OBJECTIVE: To develop phospholipid vehicle to improve the bioavailability of curcumin after oral administration. METHODS: Two phospholipid vehicles, including phospholipid complex and liposome, were prepared. The characteristics, such as entrapment efficiency, shape, size, and structure, were compared. An in situ recirculation method was used to investigate the intestinal absorption of both phospholipid vehicles. RESULTS: Spherical or elliptical vesicles were observed under transmission electron microscope and atomic force microscope after the phospholipid vehicles were dispersed in water. The average entrapment efficiencies of phospholipid complex and liposome were (90.81 ± 1.32)% and (81.59 ± 2.41)% respectively. The mean sizes and zeta electric potentials were (91.69 ± 12.26) nm and (-13.73 ± 4.37) for the phospholipid complex, and (76.39 ± 8.58) nm and (-11.27 ± 1.26) for the liposomes. DSC, IR and Raman spectrum verified that there was reaction between curcumin and the phospholipid polar group around phosphorus atom in the complex but not in the liposomes. The apparent permeability coefficients (Papp) in the whole intestine were (1.1312 ± 0.0498) and (0.4780 ± 0.0120) 10 -6 cm-2 · s-1 for the complex and liposome respectively, which were 17.60 times and 5. 90 times higher than the crude drug. The absorption rate constants (Ka) and Papp of the complex were higher than the liposomes at duodenum, colon and ileum significantly. There was no difference at jejunum. CONCLUSION: Phospholipid complex can promote the absorption of curcumin in a larger degree than liposomes.

OBJECTIVETo observe microvessel density(MVD), epithelial stromal vascular cuffing(VC) and expression of vascular endothelial growth factor(VEGF) in human cervical carcinomas and to clarify their significance in the invasion and metastasis of cervical carcinoma.

METHODSVEGF and CD34 were stained immunohistochemically (SP) in 57 cases of cervical carcinoma (30 cases of squamous cell carcinoma, 20 of adenocarcinoma 7 of glandular and squamous cell carcinoma), 29 cases of cervical intraepithelial neoplasia (CIN) and 16 cases of normal cervices, meanwhile, MVD and VC were also assayed.

RESULTSThere were significant differences among the above 5 groups for MVD P<0.01 . The VC pattern showed a significant difference between cervical carcinoma and CIN or control group P<0.01). The positive rates of VEGF in normal cervical epithelium, CIN, squamous cell carcinoma, adenocarcinoma, glandular and squamous cell carcinoma were 18.8% 3/16, 82.8% 24/29), 93.3% 28/30), 100% 20/20 and 7/7(100%), respectively. There were significant differences between these cervical lesion groups and the control group(P<0.001). The MVD showed significant differences between the positive pelvic node metastasis and negative pelvic node metastasis P<0.05). There was no significant correlation between the expression of VEGF and the tumor diameter, clinical stage, pathologic grade and pelvic node metastasis.

CONCLUSIONThe expression of VEGF may play an important role in the angiogenesis of cervical carcinoma. Degree of malignancy of cervical carcinoma has a close association with microvessel density.

Adult ; Aged ; Aged, 80 and over ; Endothelial Growth Factors ; analysis ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; Lymphatic Metastasis ; Lymphokines ; analysis ; Microcirculation ; Middle Aged ; Uterine Cervical Neoplasms ; blood supply ; chemistry ; pathology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Objective To comprehensively analyze the nursing measures of early thrombolytic therapy for acute myocardial infarction. Methods 140 patients with acute myocardial infarction admitted in our hospital from October 2013 to October 2016 were randomly divided into control group (70 cases) and experimental group (apply early thrombolytic care on the basis of routine nursing method, 70 cases) according to different nursing methods. SPSS20.0 statistical software was used to analyze the incidence of complications, mean hospitalization time, average bedridden time and total satisfaction. Results The average hospital stay and the average length of stay in the experimental group were much shorter than those in the control group (P<0.05). The total score of the experimental group was much higher than that of the control group (P<0.05). The complication rate of the experimental group was much lower than that of the control group (P<0.05). Conclusion Nursing measures for early thrombolytic therapy in patients with acute myocardial infarction can significantly reduce the incidence of complications in patients.

