Mammalian target of rapamycin(mTOR)locates at the downstream of phosphatidylinositol 3 kinase(PI3K)-protein kinase B(Akt)cell signal transduction pathway. Studies find that the abnormal activa-tion of this pathway is correlated with the endocrine and drug resistance of anti human epidermal growth factor receptor-2(HER-2)target therapy in breast cancer. The combination with mTOR inhibitors based on the past traditional drugs can block the pathway and reflect a favourable application prospect in preventing the develop-ment of resistance and restoring the initial sensitivity on tumor cells. mTOR inhibitors are expected to be the new hope for the treatment of breast cancer.

The compounds from the root of Rhododendron molle G. Don were isolated, purified by various chromatographic techniques, and their structures were identified according to the physical and chemical features and spectral data. Three compounds were separated from the root of Rhododendron molle G. Don and identified as Rhodojaponin-III, taraxerol, beta-sitosterol for the first time.
Diterpenes/*isolation & purification ; Drugs, Chinese Herbal/chemistry ; Oleanolic Acid/*analogs & derivatives ; Oleanolic Acid/isolation & purification ; Plant Roots/*chemistry ; Rhododendron/*chemistry ; Sitosterols/*isolation & purification

Objective To summarize the nursing methods of Orthofix limb reconstruction system in the treatment of limb long bone defects. Methods Thirty-two patients with long bone defects were collected between January 2012 to January 2015. The patients were all treated with the Orthofix limb reconstruction system and perioperative nursing. Results All the cases were treated by the method for 8 . 5 to 18 . 2 months , averaged 15 . 40 ± 3 . 20 months . The bones extended 4 ~ 21 cm , averaged ( 8 . 06 ± 3 . 06 ) cm . The assessments of bone transport treatment showed 31 cases were excellent and 1 good. Conclusions The limb long bone defects with or without soft tissue defects caused by various causes can be treated by the Orthofix limb reconstruction system. Patients should pay attention to psychological counseling and nutritional support preoperatively. It is important for patients to pay attention to bone transport and functional exercise guidance postoperatively.

Aim To investigate the effect of indirubin derivative PHⅡ-7 and TRAIL on proliferation in breast cancer cell MCF-7 and its MDR counterpart MCF-7/ADR and the mechanism.Methods Growth inhibition rate was examined respectively by MTT assay under treatment with TRAIL or PHⅡ-7 or in combination. Cell apoptosis and ROS production were examined by flow cytometry.The change of TRAIL receptors(DR4/DR5 )in mRNA was analysed by realtime PCR.Re-sults IC50 of PHⅡ-7 on MCF-7 and MCF-7/ADR was (4.49 ±1.55 ),(3.44 ±0.90 )μmol · L-1 respec-tively;MDA-MB-231 was TRAIL sensitive cell line, and apparently TRAIL induced apoptosis in MDA-MB-23 1 .Low concentration of PHⅡ-7 in combination with TRAIL could augment TRAIL-induced cytotoxic effect including apoptosis while TRAIL or PHⅡ-7 treatment alone had limited cytotoxity to those cells.Besides, PHⅡ-7 at this concentration had little toxicity to hu-man peripheral blood mononuclear cells even if in com-bination with TRAIL.PHⅡ-7 generated ROS produc-tion inside MCF-7 and MCF-7/ADR cells and up-regu-lated DR4/DR5 expression concentration dependently. Once upon ROS scavenger NAC involved,the effect of TRAIL receptors up-regualtion by expression was abro-gated.Conclusions PHⅡ-7 at low concentration could improve the sensitivities of breast cancer cell MCF-7 and MCF-7/ADR to TRAIL,the mechanism of which may be the ability of ROS production by PHⅡ-7 help up-regulated TRAIL receptor DR4,DR5 .Our re-search set a solid foundation for PHⅡ-7 in combination with TRAIL in future clinical application.

