Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.
Acetaminophen ; administration & dosage ; chemistry ; Administration, Oral ; Drug Delivery Systems ; Electrical Equipment and Supplies ; Electrochemical Techniques ; instrumentation ; methods ; Hydrogen Bonding ; Kinetics ; Lipids ; chemistry ; Microspheres ; Solubility ; Taste ; drug effects ; beta-Cyclodextrins ; chemistry

Autophagy is a self-decomposing process that is used to degrade long-lived proteins or necrotic organelles.It is extremely dependent on lysosomes,widely present in eukaryotic cells and highly conserved.Autophagy can protect the cells themselves and help them resist the adverse environment at a proper level,but excessive autophagy can result in autophagic cell death.In recent years,with the comprehensive research of autophagy,it has been found that autophagy is closely related to the development and progression of most tumors.More drugs associated with autophagy are used for the clinical treatment of tumors,but they have different therapeutic effects on different tumors,so the impact of autophagy-related drugs on normal cells need to be identified through more clinical trials and experimental studies.This paper reviews the roles of autophagy in the occurrence and development of tumors,and recent progress in the treatment of cancer by regulating autophagy through drugs.

OBJECTIVETo follow the fate of murine epidermal stem cells (ESCs) seeded in a syngeneic dermal equivalent implanted in vivo.

METHODSEmbryonic stem (ES) cells were induced in vitro to differentiate into ESCs. After stained with a fluorescent dye Hoechst 33342, these ESCs were seeded into a fibroblast-collagen-gelatin sponge complex, functioning as a dermal equivalent model, and implanted subcutaneously into 129/J mice, which were syngeneic to these stem cells. The fate of these cells was observed with HE staining, immunocytochemical staining or Van Gieson's staining.

RESULTSThese ESCs were clearly visible in the implant by fluorescent microscopy 3 weeks or longer after implantation. These cells remained viable, differentiated into hair follicle-like structure, glandular structure, and gave rise to additional structures displaying features resembling native dermis. A number of markers were expressed in the differentiated structures, including CD29 (integrin beta1 subunit) and cytokeratin 18 (CK18). No apparent rejection or severe side effects were observed at least during the 10 weeks following implantation.

CONCLUSIONNow that ESCs could survive in vivo in this dermal equivalent model, and differentiate into hair follicle-like structures as well as glandular structures, it is feasible to use these cells as seed cells in the study to fabricate dermal equivalent having the potential to develop dermal appendages.

Animals ; Cell Culture Techniques ; Cells, Cultured ; Dermis ; cytology ; transplantation ; Embryonic Stem Cells ; cytology ; Epithelial Cells ; cytology ; Mice ; Mice, Inbred Strains ; Skin Transplantation ; Stem Cell Transplantation ; Stem Cells ; cytology ; Tissue Engineering

OBJECTIVETo assess the clinical value of three-dimensional contrast-enhanced magnetic resonance angiography (3D-CE-MRA) in the diagnosis of mesenteric arteriosclerosis.

METHODS3D-CE-MRA of the mesenteric arteries was performed in 21 patients with 23 healthy subjects as the control. After 3D image reconstruction and maxi intense projection, and the abnormalities of the mesenteric arteries were observed and analyzed. The diameter and number of the arterial branches were compared between the patients and the control subjects.

RESULTSAll the 21 patients suffered arteriosclerosis in the arteries other than the mesenteric arteries. On 3D-CE-MRA, mesenteric arteriosclerosis was characterized by thinning of the arterial trunk, luminal stenosis, irregular arterial margins and homo- or heterogeneous thickening of vascular walls. Multiple filling defects were found in the mesenteric artery lumens with reduced second order branches, which showed rigid lining with dashed line appearance or disappeared in some cases. The inferior mesenteric arteries were seen in only 2 patients. The diameters of superior and inferior mesenteric arteries were 3.8-/+0.32 mm and 1.20-/+0.12 mm in the patients, significantly smaller than those of in the control subjects (6.51-/+1.01 mm and 2.90-/+0.90 mm, respectively, P<0.01). The number of the mesenteric artery branch of the patients was also significantly reduced as compared with that in the control subjects (P<0.05). In som cases, the intestinal enhancement was attenuated with the intestinal contraction, dilatation and lowering of the intestinal tension.