OBJECTIVETo evaluate the antiproliferative activity of 3-(2-chlorophenyl)-1-(2-hydroxy-4, 6-dimethoxy-3-((ethyl(methyl) amino) methyl) phenyl) prop-2-en-1-one (DMF) against human androgen-independent prostate cancer PC3 cells in vitro and its underlying mechanisms.

METHODSThe cytotoxic effect of DMF on PC3 cells was measured by MTT assay. Induction of apoptosis was assessed by propidium iodide staining and flow cytometric analysis. Changes of mitochondrial membrane potential (DeltaPsim) were detected by JC-1 staining. The levels of apoptosis related proteins were analyzed by Western blot.

RESULTSDMF exhibited high efficiency on cell growth inhibition in PC3 cells with an IC50 value of (9.5 +/- 0.2)micromol/L. Flow cytometric analysis indicated that DMF could induce apoptosis in PC3 cells. A significant decrease of mitochondrial membrane potential was observed in PC3 cells treated with DMF, which was in a time- and dose-dependent manner. The results of Western blot indicated that DMF induced the activation of caspase-3, increased the ratio of Bax/Bcl-2 and downregulated the expression of phosphate-p38.

CONCLUSIONDMF is a potential compound against PC3 cells and the mitochondrial pathway might be involved in DMF-induced apoptosis in PC3 cells.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chlorobenzenes ; pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; drug effects ; Flavonoids ; pharmacology ; Flow Cytometry ; Growth Inhibitors ; pharmacology ; Humans ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Piperidines ; pharmacology ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

To study the interaction of drugs of different properties, namely puerarin, borneol and catalpol in the process of in- clusion, in order to explore the inclusion regularity of multi-component and multi-property traditional Chinese medicine compound in- clusions. With HP-β-CD as the inclusion material, the freeze-drying method was used to prepare the inclusion. The inclusion between puerarin, borneol and catalpol was tested by measuring the inclusion concentration, DSC and X-ray diffraction. According to the find- ings, when insoluble drugs puerarin and borneol were included simultaneously, and puerarin was overdosed, puerarin included was almost equal to puerarin included, and borneol was not included. When puerarin was under-dosed, and HP-β-CD was overdosed, borne- ol was included, and the simultaneous inclusion was lower than the separate inclusion of borneol. When water-soluble drug catalpol was jointly included with puerarin or borneol, the simultaneous inclusion was almost the same with their separate inclusion, without charac- teristic peak of catalpol in DSC and X-ray diffraction patterns. There is a competition in the simultaneous inclusion between water-solu- ble drugs puerarin and borneol and a stronger competition in puerarin. The water-soluble drug catalpol could be included with HP-β-CD with no impact on the inclusion of puerarin or borneol.
2-Hydroxypropyl-beta-cyclodextrin ; Bornanes ; chemistry ; therapeutic use ; Brain Ischemia ; drug therapy ; Drug Compounding ; methods ; Freeze Drying ; Iridoid Glucosides ; chemistry ; therapeutic use ; Isoflavones ; chemistry ; therapeutic use ; Solubility ; beta-Cyclodextrins ; chemistry

ObjectiveTo explore the relations between the alkaline phosphatase(ALP) and the type of cerebral palsy. MethodsThe ALP level of 40 children with different types of cerebral palsy were examined with the Olympus AU-600 apparatus. ResultsThe ALP value of the children with spastic cerebral palsy is normal. The ALP value of the children with athetoid cerebral palsy is higher than spastic cerebral palsy(P<0.001).Conclusions The ALP value can help us to identify the type of cerebral palsy.

