Microtubule is one of the key components of the cytoskeleton and plays an important role in the maintenance of cell shape and the process of signal transduction and mitosis. Due to the extreme importance of microtubule in the process of mitosis, tubulin becomes one of the most important targets for development of new anticancer drugs and tubulin inhibitors are used for the treatment of cancer nowadays. These inhibitors have antitumor activity by inhibiting or promoting the assembly of tubulin to microtubules and interfering the process of cell mitosis. This review summarized the research progress of the tubulin inhibitors, especially the introduction of the tubulin inhibitors of pharmacological activities and the progress of clinical research. Also, the development trend of these inhibitors is discussed.

Objective To research on the applicational value of quantitative immunofluorescence assay of high-sensitivity C- reactive protein(HS-CRP) detection in surveillance of ankylosing spondylitis(AS) and Rheumatoid arthritis(RA).Methods Using quantitative immunofluorescence technique to detect the serum HS-CRP among 43 patients with AS and 62 patients with RA and 30 healthy controls.Results Within-run CV% of repeatability were 4.98% and3.68% for lower and higher concentration of HS- CRP,respectively;between-run CV% of the stability were 4.57% and 5.42% for lower and higher concentration of HS-CRP, respectively;There was a good correlation between results of quantitative immunofluorescence assay and BNP special protein analyzer method(r=0.997);Both the level and the positive rate of HS-CRP of patients with AS and patients with RA were higher than those of the controls in the active phase.The level and the positive rate of HS-CRP in patients with AS and patients with RA were obviously higher in the active phase than in the non-active phase(P0.05).Conclusion There were significant correlations between HS-CRP and the activity of AS and RA,So HS-CRP was useful tools for monitoring the changes of patient's condition.It doesn't have much significance in differential diagnosis of AS and RA.

Objective To study interleukin-1 receptor(IL-1R) and connexin(Cx36) gene expression following Mg 2+-free-induced seizures in cultured developing neuron. Methods Rat embryo cortical neurons cultured for 6 and 17 days were exposed to Mg 2+-free media to induce seizure. At different time after Mg 2+-free treatment, real-time RT-PCR was used to detect IL-1R and Cx36 mRNA expression. Results 1. IL-1R mRNA expression transiently decreased after Mg 2+-free treatment in neurons cultured for 6 and 17 days in vitro. Then the levels of IL-1R mRNA expression recovered in neurons cultured for 6 days, but IL-1R mRNA expression were increased in neurons cultured for 17 days compared with control group and the peak was at 24 hours. 2. In neurons cultured for 6 days in vitro, Cx36 mRNA expression increased after Mg 2+-free treatment compared with control group, the peak was at 24 hours. But in neurons cultured for 17 days in vitro, Cx36 mRNA expression decreased at 6 hours after Mg 2+-free treatment compared with control group, the peak was at 24 hours. Conclusions IL-1R mRNA and Cx36 mRNA expression following Mg 2+-free-induced seizures are different between the neurons cultured for 6 and 17 days in vitro. This is possibly related to the different neuron injury between 6 and 17 days in vitro following seizures.

Objective To explore the effect of aminolevulinic acid-based photodynamic therapy(ALA-PDT) on alloreactived peripheral blood mononuclear cells(PBMCs).Methods Human PBMCs from different healthy donor were collected and mixed in the one-way mixed lymphocyte culture(MLC) for 5 days. The cells were harvested and aminolevulinic acid(ALA) were added into ALA group and ALA+Light group with ultimate concentrations of 0.5 mmol/L,1.0 mmol/L,1.5 mmol/L,2.0 mmol/L and 2.5 mmol/L.After cultured for 2 hours, 4 hours and 6 hours respectively in 37 ℃ 5% carbon dioxide incubator,Light group and ALA+Light group were irradiated by light of 410 nm wavelength for 1 hour.The MLC cells were treated with the former stimulator cells for 48 hours.The survival of stimulator cells were detected using MTT colorimetric assay and the kill rates of treated cells were calculated.Results The kill rate of ALA+Light group on stimulators was apparently lower than those of Light group, ALA group and control group, (33.0?26.5)% vs (87.1?2.2)%,(89.2?2.5)%,(90.3?1.9)%(All P

