Objective To investigate the changes in acetylation of histone in the spinal dorsal horn in a rat model of persistent postoperative pain.Methods Ninety-six malc Sprague-Dawley rats,weighing 200-250 g,aged 6-8 weeks,were randomly divided into 2 groups (n=48 each) using a random number table:sham operation group (group S) and persistent postoperative pain group (group PPP).The rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established according to the method described by Flatters.After the rats were anesthetized with intraperitoneal chloral hydrate,the skin and superficial muscle of the medial thigh were incised and retractors inserted.This tissue was retracted for 1 h.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before operation and 1,3,7,14,and 21 days after operation.Four animals were sacrificed in each group after measurement of MWT at each time point for detection of acetylated histone H3 (Ac-H3) and acetylated histone H4 (Ac-H4) expression (by Western blot analysis) and the number of Ac-H3 and Ac-H4 positive cells in the spinal cord horn (by immunofluorescence histochemistry).Results Compared with group S,the MWT was significantly decreased at 3,7,14 and 21 days after operation,the expression of Ac-H3 and Ac-H4b was significantly down-regulated at 3,7 and 14 days after operation,and the number of Ac-H3 and Ac-H4 positive cells was significantly decreased at 7,14 and 21 days after operation in group PPP (P＜0.05 or 0.01).The MWT,expression of Ac-H3 and Ac-H4b,and the number of Ac-H3 and Ac-H4 positive cells were significantly higher at 21 days after operation than at 14 days after operation in group PPP (P＜0.05).Conclusion Acetylation of histone in the spinal dorsal horn is decreased after operation,which may be involved in the development and maintenance of persistent postoperative pain in rats.

Objective To evaluate the effect of heat treatment on ultraviolet B (UVB)-induced oxidative injury to human melanocytes.Methods Melanocytes were isolated from adult foreskins,and subjected to a primary culture.After 3-4 passages of subculture,the melanocytes were classified into 4 groups:control group incubated at 37 ℃,heat treatment group incubated at 42 ℃ for 1 hour,UVB group exposed to UVB irradiation at 100 mJ/cm2,combination group receiving heat treatment at 42 ℃ for 1 hour followed by UVB irradiation at 100 mJ/cm2.After three successive days of treatment,MTT assay was performed to evaluate cell viability,a biochemical method to determine the activity of superoxide dismutase (SOD) and concentration of malonaldehyde (MDA),and flow cytometry to detect intracellular reactive oxygen species (ROS) and apoptosis in melanocytes.Results The cell survival rate,apoptosis rate,SOD activity,MDA concentration and ROS level were (100 ± 6.14)％,(4.66 ± 0.58)％,(53.39 ± 8.23) U/gprot,(1.09 ± 0.32) mmol/gprot,and 1070.85 ± 42.07 in the control group respectively.UVB exposure induced a significant increase in apoptosis rate (24.14％ ± 2.90％,P ＜ 0.001),MDA concentration (1.65 ± 0.33 mmol/gprot,P ＜ 0.01) and ROS level (1416.45 ± 79.12,P＜ 0.01),but a significant decrease in cell survival rate (50.23％ ± 5.36％,P＜ 0.01)and SOD activity (31.98 ± 1 1.89 U/gprot,P ＜ 0.01) in the UVB group compared with the control group,while the heat pretreatment markedly downregulated the UVB-induced increase in apoptosis rate (14.9％ ± 1.49％,P ＜ 0.001),MDA concentration (1.10 ± 0.26 mmol/gprot) and ROS level (1033.30 ± 68.41,P＜ 0.01),as well as the decrease in cell survival rate (74.12％ ± 6.17％,P＜ 0.01) and SOD activity (51.63 ± 6.55 U/gprot,P＜ 0.01) in the combination group.Conclusion Heat treatment could protect melanocytes from UVB-induced oxidative injury.

Purpose To investigate the responsiveness of intracellular oxygen free radical and calcium on acrolein exposure and acrolein-induced cardiomyocytes apoptosis. Methods The viable adult mice cardiac myocytes were isolated by modified langendorff methods. We have examined the intracellular oxygen free radical and calcium concentration using DCF and Fura-2 AM, and the cardiomyocytes viability with WST assay. Are evaluated the DNA ladder pattern and cell apoptotic morphology on the adult mice cardiomyocytes that are exposed to acrolein. Results Our results show that acrolein can increase markedly the intracellular oxygen free radical and calcium concentration, that reach 12 fold and twofold respectively compared to the resting value when the cells were exposed to 1 μmol/L of acrolein. Moreover, the injury induced by acrolein in cardiac myocytes is concentration-dependent. The cardiomyocytes viability treated with 25, 50, 100 μmol/L of acrolein respectively were significantly lower compared to controls (P ＜ 0.01 ). DNA ladder pattern and apoptotic morphological changes were found after being exposed to acrolein in the adult mice cardiomyocytes. Conclusion It is concluded that acrolein induces adult mice cardiomyocytes apoptosis, and it may be due to the increased intracellular oxygen free radicals and calcium concentration.

