Objective To observe the effects of valsartan and propranolol on the colonic mucosal microcirculation and submucosal ultra-structure changes in rats with portal hypertensive colopathy (PHC).Methods Portal hypertension(PHT) with cirrhosis was induced by composite factors after 42 days in rats.Rats were divided into a normal control group,a cirrhotic PHT model group,a treatment group with valsartan 20 mg/kg once daily,a treatment group with propranolol 22.5 mg/kg twice daily and a combination treatment group with propranolol and valsartan.The rats were treated for 15 days. The rats in the normal control group and the cirrhotic PHT model group were given water only.At the end of study,portal venous pressures(PVP) were measured.The submucosal vascular areas and metrical diameters of phlehectasia were measured by light microscope.The ultra-structure was observed by trans mission electron microscope.Results Compared to the cirrhotic PHT model group,PVPs were significantly decreased in the valsartan,propranolol,and combined groups (P

Objective To observe the clinical efficacy of mesalazine and bifid-triple viable combination therapy in patients with ulcerative colitis (UC).Methods Thirty-eight UC patients were evenly divided into mesalazine group and combination group. Patients in mesalazine group were administrated with mesalazine (1.0 g/time,four times/day),and on the basis of this,the patients in combination group were added into bifid-triple viable (420 mg/time,three times/day).The course of treatment was eight weeks.The improvement of patients' clinical symptom and manifestation under colonoscope were observed at second day after hospitalization and eight weeks after medication.Mayo disease activity index was used for scoring.Before and after the treatment,the expression of intestinal mucosa nuclear factor kappa B (NF-κB),tumor necrosis factor-α (TNF-a) and cyclooxygenase-2 (COX-2) were tested by immunohistochemical staining and the levels of serum TNF-α,interleukin-8 (IL-8), interleukin-10 (IL-10) were determined by double antibody sandwich enzyme-linked immunosorbent assay.The level of serum superoxide dismutase (SOD) and malondialdehyde (MDA) was detected by nitrite method and thiobarbituric acid coloration method.Before and after treatment was compared with paired t-test,and qualitative data was analyzed with ordinal rank sum test.Results Mayo disease activity index score of the combination group decreased from 7.16±2.01 to 1.63± 1.30 while the mesalazine group from 7.42 ± 1.95 to 3.00 ± 1.25.The difference of reduction was statistically significant (t =2.093,P =0.043).The efficiency of the combination group was higher than that of mesalazine group (16/19 vs 10/19,Fisher's exact test,P=0.039).After treatment,the expressions of NF-κB,TNF-α and COX-2 in colonic mucosa of two groups were both lower than those of before treatment,and in combination group the decrease were more significant (t value was 2.262,2.607 and 2.522 respectively,P value was 0.027,0.012 and 0.014 respectively).After treatment,the concentration of IL-8 of mesalazine group and the combination group both significantly decreased,however IL-10 significantly increased. The difference between these two groups was statistically significant (t value of TNF-α,IL-8 and IL-10 was 4.244,6.858 and 6.802 respectively,all P＜ 0.01). After treatment,both SOD vitality of two groups increased compare with that before treatment,however the level of MDA was lower than that before treatment and the changes of combination group were more significant.Conclusion The combination therapy with mesalazine and bifid-triple viable can effectively suppress inflammatory response in mild and moderate ulcerative colitis,and bifid-triple viable may play a role as adjuvant therapy for patients with UC.

Objective To investigate the suppression effects of tumor suppressor gene p53 alone and apoptosis incombination with TNF-? in a hepatocellular carcinoma cell line Hep3B. Methods Hep3B cells were transfected with a wild-type p53 cDNA(wt-p53)and plain vector(pNeo) respectively. Then the cell were cultured for 12 hours, one of the transfected p53 groups was added TNF-?(20 ?g/ml). The expression of p53 was detected by immunological fluorescence assay. Determination of apoptosis was used by DNA fragmentation, TUNEL assay. Results Both a small dose TNF-? and wt-p53 can induce apoptosis more efficiently comparing with non-transfected cultures(P