Objective To evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in sevoflurane postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in mice.Methods Forty pathogen-free healthy male C57 mice,aged 8 weeks,weighing 20-30 g,were assigned into 4 groups (n=10 each) using a random number table:sham operation group (group Sham),myocardial I/R group (group I/R),sevoflurane postconditioning group (group SPC) and HIF-1α inhibitor 2Me2 group (group 2Me2).Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min of reperfusion in pentobarbital sodium-anesthetized mice.In group SPC,3％ sevofiurane was inhaled for 15 min starting from the onset of reperfusion.In group 2Me2,30％ 2Me2 (30 mg/kg) was intraperitoneally injected at 30 min before ischemia.The mice were sacrificed at the end of reperfusion,and the hearts were removed for determination of the myocardial infarct size (using the Image J software) and expression of HIF-1α in thc nucleus of cardiomyocytes (by Western blot).Results Compared with group Sham,the myocardial infarct size was significantly increased in I/R,SPC and 2Me2 groups,the expression of HIF-1α was significantly up-regulated in I/R and SPC groups,and the expression of HIF-1α was significantly down-regulated in group 2Me2 (P＜ 0.05).Compared with group I/R,the myocardial infarct size was significantly decreased,and the expression of HIF-1α was up-regulated in group SPC,and the myocardial infarct size was significantly increased,and the expression of HIF-1α was down-regulated in group 2Me2 (P＜0.05).Compared with group SPC,the myocardial infarct size was significantly increased,and the expression of HIF-1α was down-regulated in group 2Me2 (P＜0.05).Conclusion The mechanism by which sevoflurane postconditioning reduces myocardial I/R injury is related to up-regulation of HIF-1α expression in mice.

OBJECTIVETo investigate the therapeutic efficacy and adverse reactions of Aidi Injection (AI) combined with percutaneous cool-tip radiofrequency ablation (CRFA) in treatment of primary liver cancer and to explore its effect on immune function.

METHODSEighty-nine patients with primary liver cancer at middle-late stage were assigned to the control group with CRFA alone and the treatment group treated with CRFA and intravenous dripping of AI 50 mL once every day for succesive 20 days.

RESULTSCompared with those before treatment, the alanine aminotransferase (ALT) and albumin (ALB) levels showed no marked change, and CD4 subgroup of T lymphocyte and CD4/CD8 ratio elevated in the treatment group (P<0.01), while the ALT level elevated (P<0.05), ALB level decreased (P < 0.01), CD4 and CD4/CD8 ratio showed no change in the control group. The relapse rate was 20.0% (3/15) in patients with tumor more than 3 cm in diameter of the treatment group, which was obvious lower than that in the control group (55.0%, 11/20, P < 0.05).

CONCLUSIONAI treatment could relieve the impairment of CRFA on hepatic function, improve immune function and reduce relapse rate in patients with primary liver cancer.

Adult ; Aged ; CD4-CD8 Ratio ; Carcinoma, Hepatocellular ; immunology ; therapy ; Catheter Ablation ; methods ; Combined Modality Therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Humans ; Infusions, Intravenous ; Liver Neoplasms ; immunology ; therapy ; Male ; Middle Aged ; Phytotherapy ; Treatment Outcome

OBJECTIVETo investigate the effects of non-neuronal muscarinic receptors (NNMR) stimulation on atherosclerosis and endothelial cells activation.

METHODSAtherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 weeks. During the experimental periods, animals were received a low (7 mg/kg/d) or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the treatments, serum total cholesterol and NO levels were measured, and the aorta morphology was analyzed by hematoxylin and eosin staining. The gene expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in the thoracic aortas was determined by RT-PCR, and the MCP-1 protein expression and NF-κB activity were detected by Western blot analysis. NO production, MCP-1 secretion in cultured rat aortic endothelial cells (RAECs), and monocyte-endothelium adhesion assay were also performed after arecoline treatments.

RESULTSArecoline efficiently decreased atherosclerotic plaque areas, increased serum nitric oxide (NO) content, suppressed the mRNA and protein expression of MCP-1, and modulated the IκB-α degradation and P65 phosphorylation in the aortae of ApoE-/- mice. Furthermore, arecoline promoted NO production and suppressed MCP-1 secretion in cultured RAECs after ox-LDL exposure, and either atropine or NG-nitro-L-arginine methylester could abrogate these effects. Arecoline also significantly inhibited the adherence of U937 monocytes to the ox-LDL injured human umbilical vein endothelial cells, which could be abolished by atropine.

