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 study the effect of early enteral nutrition(EN) and total parenteral nutrition(TPN) in patients with severe acute pancreatitis by a mata analysis.Methods Randomized controlled trials of TPN and early EN in patients with severe acute pancreatitis were searched in Medline,Pubmed and Embase from Jan 1970 to June 2009,and Cochrane Library(Issue 2,2009).Seven studies were enrolled into the analysis.The detail about the trial design,characters of the subjects and results of the studies were reviewed by two independent authors and analysed by using Revman 5.0.18 software.Results Compared with TPN,early EN was associated with a significantly lower incidence of pancreatic infections(OR =0.38,95% CI :0.18～0.82,P =0.01),organ failure(OR =0.43,95% CI :0.23～0.79,P =0.007),fewer surgical interventions(OR =0.34,95% CI :0.18～0.63,P =0.0006) and mortaily(OR =0.41,95% CI :0.19～0.88,P =0.02).However,there was no significant difference in total infections [ OR =0.43,95% CI(0.17,1.10),P =0.08]between patients with TPN and early EN.Conclusions Early EN could be the preferred nutrition feeding method for patients with severe acute pancreatitis.

Objective To observe the effect of Sini decoction on inflammatory response and immune function in septic rats and to discuss its possible mechanism.Methods 66 Sprague-Dawley (SD) rats were randomly divided into normal control group (n=6),model group (n=30),and Sini decoction group (n=30).Septic model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS,5 mg/kg).After the reproduction of sepsis,rats in Sini decoction group received Sini decoction (5 g/kg) by gavage,while those in model group were given equal dose of normal saline in the same way.Rats in normal control group did not receive any treatment.Blood was collected via eye sockets at 2,12,24,48,72 hours after LPS administration,then the rats were sacrificed.The concentrations of inflammatory mediators,such as interleukin (IL-1,IL-6,IL-10),tumor necrosis factor-α (TNF-α),and the expression level of monocyte human leukocyte antigen-DR (HLA-DR) were determined with enzyme linked immunosorbent assay (ELISA),and the pathological changes in intestinal mucosa were observed under electron microscope.Results The concentration of IL-1 (ng/L) at 2 hours in model group was gradually increased and peaked at 48 hours (4.07 ± 0.10),and then gradually decreased,while the IL-1 level in Sini decoction group peaked at 12 hours (2.98 ± 0.12) followed by a gradual decrease.IL-6 (ng/L) in model and Sini decoction groups peaked twice at 12 hours (91.39 ± 1.55,73.00 ± 2.38) and 48 hours (82.51 ± 1.49,64.68 ± 1.68) respectively.IL-10 (ng/L) in model group gradually decreased after peaking at 2 hours (86.66 ± 6.12),and that in Sini decoction decreased at 12 hours (71.61 ± 2.35) followed by an increasing tendency,and approached normal level at 48 hours (109.09 ±4.77 vs.124.01 ± 7.89,P＞0.05).TNF-α (ng/L) in model group was gradually increased and peaked at 48 hours (83.37 ±3.79),and that in Sini decoction peaked at 12 hours (48.52 ± 1.21),and decreased to normal level at 72 hours (18.59 ± 1.97 vs.15.50 ± 2.68,P＞0.05).During the course of the experiment,as compared with those of the model group,level of IL-1,IL-6,and TNF-α were significantly lower at all time points in Sini decoction group,and IL-10was significantly higher.The expression level of HLA-DR (μg/L) in model and Sini decoction groups peaked at 2 hours (4.86 ± 0.15,4.85 ± 0.17),and then gradually lowered.HLA-DR expression μg/L) at 48 hours and 72 hours in Sini decoction group was significantly lower than that in model group (48 hours:4.21 ± 0.12 vs.2.74 ± 0.16,72 hours:3.80 ± 0.09 vs.2.27 ± 0.12,both P＜0.01).Pathological study of intestinal mucosa showed that the intestinal mucosa were infiltrated significandy by inflammatory cells,and villi were damaged severely in both model group and Sini decoction group at 2 hours after LPS challenge.Infiltration of inflammatory cells in Sini decoction group was less intense after 12 hours,and the intestine villi repair was more obvious compared with model group.Conclusion Sini decoction could regulate systemic inflammatory response,and promote the repair of intestinal mucosa,the intestinal function and the immune status of septic rats.

