Current goals of ulcerative colitis treatment include rapid remission,steroid-sparing remission,endoscopic mucosal healing,reduction in hospitalization and surgery and improvement in quality of life.The treatment principle is rational medications according to the severity,activity and extent of the disease with individualized and comprehensive treatment.The medications conventionally used are 5-ASA,GCS and IS.Newly developed biological agents like Anti TNF-?(infliximab)are used in severe UC and refractory cases.Traditional Chinese Medicines have been used in more than 80% of UC cases and will play a great role in the future.The indications for surgery include acute perforation,massive hemorrhage,toxic megacolon,malignancy and refractory cases for medical therapy.

Objective To investigate the expression and significance of human β-defensin-2 (HBD2),TNFα and IL-1βin ulcerative colitis(UC).Methods Thirty-five patients with active UC diagnosed by the department of gastroenterology in West China Hospital were included in this study.Ulcerative colitis disease activity index(UCAI)was assessed and the pathological grades of UC were classified.Immunohistochemistry assay and real-time quantitative PCR were used for the expression of HBD2,TNFα,IL-1β in colonic mucosa of UC.Results Among the 35 patients with UC,10 cases were mild.13 moderate and 12 severe.Of the 35 cases.there were 11 with grade Ⅰ.13 grade Ⅱ and 11 grade Ⅲ lesion according to Truelove criteria.The score of UCAI had positive correlation with pathological grading (r=0.890,P＜0.01).The expressions of HBD2,TNFα,IL-1β in colonic mucosa of UC with immunohistochemistry and real-time quantitative PCR were significantly higher than those in healthy control (P＜0.05);the expressions increased gradually with the severity of pathological grade and there was a higher expression of them in inflamed area than in non-inflamed(P＜0.05).A good positive correlation was also found between HBD2 and other inflammatory cytokines.Conclusions It is shown that there is a higher expression of HBD2 in colonic mucosa as compared with healthy control.a higher expression of it in inflamed area than in non-inflamed area and a positive correlation of expression between HBD2 and pro-inflammatory cytokines such as TNFα and IL-1 β,implying that HBD2 and pro-inflammatory cytokines are interdependent and interactive playing an important role in magnifying and aggravating inflammatory injury in UC.

Objective: To investigate the therapeutic effects of Bawei Xilei San (BWXLS), a compound traditional Chinese herbal medicine, on mice with oxazolone-induced colitis and to explore the mechanisms. Methods: Thirty-two BALB/c mice were randomly divided into 4 groups (8 for each): normal control group, untreated group, hydrocortisone group and BWXLS group. Except for the mice in the normal control group, all mice were intrarectally administered with 3.0% oxazolone to induce colitis. Then the mice in the normal control group and untreated group were administered with 0.9% carboxymethyl cellulose sodium solution. Mice in the BWXLS group were intrarectally administered with 0.2 mg/g BWXLS and hydrocortisone group with 0.02 mg/g respectively for 5 days. The body weight and stool consistency and occult or gross blood were recorded to calculate the disease activity index (DAI). The mice were sacrificed at the 6th day. The macroscopic and histological changes of the colon were evaluated. The expressions of Toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-kappaB), and epithelial tight junction protein occludin were assessed by immunohistochemical method. The level of tumor necrosis factor-alpha (TNF-alpha) in colonic mucosa was evaluated by enzyme-linked immunosorbent assay. Results: The DAI, and macroscopic and histological changes in the BWXLS group were improved as compared with those in the untreated group (P<0.05) but were similar to those in the hydrocortisone group. The expression of occludin was significantly increased (P<0.05) while the expressions of TLR4, NF-kappaB and TNF-alpha were significantly decreased in the BWXLS group as compared with the untreated group, and were similar to those in the hydrocortisone group (P>0.05). Conclusion: Up-regulating the expression of occludin and down-regulating the expressions of TLR4 and NF-kappaB, and hence inhibiting TNF-alpha expression and improving the mucosa barrier function may be part of the mechanisms of BWXLS in treating oxazolone-induced colitis in mice.

Objective To investigate the expressions of 5-lipoxygenase (5-LOX) protein and mRNA in colon mucosa of ulcerative colitis (UC) and to analyze its correlation with endoscopic and histological grading. Methods The biopsies from 32 UC patients and 26 healthy controls were collected, and the expressions of 5-LOX mRNA and protein in colonic mucosa was determined by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry assay, respectively. The endoscopic and histological grading of 32 UC patients were also recorded. Results According to endoscopic grading, there were 10 cases of grade Ⅰ , 19 of grade Ⅱ and 3 of grade Ⅲ in 32 UC patients, and there were 19 cases of grade Ⅰ , 9 of grade Ⅱ and 4 of grade Ⅲ according to histological grading. The expressions of 5-LOX mRNA and protein in UC patients were significantly higher than those in healthy controls (P ＜0. 05 ). The rate of 5-LOX protein expression increased with endoscopic and histological grades, which was also positively correlated with endoscopic grades ( P ＜ 0. 05 ), but not with histological grades ( P ＞0. 05 ). Conclusion The expressions of 5-LOX mRNA and protein in colon mucosa from UC patients might be a marker for disease activity. 5-LOX may play a pivotal role in inflammation of UC and be a target site for treatment.