CONCLUSION3D-CE-MRA can clearly display mesenteric arteriosclerosis and secondary intestinal changes, and provides a useful means for the diagnosis and assisting the therapy of mesenteric arteriosclerosis.

Aged ; Aged, 80 and over ; Arteriosclerosis ; diagnosis ; pathology ; Case-Control Studies ; Contrast Media ; Female ; Humans ; Image Enhancement ; Imaging, Three-Dimensional ; Magnetic Resonance Angiography ; methods ; Male ; Mesenteric Arteries ; pathology ; Middle Aged

BACKGROUNDSoft tissue rheumatism is a group of common rheumatic disorders reported in many countries. For investigating the prevalence rate of soft tissue rheumatism in different population in China, we carried out a population study in Shantou rural and Taiyuan urban area.

METHODSSamples of 3915 adults in an urban area of Taiyuan, Shanxi Province, and 2350 in a rural area of Shantou, Guangdong Province were surveyed. Modified International League of Association for Rheumatology (ILAR)-Asia Pacific League of Association for Rheumatology (APLAR) Community Oriented Program for Control of Rheumatic Diseases (COPCORD) core questionnaire was implemented as screening tool. The positive responders were then all examined by rheumatologists.

RESULTSPrevalence rate of soft tissue rheumatism was 2.0% in Taiyuan, and 5.3% in Shantou. Rotator cuff (shoulder) tendinitis, adhesive capsulitis (frozen shoulder), lateral epicondylitis (tennis elbow), and digital flexor tenosynovitis (trigger finger) were the commonly seen soft tissue rheumatism in both areas. Tatarsalgia, plantar fasciitis, and De Quervain's tenosynovitis were more commonly seen in Shantou than that in Taiyuan. Only 1 case of fibromyalgia was found in Taiyuan and 2 cases in Shantou. The prevalence of soft tissue rheumatism varied with age, sex and occupation.

CONCLUSIONSSoft tissue rheumatism is common in Taiyuan and Shantou, China. The prevalence of soft tissue rheumatism was quite different with different geographic, environmental, and socioeconomic conditions; and varying with age, sex, and occupation. The prevalence of fibromyalgia is low in the present survey.

Adolescent ; Adult ; Age Distribution ; Aged ; Bursitis ; epidemiology ; China ; epidemiology ; Humans ; Middle Aged ; Rheumatic Diseases ; epidemiology ; Sex Distribution ; Tendinopathy ; epidemiology ; Tenosynovitis ; epidemiology ; Young Adult

OBJECTIVETo evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains.

METHODSGenomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software.

RESULTSThe Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. bovis and M. africanum strains from the four loci.

CONCLUSIONWe have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.

Cluster Analysis ; Genotyping Techniques ; Humans ; Minisatellite Repeats ; Mycobacterium bovis ; genetics ; Mycobacterium tuberculosis ; genetics

AIM: To investigate the possible signaling pathway that promotes epithelial-mesenchymal transi-tion(EMT)of the lung cancer A549 cells stimulated with muscarinic receptor 3(M3R)agonist carbachol.METHODS:The lung cancer cells A549 were treated with 400 μmol/L carbachol.The morphological changes of the cells were observed under inverted phase contrast microscope.The migration and invasion abilites were measured by Wound healing and Tran-swell assays.qPCR was used to detect the mRNA level of vimentin and E-cadherin.The protein levels of p-AKT,vimentin and E-cadherin were determined by Western blot.RESULTS:After treatment with carbachol,the A549 cells showed loss of the close connection and the cell morphology was transformed from irregular polygon to spindle -like cells.The results of Wound healing and Transwell assays showed that the migration and invasion abilites of the A 549 cells were enhanced.Car-bachol increased the vimentin expression and decreased the E-cadherin expression at mRNA and protein level(P<0.05). The phosphorylation of AKT in the A549 cells was up-regulated(P<0.05).These changes was inhibited by M3R antago-nist 4-DAMP.CONCLUSION:Carbachol promotes EMT in the human lung cancer A 549 cells by activating PI3K/AKT signaling pathway.