Objective To construct the transmembrane TNF-? eukaryotic expression vector in n-3 PUFA dependant manner. Methods PPRE-tk sequence was designed and artificially synthesized, and then inserted it into pcDNA3-TNF( ? 1-12)WB plasmid to construct eukaryotic expression vector pPPRE-tk-tmTNF-? by gene recombine techniques. The tmTNF-? protein expression level was observed in MCF-7 transfected cells incubated with EPA by immunofluorescence technique. Results pPPRE-tk-tmTNF-? expression vector was constructed successfully and identified by agarose gel electrophoretic analysis and nucleotide sequence analysis. EPA could increase tmTNF expression levels in time- and dose-dependant manners. Conclusion tmTNF-? expression vector regulated by n-3 PUFA is successfully constructed.

Objective To study the enhancing effect of ultrasound plus microbubble on small interference RNA(siRNA)transfection in vitro and in vivo.Methods Human vascular epithelial growth factor(VEGF)siRNA with 2'deoxy modification(VEGF 2'-eoxy siRNA,VdsR)was used.The human CNE cells(fromnasopharyngeal carcinoma)line was used for in vitro cell-based experiments and in vivo mouse xenograft model.Two different microbubble agents.BR14 and Levovist.were used together with the RNA transfection reagent RNA-mate.ELISA and RT-PCR assays were used to assess VEGF gene expression.Immunohistochemical staining (IHC)was performed to assess CD31 expression in xenograft tumors.Results VdsR transfection in CNE cells abolished VEGF expression as determined by ELISA experiments.In the first mouse xenograft experiment,ultrasound exposure dramatically enhanced VdsR-mediated tumor inhibition.In the second mouse xenograft experiment,when VdsR was mixed with the microbubble reagents and then injected into xenografts,ultrasoundexposure significantly reduced tumor growth in BR14-mixed VdsR group but not in the Levovist-mixed VdsR group compared to the control.RT-PCR experiments demonstrated that VEGF expression in ultrasound-exposed tumors was significantly lower than that in the control.Meanwhile,VEGF expression in the tumor tissue treated by BRl4-mixed VdsR declined as compared with the controls.Tumor vascular density as measured by CD31 immunostaining was significantly decreased in ultrasound-exposed tumors compared to the control.Conclusions Ultrasound exposure and/or microbubble can significantly enhance delivery and the efficiency of VdsR-mediated anti-tumor effects,and should be a location-specific enhancement approach for siRNA-based anti-cancer therapy.

Objective: To investigate the mechanisms of electroacupuncture (EA) at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) in intervening diabetic gastroparesis (DGP) based on calcium-activated chloride channel. Methods: Forty Sprague-Dawley rats were randomly divided into four groups, including a normal control group (group A), a model group (group B), an EA group (group C) and a metoclopramide group (group D), with 10 rats in each group. A single intraperitoneal injection of 2％ streptozotocin (STZ) combined with 8-week high-glucose high-fat diet was used to establish a DGP rat model. After intervention, gastrointestinal propulsive rate was observed; the expression level of transmembrane protein 16A (TMEM16A) was examined by immunohistochemistry; the Ca2+ concentration in interstitial cells of Cajal (ICCs) was detected by immunofluorescence; and whole-cell patch-clamp technique was applied to detect the current intensity of calcium-activated chloride channel (ICaCC) in ICCs in gastric antrum. Results: After modeling, the blood glucose levels in group B, group C and group D were significantly increased compared with group A (all P<0.01); after intervention, compared with group B, the blood glucose levels in group C and group D were significantly decreased (P<0.05, P<0.01); the intra-group comparison of blood glucose level between after modeling and after intervention found significant difference only in group C (P<0.01). The gastrointestinal propulsive rates in group B, group C and group D were significantly different from that in group A (P<0.01 or P<0.05); the gastrointestinal propulsive rates were markedly higher in group C and group D than in group B (P<0.01, P<0.01). The expressions of TMEM16A in group B and group C were decreased compared with group A (P<0.01, P<0.05); the expressions of TMEM16A in group C and group D were increased compared with group B (P<0.01, P<0.05). The fluorescence intensity of Ca2+ was significantly lower in group B than in group A (P<0.01); the fluorescence intensity of Ca2+ was significantly higher in group C and group D than in group B (P<0.01, P<0.05). ICaCC in ICCs in group B was significantly decreased compared with group A; ICaCC in group C and group D were increased compared with group B. Conclusion: EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) can significantly improve gastrointestinal motility in DGP rats by up-regulating the ICaCC in ICCs.

