Rectal cancer is a common type of malignant tumor, with increasing incidence over the previous years. Total mesorec-tal excision is the most important treatment for rectal cancer. Advanced rectal cancer presents high local recurrence rate and low sphinc-ter preservation rate. For locally advanced rectal cancer, neoadjuvant chemoradiotherapy is the optimal management strategy. In this re-gard, clinicians have focused on investigating the clinical effects of rectal cancer after neoadjuvant chemoradiotherapy. Prediction and evaluation of rectal cancer after neoadjuvant therapy can be used to determine further necessary treatments, effect on quality of life, and survival time of patients.

Objective To observe the efifcacy of rosuvastatin in patients with unstable angina and its impact on the levels of lipids, high sensitive C-reactive protein (hs-CRP), homocysteine(Hcy) and troponin I (cTnI). Method 384 patients with unstable angina, from January 2010 to December 2012, were randomly divided into observation group and control group, each group had 192 cases, the control group received simvastatin, the observation group were gave rosuvastatin. The efficacy, and the levels of lipids, hs-CRP, Hcy and cTnI were observed after treatment. Results The total effective rate was 92.19%in observation group which was signiifcantly better than 81.25%in control group (χ2=9.044, P<0.01). Before treatment, the levels of TG , TC, LDL-C, HDL-C, Hcy, hs-CRP and cTnI showed no signiifcant difference, after treatment the levels of TG , TC and LDL-C, Hcy, hs-CRP and cTnI were signiifcantly lower than those before treatment (P<0.01), while, the levels of HDL-C signiifcantly increased than those before treatment (P<0.01), the reducing or increasing levels in observation group were more signiifcant compared with the control group (P<0.01). Conclusion Rosuvastatin treatment in unstable angina not only can reduce plasma lipid, but also reduce their inflammation, and stabilize the arterial plaque for unstable angina, it play an important role in development and prognosis.

Intraperitoneal chemotherapy is a useful treatment of advanced gastric cancer.Following intraperitoneal chemotherapy, the concentration of drugs in the peritoneum and in the portal vein was high, lasting and sustained.Early post-operation chemotherapy showed better results.This article will summarize the newest research progress of intraperitoneal chemotherapy in the treatment of advanced gastric cancer.

Objective To observe pain behavior and the expression of Fos in the related brain re? gions,including Anterior Cingulate Cortex ( ACC) ,Periaqueductal Gray ( PAG) ,Rostral ventromedial nucle?us ( RVM) in chronic constrictive injury ( CCI) rats and to explore whether ACC modulate spinal nociceptive transmission through endogenous descending facilitatory system. Methods A total of 48 male SD rats were randomly divided into six groups:Naive group,Sham group ( just separated the left sciatic nerves without liga?tion) ,CCI group ( the left sciatic nerve was ligated) ,CCI+P group ( on the 14 th day after surgery,intraper?itoneal injection of 10 mg/kg paroxetine 45 min before behavior test) ,ACC?Sham group ( bilateral microin?jection of 0.9% NaCl in ACC,1μl/each side) and ACC?AP5 group ( bilateral microinjection of AP5 25 mM in ACC,1μl/each side on the 13th day after surgery) . On the 14th day after light?dark transition test,forced swimming test,paw?withdrawal mechanical threshold( PWMT) and paw?withdrawal thermal patency( PWTL) were performed,the rats were terminally anesthetized and ACC,PAG,RVM and the spinal cord was rapidly removed,and then the expression of c?fos was measured by immunohistochemistry. Results ( 1) Rats in CCI group demonstrated nociceptive hypersensitivity and depressive?like behaviors compared with Naive rats, while rats in CCI+P group and in ACC?AP5 group showed less nociceptive hypersensitivity and less depres?sive?like behaviors compared with CCI group. (2)Compared with Naive group,the number of c?fos positive neurons in the bilateral ACC (left,surgery side,4920.6±1053.7;right,2059.3±409.1),VIPAG (9074.8± 2320.3),RVM (6195.4±895.0) and bilateral spinal cord (left,15148.8±3080.2;right,6400.2±1558.4) was significantly enhanced in CCI group, especially in the left side. In contrast, the amount of fos labeled neurons declined in the bilateral ACC (left,2776.4±820.1;right,1120.5±141.4),VIPAG (4002.2± 1171.8),RVM (2938.9±910.3) and bilateral spinal cord (left,8742.0±1131.0;right,3933.1±858.9) in CCI+P group and also declined in the bilateral ACC (left,3623.1±667.4;right,696.5±164.8),VIPAG (5668.8±1403.3),RVM (3972.3±851.7) and bilateral spinal cord (left,10675.4±1725.3;right,3818.3± 1085.1) in ACC?AP5 group. Conclusion Endogenous descending facilitatory system may contribute to ACC modulating spinal nociceptive transmission.

ive] To observe the effects of Shengjiang Capsule (SC) on gastric evacuation and to study its mechanism. [Methods] Eight-week-old SD rats were randomly allocated to five groups. Group A served as normal control, and Group B were treated with high dosage of SC, Group C with low dosage of SC, Group D with Zhike Baizhu Decotion and Group E with cisapride. After ten days of treatment, gas tric evacuation of rats was detected by isotope tracing method, erythrocyte-acetycholinesterase activity by micro-hydroxylamine method and plasma motilin (Mot) and somatostatin (SS) levels by radioimmunoas-say. [Results] Thirty-minute gastric evacuation rate was (51.44?.38)%, (40.82 + 7.24)% and (40.22?.16)% in Group B, Group C and Group D respectively, which was higher than that in Group A [ (33.18?.32)%]. Erythrocyte-acetycholinesterase activity, Mot and SS levels were (0.856?.128) umol/h, (124.26?5.94) ng/L and (39.42?.96) ng/L, and (0.726?.164 ) umol/h, (119.86 ?9.38) ng/L and (38.33 ?.64) ng/L in Group B and Group C respectively, which were higher than those in Group A [ (0.576 ?.150)/umol/h, (91.28 + 26.84) ng/L and (28.22 ?7.68)ng/L]. [Conclusion] SC can promote gastric evacuation, and its mechanism may be re lated to the increase of the cholinergic nerve function and plasma Mot and SS levels.

Through phage display, we tried to find out whether the N-terminal fragment of glucogan-like peptide 1 receptor (nGLP-1R) still had binding activity to Exendin-4 after missing one or two gene segments. By error-prone PCR, We constructed a randomly mutated phage display peptide library with different length of the N-terminal (21-145 residues) extracellular domain of glucogan-like peptide 1 receptor (GLP-1R) from rat lung. A mutant named EP16 without binding activity was found by ELISA. Through sequence alignment we found that EP16 missed the first 20 and last 10 amino acids and the 52nd tryptophan was mutated to arginine. In order to determine why Ep16 did not show its binding ability to Exendin-4, a wild type EP16 without the first 20 and last 10 amino acids and nGLP-1R(W52R) was constructed in which the 52nd tryptophan was mutated to arginine. The contrastive analysis showed that the substitution of W52R led to a markedly reduced binding ability of EP16. The mutation of the conserved W52 could change the biologic activity of the protein. The lack of the first 20 and last 10 amino acids had no effect on its biologic activity. Therefore, the mutation of a single amino acid residue of the key sequence could change the biologic activity of the nGLP-1R.
Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Binding Sites ; Glucagon-Like Peptide-1 Receptor ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; Peptide Fragments ; chemistry ; genetics ; metabolism ; Peptides ; metabolism ; Protein Binding ; Rats ; Receptors, Glucagon ; chemistry ; genetics ; metabolism ; Venoms ; metabolism

Objective To determine the effect of signal transducers and activators of transcription 3 (STAT3) gene silencing by shRNA mediated by lentiviral vector for the treatment of colorectal cancer. Methods The recombinant lentiviral vector pRNAT-shSTAT3, empty lentiviral vector pRNAT-GFP, and lentiviral packaging plasmids in supernatant were collected to transfect HT-29 cells for harvesting the HT-29-shSTAT3 cells and HT29-GFP cells. Fifteen male rats were divided into three groups (n = 5 ), and then they were inoculated with HT-29cells, HT-29-GFP cells and HT-29-shSTAT3 cells, respectively. Cell growth was assessed by MTT assay and the changes in cell cycle were detected by flow cytometry. The changes in microvessel density (MVD) of tumors were detected by immunohistochemistry. All data were analysed by one-way analysis of variance. Results The growth of HT-29-shSTAT3 cells was significantly suppressed compared with HT-29 and HT-29-GFP cells (F = 632.50,P ＜ 0. 05 ). The proportions of cells at the G0/G1 phase were 68.7% ± 2.9% in HT-29-shSTAT3 cells, 38.5% ±1.6% in HT-29-GFP cells and 38.7% ± 2.3% in HT-29 cells, with a significant difference among the three groups (F = 166.53, P ＜ 0.05 ). The MVDs of HT-29 cells, HT-29-GFP cells and HT-29-shSTAT3 cells were 29 ±5, 28 ±4 and 10 ±3, respectively, with a significant difference among the three groups (F=31.60, P ＜0.05). Conclusion STAT3 gene silencing by shRNA mediated by lentiviral vector can significantly inhibit the growth of colorectal cancer cells.

Objective To study the correlation between expression of COX-2,Ki-67 and neoadjuvant chemotherapy in breast cancer.Method COX-2 and Ki-67 were examined by immunohistochemical staining in 48 breast cancer samples.Results The overall response rate and clinical benefit rate to neoadjuvant chemotherapy were 70.8% and 95.8%,respectively.The expression of COX-2 and Ki-67 after the chemothempy [41.7% and (33.23±18.11)%] was significantly lower than those in prechemotherapy [62.5% and (46.81±23.17)%],P<0.05.Ki-67 index Was higher in COX-2 positive tumom than that in the COX-2 negative ones before and after neoadjuvant chemotherapy,P<0.01.The effect of neoadjuvant chemotherapy had a significantly negative correlation with COX-2 expression.Patients with high expression of Ki-67 were more likely to respond to treatment.Conclusion The expression of COX-2 and Ki-67 as molecular markers could be a guide for chemotherapy and prediction for neoadjuvant's response to chemotherapy in breast cancer.

Objective To analyze the peculiarity of infants steroid-resistant nephrotic syndrome (SRNS) and to assess the efficacy,side-effect and relapse of various of Tacrolimus prescribed in infants SRNS.Methods A total of 76 case of infant SRNS from August 2012 to August 2015 in Guangzhou Weman and Children's Medical Center grouped into oral Tacrolimus (TAC group),Methyprenisolone pulse therapy (MP group) and Methyprenisolong combined Cyclophosphamide(CTX) pulse therapy(MP + CTX group),were observed for 1 year,and the urine protein excretion,renal function (CCr),blood glucose (B G),urine retinal-binding-protein (URBP),lymphocyte count etc.were recorded and the situation of infection and relapse regularly were monitored regularly.The data were retrospectively analyzed by the statistical method.Results All SRNS children underwent kidney biopsy,and 36 cases of minimal change disease,32 cases of mesangial proliferative glomerulonephritis and 8 cases of focal segmental glome-rulosclerosis were contained in the patients.The pathological constituent ratios were not obviously different among these 3 groups.By 6-month follow-up,the complete remission ratio of TAC group was 63.64％,the total remission ratio was 95.45％,which were remarkably higher than those of MP group (26.09％,60.87％) and MP + CTX group (41.94％,74.19％);the urine protein excretion of TAC group [(7.8 ± 8.6) mg/(kg · d)] was distinctly lower than that of pretreatment and lower than that of MP group [(144.2 ± 118.3) mg/(kg · d)],and lower than that of MP + CTX group [(91.3 ± 87.4) mg/(kg · d)],and the difference was significant (F =22.69,P ＜ 0.05).The remission time of TAC group was about 2 months,that of other two groups was about 3 months.By 1-year follow-up,the lymphocyte counts including total T-cell (CD3 +),the helper T-cell (CD4 +) and the inhibited T-cell (CD8 +) of TAC group decreased obviously(all P ＜ 0.01),which were extremely lower than those of the M P group and MP + CTX group,and there were significant differences (all P ＜ 0.05).By 1-year follow-up,the person-time of infection existed superior to the other 2 groups,TAC group was compared with MP plus group,the rank sum was 348.5 (U =-3.69,P ＜ 0.01);compared with MP + CTX plus group,the rank sum was 369.5 (U =-4.18,P ＜ 0.01).During the observation the URBP of TAC group was distinctly higher than that of the MP group and the MP + CTX group [(13.77 ± 19.19) mg/L vs.(2.50 ± 1.77) mg/L,(2.06 ±3.63) mg/L],and the differences were significant(t =3.16,2.99,all P ＜0.05);the TAC group with BG and CCr maintained stably.Conclusions Tacrolimus shows its own advantages of more reliable effect and less side-effect in the infants with SRNS over MP therapy and MP combined CTX therapy,but it could not lessen the recurrence of the disease,and its long-term prognosis is still not very clear.

Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone at different doses on the expression of CES1 and CES2. Imidapril and irinotecan hydrochloride (CPT-11) were used as special substrates for CES1 and CES2, respectively. Rat hepatocytes were cultured and treated with different concentrations of dexamethasone. The hydrolytic activity of CES1 and CES2 was tested by incubation experiment and their expression was quantitated by real-time PCR. A pharmacokinetic study was conducted in SD rats to further evaluate the effect of dexamethasone on CESs activity in vivo. Western blotting was performed to investigate the regulatory mechanism related to pregnane X receptor (PXR) and glucocorticoid receptor (GR). The results showed that exposure of cultured rat hepatocytes to nanomolar dexamethasone inhibited the imidapril hydrolase activity, which was slightly elevated by micromolar dexamethasone. For CES2, CPT-11 hydrolase activity was induced only when dexamethasone reached micromolar levels. The real-time PCR demonstrated that CES1 mRNA was markedly decreased by nanomolar dexamethasone and increased by micromolar dexamethasone, whereas CES2 mRNA was significantly increased by micromolar dexamethasone. The results of a complementary animal study showed that the concurrent administration of dexamethasone significantly increased the plasma concentration of the metabolite of imidapril while the ratio of CPT-11 to its metabolite SN-38 was significantly decreased. PXR protein was gradually increased by serial concentrations of dexamethasone. However, only nanomolar dexamethasone elevated the level of GR protein. The different concentrations of dexamethasone required suggested that suppression of CES1 may be mediated by GR whereas the induction of CES2 may result from the role of PXR. It was concluded that dexamethasone at different concentrations can differentially regulate CES1 and CES2.