Objective To investigate the effects of 3 different ventilation methods,including conventional mechanical ventilation(CMV),high-frequency oscillatory ventilation(HFOV) and partial liquid ventilation(PLV),on the morphology of type Ⅱ alveolar epithelium cell (ACE Ⅱ) of newborn piglet with acute lung injury (ALI).Methods Twenty-four less than 3-day-old newborn piglets were enrolled.After ALI was established with saline lavage (38 ℃,0.035 L/kg),newborn piglets were randomly assigned to 4 study groups:control group(n =6,no ventilation),CMV group(n =6),HFOV group(n =6),and PLV group(n =6,38 ℃,0.018 L/kg).Piglets in the 4 groups were sacrificed after being ventilated for 24 hours,and the number,area,density of fluorescence of ACE Ⅱ were detected.Results Through 24 hours mechanical ventilation,the numbers of ACE Ⅱ in CMV group,HFOV group and PLV group remained were 30 ± 5,52 ± 5,81 ± 7,respectively,while areas of fluorescence were 340.40 ± 47.50,329.69 ± 124.50,295.55 ± 109.30,respectively,and there were significant differences among the 3 groups,and the population mean of density of fluorescence had significant difference among the 3 groups.The number of ACE Ⅱ remains was lowest in CMV group compared with HFOV group(P =0.026) and PLV group (P =0.000),and the density of fluorescence of ACE Ⅱ was lowest in CMV group compared with HFOV group (P =0.001) and PLV group (P =0.002).Conclusions Different mechanical ventilations have various effects for ACE Ⅱ,and CMV is the most harmful mechanical ventilation on ACE Ⅱ,while PLV is the least harmful.

OBJECTIVETo investigate the feasibility of tracheal reconstruction with a prosthesis made of memory alloy coated with collagen sponge in mongrel dogs.

METHODThe basic skeleton of the prosthesis was knitted with Ni-Ti memory alloy wires. The tubular mesh was sealed with polyurethane membrane and then inner and external walls of the lumen were coated with collagen sponge. Cervical trachea segmental reconstruction was performed in 8 mongrel dogs with these prostheses. The efficacy of the implanted prostheses were periodically evaluated after operation using x-ray, tracheoscopy and specimen microscope examinations.

RESULTSOne dog died of prosthesis dislocation 10 days after operation, another was killed 45 days later because of anastomotic stenosis. 6 dogs survived more than 90 days and the longest one lived for 150 days. Its implanted prosthesis was completely incorporated with the recipient tissue, where re-epithelialization occluded on anastomotic sites. The tracheal lumen was patent.

CONCLUSIONThis memory alloy tracheal prosthesis has been proved useful for reconstruction of large, circumferential tracheal defects, although its long-term safety and efficiency need to be confirmed.

Alloys ; Animals ; Artificial Organs ; Collagen ; Dogs ; Prosthesis Design ; Trachea

OBJECTIVE: To establish an indicator system for risk assessment on occupational dust hazards and verify its application. METHODS: Using Delphi method,two rounds of investigation were made from 30 experts who work on frontline occupational health. The indicator system for risk assessment was established based on the investigation,statistics and boundary value,in fully consideration with the interaction of three basic elements of“dust inherent characteristics-laborers factors-influencing factors”. The indicator system was applied to evaluate the risk of 90 workplaces in the presence of dust occupational risk factors. RESULTS: The positive coefficient of experts' opinion was 90%,and the coefficient of experts' authority was 0. 808. The coefficient of experts' consensus was 0. 50( χ~2= 120. 56,P < 0. 01). The indicator system for risk assessment on occupational hazards of dust factors has been successfully established. This system included three class A indicators,nine class B indicators and twenty-eight class C indicators. The total coincidence rate of assessments on the risk level of occupational dust hazards of workplaces was 60%( Kappa = 0. 452,P < 0. 01). CONCLUSION: This indicator system was objective,scientific and feasible,and could reflect the actual levels of occupational dust hazards.