OBJECTIVETo investigate the role of endogenous hydrogen sulfide (H2S) in erectile dysfunction (ED) induced by androgen deficiency.

METHODSWe randomly divided 30 eight-week-old healthy male SD rats into six groups: 2-week control (A), 4-week control (B), 2-week castration (C), 4-week castration (D), 2-week castration + androgen replacement (E), and 4-week castration + androgen replacement (F), those in groups E and F subcutaneously injected with testosterone propionate (TP) at the physiological dose of 3 mg/kg per day after castration, while those in the other groups with isodose oil instead. At 2 and 4 weeks after operation, we determined the level of serum testosterone (T) , intracavernous pressure (ICP) , mean carotid arterial pressure (MAP) of the rats, measured the concentration of H2S in the plasma and corpus cavernosum tissue, and detected the expressions of cystathionine-P3-synthase (CBS) and cystathionine-gamma-lyase (CSE) by immunohistochemistry and Western blot.

RESULTSThe serum T level was significantly lower in group C ([0.63 +/- 0.15] nmol/L) than in A ( [ 16.55 +/- 4.17] nmol/L) and E ( [ 18.99 +/- 4.62] nmol/L) (P <0.05), as well as in group D ([0.70 +/-0.22] nmol/L) than in B ([15.44 +/-5.18] nmol/L) and F ([20.99 +/-6.41] nmol/L) (P <0. 05) , and so were ICP/MAP after 5 and 7 V electrical stimulation of the pelvic ganglia (P <0. 05) , H2 S concentration (P <0.05), and the expressions of CBS and CSE (P <0.05). The expressions of CBS and CSE proteins were also significantly decreased in group C as compared with D (P <0.05).

CONCLUSIONThe reduced expressions of CBS and CSE may inhibit the H2 S signaling pathway, which might be one of the mechanisms underlying androgen deficiency-induced ED in rats.

Androgens ; deficiency ; Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Erectile Dysfunction ; metabolism ; Hydrogen Sulfide ; metabolism ; Male ; Orchiectomy ; Penis ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To study the therapeutic effects and prognosis of advanced pancreatic carcinoma treated with iodine-125 seeds implantation.Methods The records of 98 patients with unresectable advanced pancreatic carcinoma admitted from Mar.2004 to Oct.2008 were analyzed.There were 53 cases treated by supportive treatment,24 cases by palliative operation and 21cases by palliative operation combined with iodine-125 seed implantation.Results Pain partial and complete relief rate in palliative operation combined with iodine-125 seeds implantation radiotherapy group(84.21% and 15.79%,respectively) was better than other two treatment groups(P

0.05),respectively.CONCLUSION:Intravenous drip combined with oral administration of Amoxicillin/Clavulanate Potassium can replace intravenous dip of Amoxicillin/Clavulanate Potassium bid.For those ?-Lactams drugs with short t1/2,the unreasonable intravenous drip of which qd can be replaced by the intravenous drip combined with N-time oral administration or with N-time intramuscular injection.