Objective To investigate the effect of pioglitazone on oxazolone-induced colitis and to clarify the mechanism of apoptosis by Fas/Fas ligand(FasL). Methods Eighteen BALb/c mice of ulcerative colitis induced by oxazolone enema were equally allocated into 3 groups. The mice in group 1 were sacrificed 3 days after enema,lamina propria mononuclear cells(LPMC) were isolated from freshly obtained colonic specimens and treated in vitro with pioglitazone (40 ?mol/L),the annexin-V-FITC was used for detection of apoptosis,and Fas/FasL expression was assayed by flow cytometry. Meanwhile,untreated mice were served as normal controls. Mice in group 2 (control group) and 3 (experiment group) were treated with methylcellulose or pioglitazone(20 mg?kg -1 ?d -1 ) 3 days after enema and were administrated for consecutive 7 days. The colonic inflammation including disease activity index (DAI),macroscopic and histological changes,myeloperoxidase(MPO) activity and levels of interleukin (IL)-4,IL-5 were evaluated. Results Apoptosis of LPMC,expression of Fas and FasL in normal and colitis mucosa were 12.89?1.23,70.63?6.24,8.59?5.47 and 4.25?0.84,62.60?5.85,23.75?10.23,respectively. After treated with pioglitazone,both apoptosis of LPMC and expression of Fas increased,while FasL expression decreased (40.58?10.32,83.98?11.38 and 10.04?5.21 respectively). In group 2 and group 3,the macroscopic and microscopic score,MPO activity,IL-4 and IL-5 level were 2.50?0.55,8.83?0.75, 3.81?0.17,216.46?34.32,102.28?25.74 and 0.33 ?0.52,4.00?0.63,1.25?0.16,179.36?18.15,61.65?17.45,respectively. Conclusion The results indicate that pioglitazone treatment can significantly attenuate colonic inflammation,and it might be related to the apoptosis of LPMC through Fas and FasL.

p53 gene mutations and their expression in protein levels of colorectal adenomas, carcinomas and regional lymph nodes metastasis were detected by PCR-SSCP and AB-PAP immunohistochemical analysis, respectively. The results showed that p53 gene mutations were detected in 25% colorectal adenomas, 80% carcinomas and 100% regional lymph nodes metastasis. Meanwhile, p53 proteins were detected at rates of 75%, 60% and 57% in these three groups, respectively. It is suggested that p53 gene mutations occur frequently at late stage of progression to colorectal adenoma-carcinoma sequence and may relate to its metastasis, while the accumulation of p53 protein may be a specific genetic alteration initiated from adenomatous stage. Thus, the biological significances of the two genetic alterations are different. Investigations of these concomitantly would be helpful in understanding the malignant potential of adenoma and evaluation of its staging.

Objective To investigate the expressions of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) in colonic mucosa of patients with ulcerative colitis (UC)and to analyze the relationship between them. Methods The specimens of colonic mucosa from 32 UC patients were graded according to endoscopic and histological grading standards, and specimens of colonic mucosa from 26 healthy controls were also collected. The expressions of COX-2 and 5-LOX mRNA and protein in colonic mucosa were determined using real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-PCR) and immunohistochemistry. The correlation between COX-2 and 5-LOX was analyzed. Results For UC patients,10 were class 1, 19 class 2 and 3 class 3 according to endoscopic grading, whereas 19 were class Ⅰ , 9 class Ⅱ and 4 class Ⅲ according to histological grading. The expressions of COX-2 and 5-LOX mRNA in active UC patients were 81. 25% and 53.13%, respectively, and were 11.54% and 19. 23% in healthy controls, respectively, with significant differences between the two groups (all P values＜0.01). The positive expressions of COX2 and 5-LOX increased in accordance with increasing of endoscopic grading and histological grading.The levels of COX-2 and 5-LOX were 20. 08±1.17 and 37.83 ±1.48 in colonic mucosa tissues of UC patients, respectively, and 48.42 ± 1.69 and 11.28 ± 1.62 in healthy controls, respectively. There was significant difference between the two groups (all P values＜0.05). A good positive correlation was found between COX-2 and 5-LOX. Conclusions The expressions of COX-2 is closely related to 5-LOX in UC patients. Both may play a pivotal role in inflammation of UC.