Objective: To investigate the effects of angiotensin II type 1 receptor antagonist valsartan on leptin, leptin receptor and collagen in rats with hepatic fibrosis. Methods: Thirty-six male wistar rats were randomly divided into control group, model group and drug-treated group, with 12 rats in each group. Liver fibrosis models were made by subcutaneous injection of carbon tetrachloride on the dorsal of the rats, simultaneously gastric gavage with Valsartan and were killed at the end of 8th week. The degree of liver fibrosis was observed by HE and Masson staining. The serum leptin (LP) and TGFβ1 were determined by ELISA. Liver LP mRNA and leptin receptor mRNA (OB-R mRNA) were detected by RT-PCR. Liver LP, OB-R and collagen I were detected by Western blot. The data of multiple groups were analyzed by one-way analysis variance (ANOVA), and linear correlation was performed between serum LP and TGF β1. Results: After the intervention of valsartan, HE and Masson staining showed that the degree of liver fibrosis was significantly reduced. The levels of serum LP and TGFβ1 in the control group were (18.92 ± 7.10) ng/ml and (9.13 ± 1.58) pg/ml respectively, which were significantly lower than those in the model group (46.92 ± 28.54) ng/ml and (16.39 ± 3.56) pg/ml, And (29.27 ± 7.27) ng/ml and (12.24 ± 2.94) pg/ml in the drug-treated group, respectively. The F values were 7.864 and 20.057 respectively. The P values were < 0.05. The differences were statistically significant. The relative expression levels of LP and OB-R mRNA in the control group were 0.35 ± 0.18 and 0.62 ± 0.18, respectively, which were significantly lower than those in the model group (1.79 ± 1.79 and 1.52 ± 1.44, and drug-treated group 0.48 ± 0.34 and 0.75 ± 0.26, respectively), F values = 6.914,3.894, P values were < 0.05, the differences were statistically significant. The relative expression levels of LP, OB-R and collaten I in liver were 0.71 ± 0.13, 0.81 ± 0.11 and 0.76 ± 0.13 in the model group, 0.97 ± 0.06, 1.04 ± 0.06, and 1.05 ± 0.04 respectively in the drug-treated group and 0.74 ± 0.05, 0.93 ± 0.05 and 0.91 ± 0.05. The F values were 15.425, 13.757 and 19.130 respectively in three groups (P < 0.001), the difference was statistically significant. Conclusion Valsartan, an angiotensin II type 1 receptor antagonist, can reduce the expression of leptin and leptin receptor, reduce the production of TGFβ1 and collaten I, and play an anti-hepatic fibrosis effect.

Objective To study the clinical characteristic of non puerperal mastitis and estimate the effect of anti-mycobacterial agents for non puerperal mastitis .Methods 22 cases of periductal mastitis and gran-ulomatous mastitis receiving anti-mycobacteria drugs therapy from Mar .2012 to Mar.2014 were retrospectively analyzed.Results All patients were female.The mean age was 30 years(ranging from 24 to 46 years).The main clinical manifestation of the 22 patients were 18 patients(81.8%)with mass, 20 patients(90.9%)with abscess, 15 patients(68.2%)with fistula and 9 patients(40.9%)with all of the above 3 symptoms.6 patients had incision and drainage of abscess and 2 patients had tumor resection before anti-mycobacterial therapy .All of the 8 patients had postoperative recurrence .All patients underwent anti-mycobacterial therapy with 3 to 16 months.11 cases (50.0%)patients were cured without recurrence until now .7 cases(31.8%) patients were improved markedly and they still received drug treatment .2 cases(9.0%)patients with tumor size reduced to 2 cm were ready to sur-gical resection.2 cases(9.0%)were lost to follow-up.Conclusion Patients with refractory non puerperal masti-tis can be treated with anti-mycobacterial agents with relatively long treatment time and can also avoid mastecto-my.

Background:Chronic constipation is a major cause of impaired quality of life in modern society. Reasonable and effective management of chronic constipation could be achieved based on the principle of evidence-based medicine and the modern concept of constipation,and this is a challenge facing the clinicians. Aims:To investigate the role of barium-based colonic transit detection in diagnosis and treatment of chronic constipation. Methods:Fifty patients with chronic constipation from Apr. 2013 to Oct. 2014 at the First Hospital of Shanxi Medical University were recruited and randomly allocated into two groups,control group and individualized treatment group. Patients in individualized treatment group received 20 barium markers orally and abdominal plain radiography was performed 48 and 72 hours later,respectively for calculating the colonic transit index. According to the type of colonic transition and the characteristics of colonic motility estimated by colonic transit index and clinical manifestations,an individualized therapeutic regimen was formulated and the efficacy was evaluated. Patients in control group were treated empirically according to the clinical manifestations. Results:Mosapride and lactulose or polyethylene glycol were administered orally in control group;when abdominal pain or abdominal distension was predominant,pinaverium bromide or trimebutine was used respectively instead of mosapride. Barium-based colonic transit detection revealed that 9 patients in individualized treatment group were slow transit constipation,6 were outlet obstructive constipation and 8 were the mixed type. After 2 weeks of empirical or individualized treatment,the defecation rates of the two groups were 24. 0%(6 / 25)and 52. 2%(12 / 23)within 24 hours and 64. 0%(16 / 25)and 87. 0%(20 / 23)within 48 hours,respectively(P all < 0. 05). Conclusions:Barium-based colonic transit detection is a simple,economical and practical modality for guiding the individualized treatment in patients with chronic constipation.

