In this paper, we investigate the boundedness character, the global attractivity and the periodic nature of the system of rational difference equations: xn+1 = p+yn-k/xn, yn+1 = q+xn-k/yn, n=0,1,2⋯, where p>0, q>0, k∈ {1,2,⋯} and the initial values xi, yi∈(0, ∞), i=-k, -k+1, ⋯,0. Some new results are obtained.

In this paper, we investigate the boundedness character, the global attractivity and the periodic nature of the system of rational difference equations: xn+1 = p+yn-k/xn, yn+1 = q+xn-k/yn, n=0,1,2⋯, where p>0, q>0, k∈ {1,2,⋯} and the initial values xi, yi∈(0, ∞), i=-k, -k+1, ⋯,0. Some new results are obtained.

OBJECTIVE: To investigate the protective effect of fenofibrate (Fen) on acute focal cerebral ischemia reperfusion injury in mice and its mechanisms. METHODS: Cerebral ischemia was induced by middle cerebral artery occlusion in mice for 90min and then reperfusion. Fen (10, 80 mg · kg-1) was intragastrically administered at the same time of reperfusion and 2 h after reperfusion respectively. The neurological deficit score, infarct volume and brain edema degree were determined 24 h after reperfusion. At the same time the expression of PPARα mRNA in brain tissue was measured by real-time RT-PCR. The contents of maiondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the brain tissue were measured by biochemical assay. The disruption of blood-brain barrier(BBB) was evaluated by the extravasations of Evans Blue (EB). MK886, an antagonist of PPARα receptor, was used to investigate the involvement of PPARα in the protective effect of Fen. RESULETS: Fen (80 mg · kg-1) ameliorated neurological function, reduced infarct volume, attenuated brain edema degree, decreased the extravasations of EB, increased the expression of PPARα mRNA, and attenuated the lipid peroxidation in brain tissues. MK886 abolished the protective effect of Fen. CONCLUSION: Fen has protective effect against acute focal cerebral ischemia reperfusion injury in mice by increasing the expression of PPARα mRNA and reducing lipid peroxidation in brain tissue.

Personalized targeted therapy in addition to standard chemotherapy has become a hot topic in the treatment of metastatic colorectal cancer (mCRC). KRAS gene mutation has been considered as a predictor for poor response to anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR) therapy in patients with mCRC. The percentage of KRAS mutation is 35%-45% in patients with mCRC, and these patients have poor response to anti-EGFR; while only 50% of patients with wild-type KRAS respond to anti-EGFR, which suggests that the activation and variation of other molecules in the downstream of EGFR signaling pathway can influence the therapeutic effects. The two major EGFR-dependent signaling pathways - RAS-RAF-MAPK and PI3K-PTEN-AKT may be involved in poor response to anti-EGFR in the treatment of mCRC. In addition, the increased EGFR gene copy number (GCN) is associated with the efficacy of anti-EGFR therapy, but not associated with the expression level of EGFR protein which has no correlation with the efficacy of anti-EGFR therapy. Additional detection of mutations in BRAF and PIK3CA genes as well as deletion of PTEN gene in wild-type KRAS patients with mCRC may be helpful in further selection of patients with anti-EGFR resistance. This paper reviews recent progress on molecular markers associated with treatment outcome and prognosis predictions in the treatment of mCRC, in order to guide individualized molecular targeted therapy for mCRC. Copyright© 2011 by TUMOR.

Objective: To investigate the interaction between tanshinone IIA (TS IIA) and cholesteryl ester transfer protein (CETP), and to explore the ways of impact on CETP. Methods: The various structures of TS IIA and CETP were built based on the crystal structure and then performed molecular dynamics (MD). The simulation software is Gromacs 4.0 with force field of Gromos 96 53a6. The temperature is 300 K and the simulation time is 20 ns. All trajectories were recorded to analyze the changes of overall shape and local structures of CETP, and the interaction energy between TS IIA and CETP. Results: When the phosphatidyl choline zones of CETP were full, the structure was rigid. When only the cavity was loaded, CETP was easy to change. The out area of two side, phosphatidyl choline area and cavity change greatly corresponded to the frame changes of CETP. Stronger interaction between TS IIA and CETP occured in the two phosphatidyl choline area and the left side of cavity. Conclusion: CETP is a carrier protein with easily changed structure which changes according to the differences in the number and structures of loading ligands. TS IIA might affect the morphology of the CETP and then inhibit its transportation ability under the help of phosphatidyl choline or cholesterol ester.

Aim To explore the protective mechanisms of Chaiqinchengqi decoction (CQCQD) on liver injury during severe acute pancreatitis ( SAP) based on TLR4/NF-kB p65 pathway. Methods Thirty-six KM mice were randomly divided into control group (Control) , SAP and SAP + CQCQD (treatment group) (n = 12). The mice in SAP group were injected with 20% L-arginine intraperitoneal^ (3.3 g • kg"1, 2 times, 1 h interval). The mice in SAP + CQCQD group were intragastrically administered with Chaiqinchengqi decoction (19 g • kg-1 • d"1) following induction of SAP. Histopathologic^ changes of pancreas and liver were observed 72 hours after model establishment. The endotoxin in serum was tested, and the TLR4 and p-NF-kb p65 expression, as well as some inflammatory cytokines in liver was detected. Re-suits Compared to control group, the pathological damages of the pancreas and liver in SAP group were aggravated, serum endotoxin increased, the expression of TLR4 and p-NF-kB p65 in liver increased, and IL-6, TNF-a and MIP-1 a mRNA in liver were significantly elevated. Compared to SAP group, the intervention of CQCQD partially relieved the pathological damages of the pancreas and liver, reduced the endotoxin in serum , and decreased the expression of TLR4 and p-NF-kB p65, as well as IL-6, TNF-a and MIP-1 a mRNA in the liver. Conclusion CQCQD appears to protect liver injury during SAP via inhibiting TLR4/NF-kB p65 activation, then decreasing cytokines and chemo-kines.

