Ras/Raf/MEK/ERK singal transduction plays an important role in cell proliferation, differentiation, apoptosis, metastasis and metabolism. This investigation focused on this signal pathway and chose farnesyl transferase (FTase) as the main target and Raf-1 kinase as the second target. A lot of compounds were selected to construct the pharmacophore models of farnesyl transferase inhibitors (FTIs) and Raf-1 kinase inhibitors by using computer-aided drug design (CADD). The pharmacophore of FTIs is constituted by a hydrogen bonding acceptor, an aromatic ring, a positive ionizable and two hydrophobic regions; the pharmacophore of Raf-1 kinase is constituted by a hydrogen donor, a hydrogen acceptor, a hydrophobic regions and an aromatic ring. There are some similarities between the two pharmacophores. After analysis of the constructions of these two pharmacophores, some new aminomethylbenzoic acid derivatives with good forecasting activity against both of FTase and Raf-1 kinase were designed with these new pharmacophore models.

Objective To investigate and evaluate the clinical effect of the application of medical adhesive in limited septoplasty by endoscope.Methods 57 patients were selected to undergo operation of limited septoplasty by endoscope.The patients were divided into packing group and bonding group.The packing group had 29 patients,whose nasal cavity was packed with vaseline gauze.While the bonding group had 28 patients,their nasal septum mucosa was adhesive fixed by medical adhesive,and the nasal cavity without packing.The indexes included the cardinal symptoms(nasal pain and headach,sleep status),signs (seepage amount of bleeding,mucosal edema),degree of discomfort in nasal cavity processing after operation(pain and bleeding) and length of stay were compared between the two groups.Results The above indexes in the bonding group were apparently lightened than the packing group and the length of stay was shortened.The differences were statistically significant (all P ＜ 0.05).Conclusion In operation of limited septoplasty by endoscope,the using of medical adhesive replacing nasalpacking could reduce the trauma on patients by operation and lighten the pain.The curative effect is satisfactory and it has excellent clinical application value.

Objective:To investigate the influence of miR-7 knock down on the development of CD 4+SP cells in the thymus in mice,and preliminary explore its possible mechanism.Methods:The changes of volume ,weight and total cell counts of thymus in miR-7 knock down (miR-7KD) mice were observed compared with Wild-type(WT)mice;the pathological changes of thymus were observed by HE staining.FACS analysis was performed on the proportion ,as well as the expression level of CD44 and CD62L,of thymus CD4+single positive (SP) cells.Meanwhile,the proliferation percentage of CD4+SP cells was measured by Ki-67 staining.The apoptosis percentage of CD4+SP cells was analyzed by FACS.The changes on the transduction of ERK 1/2 pathways were determined by Western blot.Results:Compared with WT mice ,the size,weight and total cell number of thymus were marked reduced in miR-7KD mice( P<0.05 );moreover ,pathological change also was presented.The proportion and total cell number of thymus CD 4+SP cells were marked decreased ( P<0.05 ).Furthermore ,the expression level of CD 44 and proliferation percentage ,as well as apoptosis percentage ,of CD4+SP cells were obviously increased (P<0.05),however,the expression level of CD62L of CD4+SP cells were decreased (P<0.05). Finally,the level of total ERK1/2 and phosphor-ERK1/2 was decreased obviously ( P<0.05 ).Conclusion: miR-7 knock down can affect the development of CD 4+SP cells in the thymus , which might be closely related to the cell activation state and altered the transduction of ERK1/2 pathways.