CONCLUSIONOur results indicate that arecoline attenuates the progression of atherosclerosis and inhibits endothelial cells activation and adherence by stimulating endothelial NNMR. These effects, at least in part, are due to its modulation on NF-κB activity.

Animals ; Aorta ; cytology ; Apolipoproteins E ; Arecoline ; pharmacology ; Atherosclerosis ; physiopathology ; prevention & control ; Cell Adhesion Molecules ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Disease Progression ; Endothelial Cells ; cytology ; drug effects ; Endothelium, Vascular ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; I-kappa B Proteins ; metabolism ; Lipoproteins, LDL ; Mice ; Mice, Knockout ; Monocytes ; cytology ; NF-KappaB Inhibitor alpha ; Nitric Oxide ; blood ; Nitroarginine ; pharmacology ; Rats ; Receptors, Muscarinic ; physiology ; Transcription Factor RelA ; metabolism

Angiography, Digital Subtraction ; Cranial Nerve Neoplasms ; diagnosis ; diagnostic imaging ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Paraganglioma ; diagnosis ; diagnostic imaging ; surgery ; Vagus Nerve Diseases ; diagnosis ; diagnostic imaging ; surgery

AIMTo study the erosion behaviour during dissolution of matrices using different molecular weight polyethylene oxide (PEO) as hydrophilic polymer.

METHODSPEO hydrophilic matrix tablets with no added drug and excipients were prepared by direct compression method. The erosion rates of matrices comprised of pure or blending PEO polymers were evaluated in distilled water at (37 +/- 0.5) degrees C with rotating rate of 50 r x min(-1). The relationship between PEO molecular weight and erosion rate of matrices was investigated by experimental and mathematical model methods.

RESULTSThe gravimetric erosion experimental results indicated that the power-law relationship which relates the polymer erosion rate and weight average molecular weight: k infinity (M(w)) -1.30 4 was proved to have great potential utility in predicting the degree of polymer erosion of matrices comprised of either intermediate molecular weight (97. 98 x 10(4) - 553. 36 x 10(4)) or blends of lower and higher molecular weight polymers. Based on the semiempirical equation for mass transfer rate: Jp = (fp < Dp > (2/3) v (-1/6) omega (1/2)) C(p,dis), a theoretical mathematic model was developed for describing the relationship between PEO erosion rate and PEO weight average molecular weight: Jp infinity M(-1.241), where the exponent of -1. 241 was very close to the exponent of - 1. 130 4 obtained from practical determination.

CONCLUSIONPEO was proved to be a good candidate of hydrophilic polymer and appeared to have great potential for controlled release applications. The mathematic model presented together with the utilization of the erosion behaviour discussed in our study could provide a guide line to predict the degree of polymer erosion for other intermediate polymer grades and / or mixture of the polymers utilized in this study, which could play an active role in designing PEO hydrophilic sustained delivery systems.

Delayed-Action Preparations ; chemistry ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Drug Stability ; Excipients ; chemistry ; Molecular Weight ; Polyethylene Glycols ; administration & dosage ; chemistry ; Polymers ; Solubility ; Tablets ; Water

OBJECTIVETo study the psychologic status and their influencing factors in congenital microtia patients and their families.

METHODSTotally one hundred and two congenital microtia patients (79 men, 23 women, mean age 13.62 +/- 7.2 years) were enrolled. The patients and their families answered the questionnaire written by ourselves to identify the psychosocial problems.

RESULTS(1) 23.5% patients were found to have severe psychosocial problems, such as lack of self-confidence, close and fear and so on. (2) With the growth of age, psychosocial problems of the patients were rated high (P < 0.05). (3) For patients who found their deformations early, psychosocial problems also were rated low. (4) For patients who found their deformations by themselves, psychosocial problems also were rated low. (5) The education and psychosocial impact for parents all affected patients deeply.

CONCLUSIONSTo prevent psychosocial problems, we should operate for patients as early as possible. And correct guidance is very important for youngsters.

Adolescent ; Adult ; Child ; Child, Preschool ; Congenital Abnormalities ; epidemiology ; psychology ; Ear ; abnormalities ; Family ; psychology ; Female ; Humans ; Inpatients ; statistics & numerical data ; Male ; Surveys and Questionnaires ; Young Adult