Objective:To assess the efficacy and the safety of the radiofrequency catheter ablation (RFCA) for the septal accessory pathway (AP) in children.Methods:From September 2013 to March 2019, 626 patients plan to underwent RFCA for paroxysmal supraventricular tachycardia (PSVT) in Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.Among them, 74 consecutive patients with right or left septal APs were included in the study and their clinical and RFCA data were analyzed.Results:The age of these 74 children (45 males, 29 female) was (7.8±3.5) years, ranging from 10 months to 13 years.The body weight (BW) was (27.7±14.4) kg, with 3 patients BW<15 kg.A discordant ventricular wall motion (DVWM) was found in 5 patients, and the combined congenital heart diseases were discovered in 2 patients.A three dimensional mapping system was applied in 69 ablations, and 3 ablations were performed only with the fluoroscopy monitor of 5 cases.According to the AP location, the number of cases located in the anteroseptal, the midseptal, the mouth of coronary sinus, the left posteroseptal and the right posteroseptal, were 28, 18, 10, 10 and 8, respectively.The ablation operations were applied in 72 patients.The initial acute success reached in 67 (93.1%) patients.The ablation energy was (18.0±1.8) W, the fluoroscopy time during the ablations was (4.7±2.7) minutes, and the procedure duration was (151.5±58.6) minutes.One inadvertent complete atrioventricular block (AVB) was noted as the ablation-related complication.All 5 children with the pre-DVWM were recovered after ablations.During a follow-up of (23.8±10.8) months, 4 patients experienced the recurrence of preexcitation syndrome atrioventricular reentrant tachycardia.Conclusions:With the 3D-mapping system, the RFCA of septal APs can be performed safely and effectively in pediatric patients of paroxysmal supraventri-cular tachycardia.However, as the ablation-related complication, AVB should not be ignored.

OBJECTIVEPrader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome. The purpose of this study was to show the molecular genetic defects and genomic imprinting basis in Chinese PWS patients and to evaluate the clinical applications of a differential diagnostic test for PWS.

METHODSFluorescence in situ hybridization (FISH) and methylation-specific PCR (MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using three probes, including SNRPN probe for identification of the critical locus in PWS region, D15Z1 and PML control probes for identification of the 15p arm and 15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on sodium bisulfite treatment of DNA and PCR primers specific for the maternal and paternal allele.

RESULTSWhen hybridized with mixed probes, it was found in 2 patients that the central specific signal was absent, but both the flanking control signals were retained, indicating SNRPN gene deletion of chromosome 15q11-13. Bisulfite-modified DNA from all PWS children amplified with methylated allele-specific primer pair showed only maternal 131bp PCR product, indicating the maternal uniparental disomy (UPD15).

CONCLUSIONGenomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other cyto-molecular tests and its results were consistent with the clinical diagnosis of PWS, so it seems to be a reliable diagnostic method for PWS patients who show abnormal methylation at SNRPN. The genetic differential tests for PWS are important in determining familial recurrence risk.

Adolescent ; Autoantigens ; Chromosome Deletion ; Chromosomes, Human, Pair 15 ; genetics ; Gene Deletion ; Genomic Imprinting ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymerase Chain Reaction ; methods ; Prader-Willi Syndrome ; genetics ; Ribonucleoproteins, Small Nuclear ; genetics ; snRNP Core Proteins

This paper introduced an experimental study of polylacticacid (PLA) nanoparticles of lipophilic anti-cancer herb drug using a precipitation method. Cucurbitacins (Cu) and Curcuminoids (Cur) were selected to be model drugs. They had similar solubility but their incorporation effects were significantly different: the average drug entrapment ratio, the average drug loading and the average drug recovery were 38.53%, 2.21% and 27.02% respectively; while those of Cur-PLA-NP were 94.36%, 14.35% and 91.23% respectively. To analyse the reason, drug incorporation process was investigated. By measuring solvent evaporation rate, ratio of drug PLA precipitates, drug distribution in system and entrapping ratio at different time of preparation, we found the difference of precipitation velocity of drug was the main reason. We also concluded that not all lipophilic drug can be well entrapped into PLA nanoparticle by nanoprecipitation method. The drug incorporation depended on the interations among drug, PLA and organic solvents, in addition to the solubility of the drug.
Antineoplastic Agents, Phytogenic ; chemistry ; Chemical Precipitation ; Cucurbitacins ; chemistry ; Curcumin ; chemistry ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; Lactic Acid ; chemistry ; Nanoparticles ; Nanotechnology ; methods ; Particle Size ; Polyesters ; Polymers ; chemistry

The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.
Acetaminophen ; chemistry ; Chromatography, Affinity ; Drug Interactions ; Kinetics ; Mass Spectrometry ; Thermodynamics ; Thiazines ; chemistry ; Thiazoles ; chemistry ; beta-Cyclodextrins ; chemistry