Objective To compare the therapeutical effect of puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A on cerebral ischemia reperfusion mice. Methods The mice were randomly assigned for sham group, model group, puerarin group, ligustrazine group, ginsenoside Rb1 group, and Hydroxysafflor yellow A group, 24 mice for each group. All the groups were subjected to middle cerebral artery occlusion (MCAO) by 1 h ischemia and 24 h of reperfusion except the sham group. The puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A were administrated by tail vein injection with 3μmol/kg at the onset of 1 h of ischemia. The neurologic deficit score, infarct area calculated by TTC staining, cerebral cortex blood flow monitored by laser doppler flowmetry, NO content measured by chemical colorimetry and western blot were applied to determine the expression for cleaved-caspase-3 and nuclear transcription factor NF-κB for each group. Results Compared with the model group, the infarct area (15.83%± 1.83%, 22.00%± 2.53%, 22.83%± 1.83%, 17.83%± 1.72%vs. 34.67%± 2.66%) in the puerarin group, ligustrazine group, ginsenoside Rb1 group, Hydroxysafflor yellow A group was significantly decreased (P<0.01 or P<0.05);the cerebral cortex blood flow (598.81 ± 9.90 μl/kg?min-1, 614.78 ± 9.20 μl/kg?min-1, 577.83 ± 5.55 μl/kg?min-1, 583.54 ± 7.98 μl/kg?min-1 vs. 548.43 ± 1.97 μl/kg?min-1) significantly increased (P<0.01 or P<0.05);the NO content (17.09 ± 1.18μmol/L, 18.54 ± 0.54μmol/L, 18.17 ± 0.49μmol/L, 15.10 ± 0.73μmol/L vs. 20.63 ± 0.73μmol/L) ignificantly decreased (P<0.01 or P<0.05);the expression of cleaved-caspase-3 (1.02 ± 0.08, 1.12 ± 0.04, 0.87 ± 0.08, 1.07 ± 0.08 vs. 1.30 ± 0.06) and NF-κB p-p65/NF-κB p65 (1.03 ± 0.19, 1.15 ± 0.05, 1.12 ± 0.08, 0.72 ± 0.08 vs. 1.45 ± 0.08) ignificantly decreased (P<0.01 or P<0.05) Conclusions Four Chinese herbal monomers could improve nerve and cerebral dysfunctions and ameliorate ischemia symptoms with varying degrees. The mechanisms were involved with the enhancement of cerebral cortex blood flow and inhibition of cell apoptosis and the activation of inflammatory signaling pathways.

Thirteen of 4-anilinoquinazoline derivatives with imine groups at position 6 of quinazoline ring were synthesized and their antitumor activities were evaluated by MTT assay and Western blotting analysis. Among these compounds, 13a-131 were reported first time. The MTT assay was carried out on three human cancer cell lines (A549, HepG2 and SMMC7721) with EGFR highly expressed. Among the tested compounds, 13i and 13j exhibited notable inhibition potency and their IC50 values on three cell lines were equivalent to or less than those of gefitinib. Compound 14, without imine group substituted, displayed excellent inhibitor potency only on A549 cell line. Compounds 14 and 13j were chosen to perform Western blotting analysis on A549. The results showed that both of the compounds could inhibit the expression level of phosphorylated EGFR remarkably. It was concluded that the inhibitor potency of compound 14 was almost equivalent to that of gefitinib and the inhibitor potency of 13j was better than that of gefitinib.

Objective To observe changes of the pancreas after limb ischemia reperfusion, and the protective effect of taurine (Tau) postconditioning. Methods Twenty-four male SD rats were randomly divided into control group (Control), limb ischemia reperfusion (LIR) group, and taurine postconditioning (Tau) group (n=8 for each group). Plasma contents of xanthine oxidase (XOD), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), pancreatic amylase (AMS), pancreatic lipase (LPS) and trypsin were detected in three groups. Morphological changes of the pancreas were observed using optical microscopy. The expressions of anti-C/enhancer-binding protein homologous protein (CHOP) in pancreas were analyzed by immunohistochemistry assay. TUNEL staining was performed to estimate the apoptosis of pancre-atic cells. Results Compared with the control group and Tau group, plasma contents of MDA, XOD, ROS, AMS, LPS, and trypsin were significantly increased in LIR group, but the level of SOD was significantly lower in LIR group ( P<0.05). HE staining showed that acinar structure was disrupted , pancreatic lobule gap widened, stromal vascular dilatation and conges-tion were observed in LIR group. The perivascular infiltration of inflammatory cells appeared, islet cells were damaged with irregular islet. The immunohistochemical analysis showed the increased expression of CHOP in pancreas in LIR group than that of Tau group. And the pancreatic apoptosis was enhanced in LIR group detected by TUNEL staining. Conclusion Tau-rine postconditioning can ameliorate pancreatic injury following limb ischemia reperfusion, which may be related to the inhi-bition of oxidative stress, down-regulation of CHOP expression, thereby reducing endoplasmic reticulum stress-induced apoptosis.