BACKGROUND: Our previous study showed that the activation of local renin-angiotensin system in heart and vessels contributed to hypertension and cardiovascular remodeling. However, whether oxygen free radical plays an important role in this process is still unclear. OBJECTIVE: To investigate the interventional effects of Ebselen, a kind of anti-oxidative drug, on rats administered by Nw-Nitro-L-arginine methyl easter (L-NAME) (L-NAME), inhibitor of nitric oxide synthase (NOS) for a long term, and probe into the role of oxygen free radicals (OFR) in hyper- tension and cardiovascular remodeling of NO-deficient rats. DESIGN: A randomized grouping and controlled animal trial. SETTING: Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Institute of Cardiology, Nanchang University. MATERIALS: The experiment was completed from January 2002 to March 2003 at the Animal Experimental Lab, Institute of Cardiology, Nanchang University and the Key Molecular Medical Lab of Jiangxi Province. Twenty-four Wistar rats were divided to three groups according to the random number table method: normal control group (n=8), L-NAME group (n=8), L-NAME + Ebselen group (n=8). METHODS: ①Normal control group: The rats could eat and drink routinely, and they were administrated by skim milk ball (net weigh = 4 g) before feed every night. ② L-NAME group: The rats received L-NAME in the dose of 50 mg/kg mixed in one skim milk ball everyday before feed every night. ③ L-NAME + Ebselen group: The rats were admin istered by one skim milk ball (net weigh = 2 g) mixed with L-NAME (50 mg/kg) and one skim milk ball (net weigh = 2 g) mixed with ebselen (30 mg/kg). The systolic blood pressure (SBP) was detected before LNAME was given and at the ends of the 1st, 2nd, 4th,6th and 8th weeks respectively. The rats were killed under anesthesia at the end of the 8th week, the plasma and homogenate of myocardium of apex were taken to detect the biochemical indexes, the other heart tissues were used for the histological detections. MAIN OUTCOME MEASURE: ① Dynamic changes of blood pressure were observed. The levels of NO and malondialdehyde (MDA), activities of angiotensin-converting enzyme (ACE) and superoxide dismutase (SOD) in plasma and myocardium of apex were measured. The production of superoxide anion and the levels of angiotensin Ⅱ type 1 receptor (AT1R) protein expression in myocardium of apex were determined. ③ The pathomor- phological indexes were determined. RESULTS: All the 24 rats were involved in the analysis of results without deletion. ① SBP: At the ends of the 1st, 2nd, 4th 6th and 8th weeks, SBP elevated gradually in the L-NAME group, which were significantly higher than those in the control group at the same time (P ＜ 0.05-0.01). At the end of the 8th week, the SBP was significantly lower in the L- NAME + Ebselen group than in the L-NAME group (P ＜ 0.05). ② Bio chemical indexes in plasma and homogenate of myocardium of apex: The NO level and SOD activity in myocardial tissue were significantly lower in the L-NAME group than in the normal control group (P ＜ 0.05-0.01), but significantly higher in the L-NAME + Ebselen group than in the L- NAME group (P ＜ 0.05-0.01). The production of superoxide anion, ACE activity and level of AT1R expression were all significantly higher in the L-NAME group than in the normal control group (P ＜ 0.05), but signifi- cantly lower in the L-NAME + Ebselen group than in the L-NAME group. ③ Pathomorphological indexes: The ratio of cardiac mass to body mass, thickness of left ventricle and ratio of thickness to lumen diameter of small artery were all significantly higher in the L-NAME group and L- NAME + Ebselen group than in the normal control group (P ＜ 0.05-0.01), and the thickness of left ventricle and ratio of thickness to lumen diameter of small artery were significantly lower in the L-NAME + Ebselen group than in the L-NAME group (P ＜ 0.05) CONCLUSION: Ebselen, an anti-oxidative drug, enable to attenuate the development of hypertension and cardiovascular remodeling in NO-deficient rats. By activating renin-angiotensin system (RAS), OFR may accelerate the formation of hypertension and cardiovascular remodeling, and the increased production of OFR may contribute to the development of cardiovascular remodeling. It is indicated that RAS may play an important role in the development of hypertension and cardiovascular remodeling induced by NO-deficiency