Adult ; Humans ; Male ; Recurrent Laryngeal Nerve ; abnormalities

Objective Wnt signal is very important to control the gastrointestinal mucosal proliferation, but its role in the gastric mucosal proliferation after acidified ethanol injury is not clear yet,neither is the relationship with cyclooxygenase 2 (COX-2). Methods X-gal staining was used to measure the expression of Wnt signaling; Western blot and RT-PCR were used to measure the expression of TCF4 and P-Catenin in the gastric mucosa before and after acidified ethanol injury. We also used TOP/flash plasmid to further indentify the relationship between COX-2 and Wnt signal pathway. Results After acidified ethanol injury, the expression of LacZ signal, β-Catenin and TCF4 increased only in the wild type mouse. The expression of β-Catenin and TCF4 protein increased about (3.52 ±0.52) times and (3.02 ±0.62) times separately, and the expression of β-Catenin and TCF4 mRNA increased about (19. 85 ±3.63) times and (17.82 ±4.82) times separately. Without ethanol injury, the expression of TOP/flash plasmid was inhibited by COX-2 inhibitor (NS398) about 80% and promoted by prostaglandin E2(PGE2) about 50%.After 1% ethanol injury, the expression of plasmid was inhibited by NS398 about 25% ; on the contrary,PGE2 promoted the expression about 10%. Conclusion Wnt signal in gastric mucosa is activated after acidified ethanol injury. COX-2 may work through modulating Wnt signal to control the proliferation of gastric mucosa.

Objective To study the expression and the role of interleukin (IL)-23/IL-17 axis in colonic tissue of trinitrobenzene sulphonic acid (TNBS) induced eolitic mice.Methods Mice were divided into four groups:control (n=24),TNBS (n= 24),TNBS 48 hours + mlL-17 antibodies (n=24),TNBS 48 hours + normal rat blood-serum (n= 24).TNBS-induced colitis model was constructed.The mice in control group and TNBS colitis group were sacrificed at 24 hours,48 hours,7th day,respectively.In TNBS 48 hours + mlL-17 antibodies group and TNBS 48 hours + normal rat blood-serum group,a single injection with the polyclonal mlL-17 antibodies or serum were given intraperitoneally at two hours before enema with TNBS,respectively,and the mice were killed at 48 hours after enema with TNBS.The histological score of colon and myeloperoxidase (MPO) activity of colonic tissue were evaluated in each group.IL-23p19 and IL-17 concentrations in colonic tissue were measured by enzyme-linked immunosorbent assay (ELISA).Expression of nuclear factor (NF)-κBp65in colonic tissue was detected by immunohistochemistry method.Expression of IL-23p19,IL-17 and IL-12p35 mRNA in colonic tissue were detected by real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-PCR) with SYBR Green I.Results The protein levels of IL-23p19 in colonic tissue in TNBS colitis groups at 24 hours,48 hours and 7 days were (15.53±3.32),(31.16±4.98) and (14.03±3.56) ng/mg,respectively,and their mRNA level were (4.09±0.34),(3.39±0.46) and (6.54±1.82),respectively.The protein levels of IL-17 were (0.35±0.06),(0.38±0.08),and (0.26±0.05) ng/mg,respectively,and their mRNA level were (4.21±2.61),(2.65±0.91) and (5.63±1.43),respectively.The expression levels of IL-23p19 and IL-17 in colitis model were significantly higher than those in control group and the peak was at 48 hours.Moreover,expression of IL-23p19 and IL-17 and their mRNA were positively correlated to their mRNA levels.In TNBS 48 hours + mIL-17 antibodies group,the expression levels of NF-κBp65,the microscopic scores and MPO (1.86 % ± 0.36 %,0.63 ± 0.52,0.40 ± 0.03 U/g,respectively) were significantly lower than those in TNBS 48 hours group (4.35% ±0.37%,5.13±0.64,2.29±0.40 U/g tissue,respectively).Neutralization of IL-17 was significantly protected against TNBS-induced colonic inflammation and MPO and expression of NF-κB p65.The results indicated that neutralization of IL-17 significantly reduced colonic inflammation and suppressed NF-κBp65 activation.This protection occurred in the presence of equivalent induction of local IL-23 p19 and high levels of IL-12p35 in the polyclonal raiL-17 antibodies-treated mice.Conclusions IL-23/IL-17 axis plays a critical role at the early acute phase of TNBS-induced inflammation.IL-17 may represent a new target for therapeutic intervention for inflammatory bowel disease.