,kidney and brain tissues was significantly decreased as compared to that of control group(1.00 ± 0.00,1.00 ± 0.00,all P ＜ 0.05),but SBP1 content was reduced at first and then rebounded in kidney,and was in decreasing trend in liver and brain tissues.Conclusion Low-selenium diet has a certain effect on expression of SBP1 and Sel P in mouse liver,kidney and brain tissues.

The method of homogeneity evaluation for active pharmaceutical ingredient (API) spatial distribution in lyophilized product was investigated for the first time with confocal micro-Raman spectroscopy mapping, using pemetrexed disodium for injection as a model drug. Certain areas of the lyophilized product were scanned to obtain Raman spectra. The classical method ("peak clipping" method) was employed for mapping with characteristic Raman peaks of the API and the excipient. Due to the API being finely dispersed in the excipient in lyophilized products, the classical method cannot discriminate between the two ingredients making the distribution homogeneity difficult to evaluate. The "ratio of characteristic peak intensities" method was then utilized. Using this method, the relative intensity of the characteristic Raman peaks of the API to the excipient was applied for mapping and the relative content of API to excipient was calculated for a homogeneity evaluation of the drug distribution. The validation of this method showed a good linear relationship between the relative intensity and the relative content of API to excipient (r² > 0.99), and the precision and recovery were adequate for homogeneity evaluation of API by Raman spectroscopy mapping. Five products of pemetrexed disodium for injection from different manufacturers were tested through Raman maps applying this method and the histograms of relative Raman intensity were also plotted by frequency to help the homogeneity evaluation of drug distribution. The results showed that there were obvious differences in the drug distribution homogeneity from different products, where a more homogeneous API distribution was found in the brand product. This research provides a reliable method for the homogeneity evaluation of API distribution, which facilitates quality evaluation and process optimization of lyophilized products.

OBJECTIVETo assess the efficacy and safety of recombinant human thrombopoietin (rhTPO) on chemotherapy-induced thrombocytopenia in patients with solid tumor.

METHODSIn this randomized crossover self-controlled multi-center clinical trial, 154 patients with solid tumor were randomly divided into two groups (group A 77 cases and group B 77 cases). All patients were given the same two cycles of chemotherapy. In group A, the first cycle was treated cycle, in which patients were given rhTPO, while the second cycle was non-treated cycle as a control. In group B, the first cycle was non-treated cycle as a control, while the second cycle was treated cycle. RhTPO 1.0 microg/(kg x d) was administered subcutaneously 6-24 hours after chemotherapy for the longest 14 days. Laboratory tests included complete blood counts, urinalysis, serum chemistry, coagulant test, chest radiography, and electrocardiogram. Serum samples were screened for anti-rhTPO antibodies.

RESULTSIn both group A and group B, platelet decrease and duration had no significant difference between the treated cycle and non-treated cycle. Platelet count was higher in the treated cycle, than in the non-treated cycle: [minimal mean platelet count (64.4 +/- 45.4) x 10(9) cells/L and (52.4 +/- 30.9) x 10(9) cells/L (P=0.000), maximal mean platelet count (263.9 +/- 142.5) x 10(9) cells/L and (148.9 +/- 67.7) x 10(9) cells/L (P=0.000)]. Duration of thrombocytopenia was shorter in the treated cycle than in the non-treated cycle [days with platelet count < 50 x 10(9) cells/L, (2.5 +/- 3.9) and (3.7 +/- 5.7) (P=0.04); days with platelet count recovered > or = 75 x 10(9) cells/L, (10.3 +/- 8.7) and (14.0 +/- 8.9) (P=0.000), and days with platelet count recovered > or = 100 x 10(9) cells/L, (15.9 +/- 10.5) and (21.1 +/- 9.5) (P=0.000)]. The need for platelet transfusion was not significantly reduced in treated cycle. The effects of rhTPO on WBC, Hb, hepatic function, renal function, and coagulant function were not found. Transient low-titer non-neutralizing antibody was developed in one patient. Therapy with rhTPO was tolerated by all patients. Mild side effects were observed in individual patients, including fever, dizziness, and chill. Conclusion Administration of rhTPO after chemotherapy can significantly reduce the degree and duration of thrombocytopenia and promote platelet recovery. Therapy with rhTPO seems to be safe.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Cross-Over Studies ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Neoplasms ; blood ; drug therapy ; Platelet Count ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; prevention & control ; Thrombopoietin ; therapeutic use