Objective To investigate the changes of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) and angiotensin converting enzyme (ACE)/angiotensin II(Ang II)/angiotensin II type 1 receptor (AT1R) axis and their impact on the development and progression of silicotic fibrosis. MethodsSixty male Wistar rats were randomly divided into 6 groups (n=10). The rats inhaled dust for 0, 2, 4, 8, 12, and 16 weeks (w) respectively to reproduce silicosis model. HE staining was performed to observe the pathological changes of the lung tissue. The expression of α smooth muscle actin (α-SMA), collagen I (Col I), fibronectin (Fn), ACE and AT1R were measured by Western blotting. The levels of Ac-SDKP and Ang II in lung tissue were detected by ELISA. ResultsMacrophage infiltration and widened alveolar wall were observed by HE staining in the silicosis 2-w group. Isolated cell lesions which composed of macrophages were seen in silicosis 4-w group. The alveolar wall widened obviously and the number of silicotic nodules increased at 8w and 12w. The fusion of silicotic lesions, interstitial fibrosis and fibrous lesions were observed at 16w. Compared with control group, the expressions of α-SMA, Col I and Fn protein in silicosis 4-, 8-, 12-, and 16-w group increased gradually. In silicosis 2-, 4-, 8-, 12-, 16-w group, the expressions of ACE, Ang II and AT1R gradually increased compared to the control. The level of Ac-SDKP in the lung tissue of silicosis 2-w group was significantly higher than that in control group, and then decreased gradually, and significantly lower in the silicosis 12- and 16-w group than the control (P<0.05). ConclusionAlong with the development and progression of silicosis, ACE, Ang II, and AT1R expressions gradually increase in local lung tissue, while the expression of Ac-SDKP gradually decreases. Ac-SDKP and Ang II signal would participate the silicotic fibrosis process in rats.

Objective To establish a paclitaxel-resistant BNX mouse model of human lung carcinoma, so as to provide evidences for studying chemoresistant mechanism and for screening of the reversal drugs in vivo. Methods The resistant model was produced by repeating a crossover subcutaneous injection of human lung cancer A549-Taxol cells and transplantation of tumor fragment into immune deficiency mice, so as to increase the tumor forming rate of A549-Taxol cells and shorten the tumor forming time. The expressions of GST-k, P-gpl70 and MMP-7 were examined by immunohistochemical staining. The chemosensitivities of tumor cells to Taxol were tested and IC50 was measured by MTT. Results Tumor niduses were observed subcutaneously in SCID mice 4 months after injection of A549-Taxol cells, and then the tumor fragment or the tumor cells suspension were injected to SCID mice again. After 3 times of crossover injection, the tumor cells grew faster and tumor niduses were formed 2 months after injection. The same procedure was done in BNX mice. Finally, we achieved a successful rate of 80% in tumor implantation in BNX mice; the tumor niduses could be formed in 3 weeks. P-gpl70, GST-* and MMP-7 expression was higher in the experiment group than that in the A549 control group. IC50 value of paclitaxel for A549-Taxol cells was 520 folds that of A549 cells. Conclusion We have successfully established paclitaxel-resistant lung carcinoma model in mice, which provides a new platform for further study on chemoresistant reversal strategy and individualized clinical treatment.

OBJECTIVE: To review mechanism research progress of ganoderan antitumor. METHODS: At the foundation of research literature of domestic and abroad, the different kinds of antitumor mechanism of ganoderan were summaried. RESULTS AND CONCLUSION: Now, polysaccharides become a research hotspot as antitumor immunomodulator. The study reviewed mechanism of ganoderan antitumor at different fields; elevating the immune function of host, inhibiting tumor cell proliferation and metastasis, anti-oxidant, clearing oxygen radicals, increasing the expression of tumor MHC and costimulatory molecules, inducing tumor cell differentiation. The study also observed the existent problem of ganoderan research.

OBJECTIVE: To explore the proliferation inhibition and apoptosis induction effect of dextran-magnetic layered double hydroxide-fluorouracil (DMF) drug delivery system on colon cancer cell SW480 cultivated in vitro. METHODS: MTT experiment was used to detect the cell proliferation inhibition rates of DET-MLDH-FU, MLDH-FU and MLDH supra-molecules at various concentrations. Light microscopy and Giemsa dyeing methods were applied for characterizing the shape change of the apoptotic cells. Flow cytometric analysis was employed to test the apoptosis rates of SW480 cells treated with different drugs for 24 h. DNA ladder method was used to analyze nuclei breakup of the apoptosis cells. RESULTS: The IC50 of MLDH, MLDH-FU and DMF three-level supra-molecules for SW480 cells were 44.83(25.74, 48.78), 15.16(13.78, 16.66) and 13.33 (11.03, 15.13) μg · mL-1, respectively. The proliferation of colon cancer cells SW480 was obviously restrained after being treated with 5-Fu and equivalent MLDH, MLDH-FU and DMF of different concentrations for 24, 48 and 72 h, respectively. The result revealed that the inhibition rates increased in the sequence of MLDH