Objective: To investigate the effect of interleukin-22 (IL-22) on the activation and proliferation of hepatic stellate cells (HSCs) induced by acetaldehyde, as well as the role of the antioxidant axis Nrf2-keap1-ARE. Methods: Hepatic stellate cell-T6 (HSC-T6) cells were cultured in vitro, and after 24 and 48 hours of acetaldehyde stimulation at various concentrations (25, 50, 100, 200, and 400 μmol/L), MTT assay was used to measure cell proliferation rate to screen out the optimal conditions for model establishment. HSC-T6 cells were treated first with the optimal concentration of acetaldehyde (200 μmol/L) for 24 hours and then with different concentrations of IL-22 (10, 20, and 50 ng/ml) for 24 hours. MTT assay was used to measure cell proliferation, Western blot and cell immunohistochemistry were used to measure the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and α-smooth muscle actin (α-SMA), and spectrophotometry was used to measure the changes in the content of malondialdehyde (MDA) and reduced glutathione (GSH) in culture supernatant. SPSS 17.0 was used for statistical analysis and data were expressed as mean±SD. P < 0.05 was considered statistically significant. A one-way analysis of variance was used for comparison of means between any two groups. Results: HSCs had significantly enhanced proliferation and activation after being treated with acetaldehyde, especially at 200 μmol/L for 48 hours. After the intervention with gradient concentrations of IL-22, the proliferation and activation of HSCs were inhibited in a dose-dependent manner, and the proliferation and migration rates in the 10, 20, and 50 ng/ml IL-22 groups were 14%, 25%, and 35%, respectively (all P < 0.05). The results of Western blot and immunohistochemistry showed that there was no significant difference in the expression of Nrf2 total protein in HSCs between groups, while there was extremely low expression of Nrf2 nucleoprotein in the blank control group. There was increased expression of Nrf2 nucleoprotein after acetaldehyde stimulation (compared with the blank control group, P < 0.05), and after the intervention with gradient concentrations of IL-22, the expression of Nrf2 nucleoprotein was further increased (all P < 0.05). The results of spectrophotometry showed that compared with the blank control group, the model group had increased levels of MDA and GSH in culture supernatant after acetaldehyde stimulation; after the intervention with gradient concentrations of IL-22, there was a significant reduction in the MDA level and a significant increase in the GSH level in a dose-dependent manner (all P < 0.05). Conclusion The activation and proliferation of HSCs induced by acetaldehyde helps with the successful establishment of an in vitro model of alcoholic liver fibrosis. IL-22 effectively inhibits the activation and proliferation of HSCs induced by acetaldehyde, and its mechanism may be related to promoting Nrf2 nuclear translocation in HSCs and expression of the downstream target gene GSH and increasing the activity of the antioxidant axis Nrf2-keap1-ARE.