Objective:To detect the change of proportions of αβT lymphocytes in mesenteric lymph nodes of miR-7 knockdown (miR-7KD)mice,and preliminarily explore its importance.Methods: The volume,weight index and total cells number of mesenteric lymph node in miR-7KD mice were measured.The pathologic morphology change of mesenteric lymph nodes was observed by HE stai -ning.And the changes on proportion of αβT lymphocytes in mesenteric lymph nodes of miR-7KD mice were analyzed by Flow cytometry.Results:Compared with those of WT (wild type) mice,the volume,weight index,and the total cells number of mesenteric lymph node were significantly increased ( P<0.05 ).Moreover ,the pathologic morphology was significantly changed.The proportion and numbers of T lymphocyte were significantly increased;however,the proportion of B lymphocyte were significantly decreased (P<0.05). Notably,the proportion and number of CD4+T cells and CD8+T cells were significantly increased (P<0.05).Meanwhile,CD62L+T cell proportion were vigorously reduced and CD 69+T cell and IFN-γ+T cell proportion were notably up-regulated,which belong to CD4+and CD8+T cell(P<0.05).Conclusion:There was significant influence in the proportion of αβT lymphocytes in mesenteric lymph nodes of miR-7KD mice,suggesting that miR-7 might play an important role in the composition and function of lymphocytes in mesenteric lymph nodes.

Objective To observe the effect of pre-intervention with electroacupuncture at Neiguan (PC 6) plusα2-adrenoceptor (α2AR) agonist on peri-operative heart rate variability (HRV).Method A total of 120 patients going to receive lower limb orthopedic surgery were randomized into four groups by using the random number table, namely a control group (group A), an electroacupuncture group (group C), anα2AR agonist group (group D) and an electroacupuncture plus medication group (group N), 30 cases in each group. The indicators of heart rate variability (HRV), including the standard deviation of normal-to-normal (N-N) intervals (SDNN), standard deviation of the average of N-N intervals (SDANN), root mean square successive differences (rMSSD), percentage of adjacent N-N intervals>50 ms apart (pNN50), low-frequency power (LF), high-frequency power (HF), LF/HF and total power (TP) were recorded 1 d prior and 1 d after the operation; meanwhile, the mean arterial pressure (MAP) and heart rate (HR) were recorded before incubation (T0), right after incubation (T1), 5 min after incubation (T2), right afterextubation (T3), 5 min after extubation (T4), 60 min after extubation (T5), and 180 after extubation (T6).Result In group N, the HR and MAP at the other time points were insignificantly different from those at T0 (P>0.05); in group A, the HR and MAP at T1-T6 were significantly different from those at T0 (P<0.05); in group C and D, the HR and MAP at T1-T4 were significantly different from those at T0 (P<0.05); the HR and MAP in group N were significantly lower than those in group A at T1-T6 (P<0.05) and were significantly lower than those in group C and D at T1-T4 (P<0.05); the HR and MAP in group C and D were significantly lower than those in group A at T5 and T6 (P<0.05). In group A, the LF, HF, LF/HF and TP 1 d after the operation were significantly increased compared to those 1 d prior to the operation (P<0.05); in group A and D, the SDNN, SDANN, rMSSD, and pNN501 d after the operation were significantly lower than those 1 d prior to the operation (P<0.05); the LF, HF, LF/HF, and TP in group C, D and N were significantly lower than those in group A 1 d after the operation (P<0.05); the SDNN, SDANN, rMSSD, and pNN50 in group C and N were significantly higher than those in group A and D 1 d after the operation (P<0.05). Conclusion Pre-intervention electroacupuncture plusα2AR agonist can improve the balance of cardiac sympathetic and vagus nerves, and better maintain the peri-operative hemodynamic stability.

Objective To investigate the relationship of preoperative level of serum anterior gradient 2 (AGR2)with clinicopathological features and prognosis of patients with prostate cancer. Methods The serum levels of AGR2 were detected by ELISA in 72 patients with prostate cancer, 30 patients with benign prostatic hyperplasia (BPH) and 20 healthy controls. The receiver operating characteristic (ROC) curve was drawn to determine the optimal cut-off value of clinical diagnosis, and to analyze the diagnostic value of serum AGR2 in prostate cancer. Kaplan-Meier method was used to plot the survival curve. Log-rank test was used to analyze the difference of survival time between the two groups. The effect of AGR2 on the prognosis of prostate cancer patients was analyzed by Cox regression. Results The level of serum AGR2 in prostate cancer group was obviously higher than those in BPH group and health control group (t=4.441, t=5.285, both P<0.01).Serum AGR2 level was correlated with Gleason score,tumor stage, lymph node metastasis and preoperative PSA level (F=11.343, F=9.613, t=3.882, t=7.514, all P<0.01). The area under the ROC curve(AUC) of AGR2 was 0.803(95%CI 0.726-0.880,P=0.000), when the cut-off value was 17.25 ng/ml, the sensitivity rate was 63.9%, specificity rate was 80.0%. Kaplan-Meier survival analysis showed that the survival rate in low AGR2 expression group was significantly higher than that in high AGR2 expression group (χ 2=5.565, P=0.018). Cox regression analysis showed that AGR2 was an independent risk factor for prostate cancer patients (HR=5.412, 95%CI 1.143-25.624, P=0.033). Conclusions The elevated level of serum AGR2 is related with tumor progression in prostate cancer. It may be a potential marker for predicting prognosis of patients with prostate cancer.

Objective To explore the inhibiting effect of superoxide dismutase (SOD) on the growth of hepatocellular cancer cell line HepG2. Methods By gene transfer technique, hepatocellular cancer cells (HepG2) were transfected with a retroviral vector containing human CuZnSOD cDNA. The elevated SOD gene expression of the transfected cells was compared with the parental and neo control cells. Results Compared to the control cells, cancer cells transfected with SOD gene showed an inhibited cell growth, a reduced number of cells in S phase and decreased clone forming ability in soft agar, as well as a smaller tumor size formed in nude mice.Conclusion The overexpression of CuZnSOD gene could, to certain extent, suppress the cell growth of hepatocellular cancer cell line HepG2.

Objective To study the effects of the p16 gene on tumor cell growth inhibition and cell cycle arrest. Methods The recombinant retroviral vector pLp16SN was constructed by cloning the human p16 cDNA into the retroviral vector pLXSN. Retroviruses with or without the p16 gene were obtained by transfecting pLp16SN and pLXSN vectors into PA317 cells. Bcap-37 human breast cancer cells were infected with these retroviruses followed by selection with G418. The expression of p16 was detected by Northern and Westem blots. Cell biological characteristics, including cell growth rate, cell cycle and tumorigenesis in nude mice were assessed.Results Both mRNA and protein expression of p16 in Bcap-37 cells transfected with retroviral vector containing the p16 gene were much higher than that in Bcap-37 cells transfected with empty vector or parental Bcap-37 cells. Cell overexpressing the p16 gene exhibited a slower rate of growth, a higher percentage of cells in the G1 phase, and smaller tumors in nude mice, compared with parental Bcap-37 cells and cells transfected with empty vector.Conclusion Overexpression of the p16 gene could suppress the growth of Bcap-37 breast cancer cells by arresting the cell cvcle at the G1 to S-phase.

Inflammatory bowel disease (IBD) is a group of chronic non-specific intestinal inflammatory diseases with unknown etiology. Irritable bowel syndrome (IBS)-like symptoms may occur in IBD in remission, which has a negative impact on the quality of life and prognosis of the disease. This article reviewed the progress of research on epidemiology, pathological mechanism, diagnosis and treatment of IBD in remission overlapping IBS-like symptoms both at home and abroad, in order to provide references for the diagnosis and treatment of IBD in remission and the management of chronic disease.

The blood-brain barrier (BBB) constitutes a major obstacle to effective delivery of drugs to the brain. Recent technological advances have led to improvements in brain-targeted drug delivery. In this review, we summarize existing technologies for efficient drug delivery across the BBB. We discuss the mecha-nisms of current BBB-based drug delivery strategies and introduce prospects for application in brain-targeted delivery of traditional Chinese medicine. We highlight the use of physical techniques for brain-targeted drug delivery, including electroporation, ultrasound, magnetophoresis, microneedles, microwaves, and laser. The characteristics of these techniques and relevant studies employing these approaches are discussed. In general, microneedles, lasers, ultrasound, electroporation, magnetophoresis, and microwaves are effective for drug delivery across the BBB. Notably, the synergistic effects of multiple approaches are superior to the additive effects of each technique in isolation. Our review provides guidance for the practical application of brain-targeted drug delivery techniques in an efficient and safe manner.