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.

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.

Objective To investigate the value of Stroop test, a neuropsychological test, in the diagnosis of minimal hepatic encephalopathy (MHE). Methods A total of 96 patients with liver cirrhosis who were hospitalized in Department of Infectious Diseases, The First Affiliated Hospital of Bengbu Medical College, from August 2020 to March 2021 were enrolled, and the number connection test-A (NCT-A), digit symbol test (DST), animal naming test (ANT), and Stroop test were performed for all patients. Test results were recorded and related clinical data were collected. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was used to investigate the value of Stroop test in the diagnosis of MHE, and the Pearson correlation coefficient was used to analyze the correlation of the results of Stroop test with those of NCT-A, DST, and ANT. Results For the 96 patients with liver cirrhosis, the prevalence rate of MHE was 30.21% (29/96). The Off+On time of Stroop test had a cut-off value of 212.49 s in the diagnosis of MHE, with an area under the ROC curve of 0.845, a sensitivity of 93.10%, and a specificity of 64.20%. The Pearson correlation analysis showed that the On+Off time and On time of Stroop test were moderately correlated with NCT-A( r =0.580 and 0.590, both P < 0.01), the Off time of Stroop test was strongly correlated with NCT-A( r =0.620, P < 0.01), and the On+Off time, On time, and Off time of Stroop test were strongly correlated with DST( r =-0.650, -0.650, and -0.630, all P < 0.01). Conclusion In the diagnosis of MHE, Stroop test is a highly sensitive method with easy-to-read results and a high diagnostic value and does not require professional equipment.

Sarcopenia is one of the manifestations of malnutrition in patients with liver cirrhosis. Most studies have shown that sarcopenia is associated with overt hepatic encephalopathy (OHE), leading to an increased risk of events such as reduced quality of life, poor clinical prognosis, and even death in patients with liver cirrhosis, but there are few studies on the association between sarcopenia and minimal hepatic encephalopathy (MHE). This article reviews the research advances in sarcopenia and hepatic encephalopathy to provide a reliable basis for clinical treatment, and it is pointed out that the nutritional status of patients can be improved to prevent MHE and even reduce the onset of OHE, thereby improving patient prognosis, increasing quality of life, and reducing the risk of death.

Background and Objectives: p21, an important member of the Cip/Kip family, is involved in inhibitory effects of RUNX1b overexpression during the early stage of human hematopoiesis. Methods: and Results: We established a human embryonic stem cell (hESC) line with inducible expression of p21 (p21/hESCs). Overexpression of p21 did not influence either mesoderm induction or emergence of CD34＋ cells, but it significantly decreased the production of CD43＋ cells and changed the expression profile of hematopoiesis-related factors, leading to the negative effects of p21 on hematopoiesis. Conclusions In RUNX1b/hESC co-cultures when RUNX1b was induced from D0, perturbation of the cell cycle caused by upregulation of p21 probably prevented the appearance of CD43＋ cells, but not CD34＋ cells. The mechanisms via which CD34＋ cells are blocked by RUNX1b overexpression remain to be elucidated.