Objective:To explore the expression and clinical significance of S100A8 and S100A9 in Helicobacter pylori ( H. pylori) associated gastritis. Methods:A total of 101 patients with chronic gastritis diagnosed in the First Hospital of Shanxi Medical University from October 2018 to May 2019 were selected. The expression levels of S100A8 and S100A9 in the gastric mucosa tissues of 101 patients with chronic gastritis were determined by immunohistochemistry (in absorbance), and the mRNA expression levels of S100 A8 and S100 A9 in the gastric mucosa tissues of 48 patients were detected by reverse transcription-polymerase chain reaction. And the results combined with pathological diagnosis of routine staining and clinical H. pylori infection data were analyzed. Mann-Whitney U test, Kruskal-Wallis H test and Spearman rank correlation were used for statistical analysis. Results:Among 101 patients, there were 59 cases of chronic atrophic gastritis (CAG group) and 42 cases of chronic non-atrophic gastritis (NAG group); 59 cases were H. pylori positive ( H. pylori positive group) and 42 cases were H. pylori negative ( H. pylori negative group). There were statistically significant differences in the expression levels of S100A8 and S100A9 between CAG group and NAG group (0.10, 0.07 to 0.13 vs. 0.09, 0.06 to 0.10 and 0.13, 0.08 to 0.15 vs. 0.09, 0.07 to 0.10, respectively), and between H. pylori positive group and H. pylori negative group (0.11, 0.10 to 0.13 vs. 0.07, 0.06 to 0.08 and 0.13, 0.10 to 0.15 vs. 0.07, 0.07 to 0.08, respectively) ( U=754.00, 602.00, 5.00 and 40.00, all P<0.01). There were statistically significant differences in the expression levels of S100A8 and S100A9 between H. pylori positive patients (34 cases) and H. pylori negative patients (25 cases) in CAG group (0.13, 0.11 to 0.14 vs. 0.07, 0.07 to 0.08 and 0.15, 0.14 to 0.16 vs. 0.08, 0.08 to 0.09, respectively), similarly, there were significant differences in the expression levels of S100A8 and S100A9 between H. pylori positive patients (25 cases) and H. pylori negative patients (17 cases) in NAG group (0.10, 0.09 to 0.10 vs. 0.06, 0.05 to 0.07 and 0.10, 0.10 to 0.11 vs. 0.07, 0.06 to 0.07, respectively) ( U=1.00, 0.00, 0.00 and 0.00, all P<0.01). The results indicated that the expression levels of S100A8 and S100A9 were high in H. pylori positive patients in CAG group, the expression levels of S100A8 and S100A9 were low in H. pylori negative patients in NAG group, and the differences were statistically significant ( H=84.78 and 89.64, both P<0.01). There were statistically significant differences in the expression of S100 A8 and S100 A9 at mRNA level between CAG group (24 cases) and NAG group (24 cases) (0.12, 0.06 to 1.31 vs. 0.05, 0.03 to 0.08; 0.19, 0.03 to 0.43 vs. 0.03, 0.01 to 0.09), and the expression of S100 A8 and S100 A9 at mRNA level was significant between H. pylori positive patients (24 cases) and H. pylori negative patients (24 patients) (0.45, 0.10 to 1.90 vs. 0.05, 0.03 to 0.08 and 0.36, 0.24 to 0.81 vs. 0.03, 0.01 to 0.04) ( U=55.00, 74.00, 19.00 and 2.00, all P<0.05). There were statistically significant differences in the expression of S100 A8 and S100 A9 at mRNA level between H. pylori positive patients (12 cases) and H. pylori negative patients (12 cases) of CAG group (0.85, 0.27 to 2.28 vs. 0.06, 0.03 to 0.09 and 0.39, 0.25 to 0.87 vs. 0.03, 0.02 to 0.05), and the expression of S100 A8 and S100 A9 at mRNA level was significant between H. pylori positive patients (12 cases) and H. pylori negative patients (12 cases) of NAG group (0.09, 0.05 to 0.28 vs. 0.04, 0.03 to 0.07 and 0.20, 0.09 to 0.65 vs. 0.01, 0.01 to 0.03) ( U=5.00, 2.00, 0.00 and 0.00, all P<0.01). The results showed that the expression of S100 A8 and S100 A9 at mRNA level was high in H. pylori positive patients in CAG group, the expression of S100 A8 and S100 A9 at mRNA level was low in H. pylori negative patients in NAG group, and the differences were statistically significant ( H=20.43 and 24.15, both P<0.01). The expression levels of S100A8 and S100A9 were positively correlated at both protein level and mRNA level ( r=0.899 and 0.903, both P<0.01). Conclusions:S100A8 and S100A9 may involve in the inflammation process of H. pylori-infected gastric mucosa and promote the proliferation of gastric epithelial cells, which may be one of mechanisms of intrinsic glands reduction and CAG genesis. S100A8 and S100A9 are expected to be potential biomarkers for diagnosis and follow-up and potential targets for treatmert of CAG.