Objective To evaluate the effect of multiple adhesion molecules ICAM-1、CD_ 44 V6、CD_ 28 、E-cad and CEA in organic selection of gastric carcinomatous metastasis.Methods Eighty-four gastric carcinoma cases(32 cases without metastases,52 cases with transfer to liver、marrow、lymphonode、lung、kidney or belly cavity),were take operation sample or tissue under gastroscopy,being made cells single by primary culture,then were detected the expression of 5 kinds of adhesion molecules by ABC immunohistochemistry,positive rate was recorded.Results ICAM-1 had high expression in cases with marrow or lung metastasis,while low expression in cases with lymphonode metastasis.CD_ 44 v6 had high expression in cases with lymphnode or liver metastasis.CD_ 28 had high expression in cases with liver、lung or kidney metastasis.E-cad had high expression in cases with marrow metastasis,while low expression in cases with other metastasis.CEA had especially high expression in cases with liver、belly cavity or lymphnode metastasis.Conclusion High or low expression of adhesion molecules ICAM-1、CD_ 44 V6、CD_ 28 、E-cad and CEA plays a certain role in organic selection of gastric carcinomatous metastasis.

OBJECTIVE:To study the incidence of adverse drug reactions(ADRs) and the rational use of Durogesic in in-patients METHODS:37 in-patients treated with Durogesic in Department of Oncology in our hospital were prospectively observed,and its analgesic efficacy and incidence,severity and the outcome of ADRs were evaluated RESULTS:The alleviating effect of Durogesic on carcinomatous pain was 100% Of 37 patients,ADRs were found in 4 cases with a ADR rate of 10 8% CONCLUSION:Durogesic is effective in clinical use,but attention should be paid to monitoring ADRs and avoiding irrational use of drug

Objective To investigate the relationship between miR-411 and breast cancer,and the expression of miR-411 and its effects and mechanism research on proliferation and metastasis in breast cancer.Methods Real-time polymerase chain reaction (RT-PCR) was used to detect the expression of miR411 in breast cancer cells and tissues.Methyl thiazolyl tetrazolium (MTT),clone formation assay and Transwell assay were used to detect the effect of miR-411 expression on the proliferation,migration and invasion in breast cancer cells.The effect of miR-411 on growth factor receptor-bound protein 2 (GRB2) expression in breast cancer cells was detected by RT-PCR and Western blot.The direct effect of miR-411 target on GRB2 was detected by dual luciferase reporter assay.MTT,clone formation assay and Transwell assay detect the effect of GRB2 expression on the proliferation and invasion in breast cancer cells.Detection the effect high expression of miR-411 on GRB2 downstream signaling pathway related molecules expression in breast cancer cell with Western blot.Results The expression of miR-411 in breast cancer tissues was significantly lower than that in adjacent non-cancerous tissues (P ＜ 0.05).The expression of miR-411 in breast cancer cells SK-BR-3,BT-549 and MDA-MB-231 was significantly lower (P ＜ 0.05).Compared to the negative control group,the transfection of miR-411 mimic inhibited the proliferation,migration and invasion of MDA-MB-231 breast cancer cells (P ＜ 0.05).Targetscan showed that miR-411 could bind to GRB2 3'UTR at position 741-747.Compared with the negative control group,GRB2 3'UTR wild-type plasmid and miR-411 co-transfection reduced the fluorescence activity (P ＜ 0.05).Transfection of siGRB2 significantly reduced the expression of GRB2 protein in MDA-MB-231 breast cancer cells (P ＜ 0.05).Compared to the negative control group,the inhibition of GRB2 expression reduced the proliferation and the number of colony formation of MDA-MB-231 breast cancer cells (P ＜ 0.05).Transwell assay showed that transfection of siGRB2 significantly reduced the number of invasive cells in MDA-MB-231 breast cancer cells (P ＜ 0.05).Conclusions miR-411 is related closely to the occurrence and development of breast cancer,miR-411-GRB2-Ras axis is expected to become a new target for biological treatment of breast cancer.

Objective To observe the clinical effects of pemetrexed alone or pemetrexed combined with platinum in the treatment of advanced non -squamous non -small cell lung cancer who failed first line therapy. Methods 34 patients with advanced NSCLC who had failed to previous chemotherapy and all of these patients had been confirmed with pathology or cytology.Pemetrexed monotherapy group included 14 cases and pemetrexed plus platinum group included 20 cases.21 days as one cycle.All patients who received 2 or more cycles could be evaluated. Results No complete response (CR)occurred.There were 3 cases of partial response (PR),15 cases of stable disease(SD)and 16 cases of progressive disease(PD)in the 34 patients.The disease control rate was 52.9%(18 /34).The median progressive free survival was 2.7 months.The major toxic reaction included leucopenia,anemia and gastrointestinal response.Conclusion Pemetrexed or pemetrexed combined with platinum can prolong the survival time of some patients of non -squamous non -small cell lung cancer who failed first line therapy.The toxic effects can be tolerated.

Objective To observe the changes of mechanical pain thresholds and autophagy related proteins microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (SQSTM1 also known as p62) expression levels in the C57BL/6 mouse models of chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS),and provide animal experimental evidence for CP/CPPS pain and autophagy study.Methods 36 male C57BL/6 mice were randomly divided into three groups: the model group,control group and na(i)ve group.The CP/CPPS model was established by subcutaneous injection in the lower abdomen region with suspension liquid,containing protein extract of male SD rat prostate gland and complete Freund adjuvant.At 1month and 6 months after modeling,the mice were sacrificed and prostate tissues were harvested for histological examination using HE staining.Mechanical tactile hyperalgesia was measured with von Frey filaments.The autophagy-related proteins LC3 and p62 expression levels were detected by immunohistochemistry,respectively.The average IOD was measured by Image Pro Plus 6.0,and the statistical analysis was performed with GraphPad Prism 5 software.Results The histopathology showed the appearance of chronic prostatitis in the model group,representing hyperplasia and lymphocytic infiltration to a different degree and lasted for 6 months after modeling.Moreover,prostate intraepithelial neoplasia (PIN) appeared in the model group at 6 months after modeling,characterized by the disappearence of basement membrane and obvious nuclear abnormality,while the control and na(i)ve groups showed normal histology during the 1-6 months.Compared with the control and na(i)ve groups,the mechanical pain threshold in the model group was significantly decreased along with the time from (0.353±0.154) g at 0 week to (0.008±0.00) g at 22 weeks (P<0.05).The average IOD of LC3 and p62 expression in the model group was significantly increased with timing from [(2.767±0.464)%,(2.872±1.642)%] at 1month to [(13.501±1.900)%,(9.07±0.49)%] at 6 month,P<0.05.Conclusions A CP/CPPS model is successfully established in C57BL/6 mice.For the model group,the mechanical pain threshold is decreased and autophagy levels are increased gradually with time.These phenomena show that chronic inflammation microenvironment may promote pain and autophagy activity in the prostate,which is closely related with the occurrence and development of prostatic intraepithelial neoplasia.

for the detection of their virulent abilities simultaneously.

Objective To observe the efficacy and untoward reactions of FOLFOX4 regimen and XELOX regimen in the treatment of patients with advanced colorectal cancer.Methods Fifty four advanced colorectal cancer patients were randomly divided into two groups.Group A (FOLFOX4):28 patients were treated with oxaliplatin 85 mg/m2 on day 1,LV 200 mg/m2 as a 2h infusion followed by bolus 5 -FU 400 mg/m2 and a 24h infusion of 5 -Fu 600 mg/m2 ,repeated for consecutive days every 2 weeks.One cycle was 14 days and efficacy was evaluated after 4 cycles.Group B(XELOX):26 patients were treated with oxaliplation 130mg/m2 on day 1,capecitabine 1 000 mg/m2 orally daily for 14 days.One cycle was 21 or 28 days and efficacy was evaluated after 2 cycles.Efficacy of the two groups was evaluated at 2 cycles.Results All 54 patients were available for evaluating objective response.In A group,the overall response rate was 46.4%,and the overall response rate was 42.3% in B group.The overall response rate of A group was slightly higher than B group,but there was no statistically significant difference(χ2 =0.093,P =0.791 ).Adverse reactions:thrombocytopenia incidence rate and the peripheral nerve toxicity had no significant differences between the two groups(χ2 =0.552,0.108,P =0.550,0.787).The incidence rates of nausea, vomit,diarrhea and leucocytopenia in B group were lower than those in A group(χ2 =9.495,4.862,6.273,P =0.003,0.033,0.108).The incidence rate of hand -foot syndrome was higher in B group than in A group(χ2 =13.389,P =0.000),but the severity was less(grade Ⅰ ~Ⅱ).Conclusion The response rate in the treatment of advanced colorectal cancer was similar between XELOX and FOLFOX4 regiments,but XELOX regiment has the advantages of more convenience,better safety.Thus,XELOX regiment is worth recommending as a first -line therapy for the treatment of patients with advanced colorectal cancer.