Objective To evaluate the effect of lappaconitine on renal ischemia-reperfusion (I/R) injury in mice.Methods Thirty-six male Wistar rats,weighing 180-220 g,were randomly divided into 3 groups (n=12 each) using a random number table:sham operation group (group S),group I/R and lappaconitine group (group LA).Renal I/R was induced by occlusion of the left renal pedicle for 45 min with atraumatic microclips followed by reperfusion,and the right kidney was removed after atraumatic microclips were released.At 30 min before reperfusion,lappaconitine 4 mg/kg was injected intraperitoneally in group LA,and normal saline 2 ml was given in S and I/R groups.In group S,the left renal pedicle was only isolated.At 5 and 24 h of reperfusion,blood samples were taken from the inferior vena cava for determination of serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations,and kidney specimens were obtained for histopathologic examination (with light microscope) and for determination of the expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) in renal tissues (by immunohistochemistry).Results Compared with group S,the serum Cr and BUN concentrations were significantly increased,and the expression of COX-2 and MMP-2 in renal tissues was up-regulated at 5 and 24 h of reperfusion in I/R and LA groups.Compared with group I/R,the serum Cr and BUN concentrations were significantly decreased,the expression of COX-2 and MMP-2 in renal tissues was down-regulated at 5 and 24 h of reperfusion and histopathologic changes were reduced in group LA.Conclusion Lappaconitine can attenuate renal I/R injury through inhibiting the expression of COX-2 and MMP-2 in rats.

Objectiv e To investigate the correlation between ( CAG) n repeat polymorphism of androgen receptor(AR)geneandmalebreastcancer.Methods 40casesofmalebreastcancerand40controlswerecol-lected.DNA was extracted from peripheral blood and the AR gene CAG coding exon sequences for PCR amplifica -tion,sequencing and calculated the number of CAG repeats frquency .χ2 test and Logistic regression analysis were used assess the AR gene CAG repeat length frequency affect the number of male breast cancer risk .Results There was statistically significant difference in male breast cancer cases and controls the number of CAG repeat length frequency.Man for whom the(CAG)n≥22 repeat sequence had 3.52 times risk of male breast compared (CAG)n≤22(OR=3.52,P=0.036).Conclusion AR gene CAG repeat length is a predictor of the frequency of male breast cancer risk .Longer CAG repeats can increase the risk of male breast cancer .

Objective To evaluate the effects of sinomenine on the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) during renal ischemia-reperfusion (I/ R) in rats.Methods Fifty-four male Wistar rats, weighing 180-220 g, were randomly divided into 3 groups (n=18 each) using a random number table: sham operation group (group S) , group I/R and sinomenine group (group SIN).Renal I/R was induced by clamping the left renal pedicle for 45 min followed by reperfusion in I/R and SIN groups.In group S, the bilateral renal pedicels were only exposed.Sinomenine 60 mg/kg was intraperitoneally injected at 30 min before reperfusion in group SIN, while the equal volume of normal saline was given in group S and group I/R.At 6, 12 and 24 h (T1-3) of reperfusion, 6 rats from each group were chosen, and blood samples were drawn from the hearts for determination of the serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations.The animals were then sacrificed, and the left kidney was removed and embedded into a paraffin block for determination of the expression of HIF-1α and VEGF in the renal tissues (by immuno-histochemistry).Results Compared with group S, the serum Cr and BUN concentrations were significantly increased at T1-3 , and the expression of HIF-1α was significantly up-regulated at T2,3 in group I/R and group SIN, and the expression of VEGF was significantly upregulated at T2,3in group I/R, and at T1-3 in group SIN.Compared with group I/R, the serum Cr concentration at T1-3 and serum BUN concentration at T2,3 were significantly decreased and the expression of HIF-1α at T2,3and VEGF at T1-3was significantly up-regulated in group SIN.Conclusion The mechanism by which sinomenine attenuates renal I/R injury is related to up-regulation of the expression of HIF-1α and VEGF in the renal tissues of rats.