Objective: To investigate the effects of Helicobacter pylori (H.pylori) on the proliferation of GES-1 cells and the expressions of S100A8 and S100A9 in human gastric epithelial cell line GES-1. Methods: H. pylori were co-cultured with GES-1 cells at different infection plural (muhiplieity of infection (MOI) 50∶1, 100∶1, 200∶1), then the cells and cell culture supernatants were collected. The proliferative activity was detected by cell counting kit 8 (CCK-8) methods. The expression of S100A8 and S100A9 at mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). The levels of S100A8 and S100A9 proteins and tumor necrosis factor-alpha (TNF-α) in cell culture supernatants were measured by enzyme linked immunosorbent assay (ELISA). T test and Pearson method were performed for statistical analysis. Results: The negative control group was taken as the baseline, the proliferation rates of GES-1 cells of the H. pylori multiplicity 50∶1 group, 100∶1 group and 200∶1 group were (105.51±4.78)%, (168.97±11.29)% and (64.05±10.11)%, respectively. There was no statistically significant difference in the proliferation rate of GES-1 cells between H. pylori multiplicity 50∶1 group and negative control group (t=0.69, P=0.51). The proliferation rate of GES-1 cells of the H. pylori multiplicity 100∶1 group was higher than that of the negative control group, and the difference was statistically significant (t=10.63, P<0.01). The proliferation rate of GES-1 in the H. pylori multiplicity 200∶1 group was lower than that of the negative control group, and the difference was statistically significant (t=-5.54, P<0.01). The expression of S100A8 and S100A9 at the mRNA level in the H. pylori multiplicity 200∶1 group was 0.31±0.21 and 8.66±4.08, respectively, which were higher than those of the negative control group (0.06±0.05 and 0.08±0.08), and the differences were statistically significant (t=10.20 and 6.89, both P<0.05). The expressions of S100A8 at the protein level of H. pylori multiplicity 50∶1, 100∶1, and 200∶1 groups were (112.21±1.25) ng/mL, (120.39±1.61) ng/mL and (121.28±0.71) ng/mL, respectively; while the expression of S100A9 at the protein level were (179.43±2.44) ng/mL, (191.47±1.98) ng/mL and (201.80±2.06) ng/mL, respectively; and the expression of TNF-α levels were (285.52±3.64) ng/mL, (320.08±2.28) ng/mL and (350.97±2.90) ng/mL, respectively; which were all higher than those of the negative control group ((76.14±1.30) ng/mL, (161.35±1.31) ng/mL and (270.08±2.96) ng/mL, respectively), and the differences were statistically significant (t_S100A8=35.09, 43.06, 43.92, t_S100A9 = 11.13, 18.54, 24.90, t_TNF-α= 6.34, 20.54, 33.23; all P<0.01). The expressions of S100A8 and S100A9 at the protein level were positively correlated with TNF-α (r=0.92 and 0.95, both P<0.01). Conclusion S100A8 and S100A9 may be involved in the process of H. pylori induced proliferation disorder and inflammation in GES-1 cells.

OBJECTIVETo explore the effect of the Hsp90 inhibitor anacardic acid on cell proliferation, invasion and migration of breast cancer MDA-MB-231 cells.

METHODSThe inhibitory effect of anacardic acid on Hsp90 was assessed with in vitro ATPase inhibition assay and ATP-sepharose binding assay. MTT assay was used to detect the growth inhibition induced by anacardic acid in MDA-MB-231 cells. Transwell assays were used to evaluate MDA-MB-231 cell invasion and migration. Western blotting was performed to assess the effect of anacardic acid in triggering the degradation of MMP-9, TIMP-1, Hsp90, and Hsp70.

RESULTSAnacardic acid exhibited a modest activity of ATPase inhibition with an IC50 value of 82.5 µmol/L. Anacardic acid significantly suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner (IC50 value of 29.3 µmol/L). Treatment with 12.5, 25, and 50 µmol/L anacardic acid for 36 h caused inhibition of cell invasion by 23.6%, 56.6%, and 67.0% in MDA-MB-231 cells, respectively (P<0.05), and anacardic acid treatment for 24 h inhibited the cell migration by 30.0%, 45.5%, and 77.5%, respectively (P<0.05). Anacardic acid dose-dependently induced MMP-9 degradation, but did not obviously affect Hsp90 or Hsp70 expressions.

CONCLUSIONAnacardic acid can significantly inhibit the proliferation, invasion, and migration of MDA-MB-231 cells, the mechanism of which may involve the inhibition of Hsp90 ATPse activity and down-regulation of MMP-9 expression.

Anacardic Acids ; pharmacology ; Breast Neoplasms ; pathology ; Cell Line, Tumor ; drug effects ; Cell Movement ; Cell Proliferation ; Down-Regulation ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism