Background CUEDC2, a CUE domain-containing protein, is highly expressed in many tumors, which also may be associated with inflammation. Aims In this study, we studied whether CUEDC2 plays a role in the progress of inflammatory bowel disease using CUEDC2 knockout (KO) mice and discussed the effects of CUEDC2 on cell proliferation in colonic mucosa. Methods CUEDC2 KO mice were administered with drinking dextran sodium sulfate (DSS) to establish colitis mice model. At different time points after DSS administration, body weight and stool consistency of mice were graded. Cytokines in colon tissue such as IL-6 were measured by RT-PCR. NF-κB and STAT3 signaling pathways in colon tissue were assessed by western blotting. Besides, cell proliferation of intestinal mucosa was analyzed by immunohistochemical staining. Results CUEDC2 alleviated the colonic inflammation, showing elevated body weight loss, worse diarrhea, and more severe colonic mucosal injury in CUEDC2 KO mice than WT mice. Moreover, pro-inflammatory cytokines such as IL-6, TNFα, COX2, and MIP2 were significantly elevated. In CUEDC2 KO mice, the NF-κB and STAT3 signaling pathways were increasingly activated in different stages of progression of the colonic inflammation, and the percentage of proliferating cells as indicated by Ki67, CyclinD1, and BrdU in the inflammatory tissues was significantly increased. Conclusions Our findings demonstrate that CUEDC2 plays an important role in protection from colonic inflammation, primarily by inhibiting the NF-κB and STAT3 signaling pathways and preventing excessive proliferation of the inflammatory epithelial cell.

Objective To analyze the differences in the clinical characteristics,endoscopy,pathology and therapy between the patients with new onset ulcerative colitis(UC)in the elderly versus youth and middle-aged patients.Methods A review analysis was carried out in the 178hospitalized patients with UC in Third Hospital of Peking University from 1994 to 2010.The patients were divided into two groups according to the age of onset:UC onset at age of 60 years and older were enrolled in elderly

[目的]探讨美沙拉嗪肠溶片(惠迪)对溃疡性结肠炎(UC)患者血清中乳腺癌相关肽(TFF1)、肠三叶因子(TFF3)表达的影响及其临床意义.[方法]在本院治疗的UC患者132例,随机分为研究组67例和对照组65例.对照组服用柳氮磺胺吡啶(SASP)1.0g,4次/日,治疗疗程4周,病情缓解后改为1.0g,2次/日,继续服用4周.研究组患者服用惠迪1.0g,3次/日；疗程8周.测定比较两组治疗前后血清TFF1和TFF3的水平.[结果]与治疗前比较,两组患者血清TFF1和TFF3均明显增加,且差异有显著性(P＜0.05).同对照组相比,治疗组血清TFF1和TFF3水平增加更为显著,两组间相比差异有显著性(P＜0.05).[结论]上调血清TFF1、TFF3水平可能为惠迪治疗溃疡性结肠炎的一个作用机制,其上调作用要优于SASP.

OBJECTIVE:To evaluate the relationship between serum lipid level and colorectal adenoma.METHODS:A review analysis was carried out of the patients who underwent colonoscopy in Peking University Third Hospital from May 2009 to February 2010. Subjects with history of colorectal adenocarcinoma before colorectal surgery or of medication which had influenced the serum lipid level were excluded. Adenoma group included the patients who had colorectal adenoma which was evidenced by pathology. The patients with no adenoma were ascribed to control group. The serum total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol levels of the two groups were analyzed. The relation between serum lipid level and location of colorectal adenoma was also summarized.RESULTS:A total of 227 patients were included for final analysis, of whom 124 were in adenoma group (77 males and 47 females; mean age: 56.5±10.7 years )and 103 in control group(53 males and 50 females; mean age: 56.8±13.6 years). Serum triglyceride level in adenoma group [(1.83±1.04) mmol/L] was significantly higher than that of control group[(1.54±0.86) mmol/L(P=0.022)] and HDL-C level in adenoma group[(1.05±0.32) mmol / L] was significantly lower than that of control group [(1.26±0.46) mmol/L(P=0.000)]. In adenoma group, 73 cases were with HDL-C decreased, which was significantly higher than that of control group (44 cases, P=0.015). In addition, higher incidence of proximal colonic adenomas was observed in elevated triglycerides group and low HDL-C group (39.8%, 37.4%), compared with control group (25.5%), but there was no statistical difference between the two groups(P=0.358).CONCLUSION:The findings of this study suggest that dyslipidemia may affect the incidence of colorectal adenoma, particularly hypertriglyceridemia and low HDL-C levels. In addition, higher triglyceride and lower HDL-C levels seem to be related to higher incidence of proximal colonic adenomas.

AIM: To observe the progression of proliferation and apoptosis of colorectal preneoplastic sequence,and to explore the potential role of abnormal expression pattern of PPAR-γ and β-catenin in the preneoplastic sequence.METHODS: Colorectal ACFs and adenomas were induced using a modified DMH-induced carcinogenesis method in SD rats. The expression patterns of PPAR-γ and β-catenin in colorectal preneoplastic sequence were detected using immumohistochemisty. Proliferation and apoptosis of preneoplastic sequence were analyzed using Ki-67 and Bcl-2.RESULTS: In the "Normal-ACF-Adenoma" sequence induced by DMH,abnormal expression of Ki-67 occurred at the transformation stage of "Normal-ACF". Positive nucleuses of Ki-67 distributed extensively within the aberrant crypt,differing from normal crypt significantly and similar to adenoma. Abnormally high expression of Bcl-2 appeared until ACF transformed to adenoma,presenting broad positive granules in the cytoplasm. PPAR-γ,as Ki-67 did,abnormally expressed during the "Normal-ACF" shift with extensive distribution of positive nucleuses. Β-catenin,as Bcl-2 did,presented with different positive location and density until the transformation of "ACF-Adenoma" with evident positive nucleuses.CONCLUSION: In the stage of "Normal-ACF",the main abnormality is higher proliferation rate found in aberrant crypt than normal crypt,and this change might be correlated to abnormal expression of PPAR-γ. Depression of apoptosis became obvious in the stage of "ACF-Adenoma",and the elevated expression of β-catenin and Bcl-2 might have a synergic role in the formation of adenoma.

OBJECTIVE To understand whether peroxisome proliferators-activated receptor-gamma (PPAR-gamma) plays an important role in the chemopreventive effect of sulindac on precancerous lesions (aberrant crypt foci, ACF) of rats. METHODS Male Sprague-Dawley rats were used in this study and raised in Special Pathogen Free room. Sulindac was the main research object. Carcinogenic agent, 1, 2-dimethylhydrazine (DMH), was used to induce colonic precancerous lesions. Pioglitazone was chosen as agonist of PPAR-gamma and GW9662 used as a specific complete antagonist of PPAR-gamma. ACFs were induced according to the protocol certified in prior experiments. There were 7 groups, named as Negative control group, DMH group, Sulindac group, Sulindac+GW9662 group, Pioglitazone group, Pioglitazone+GW9662 group and GW9662 group. The experiment period was 12 weeks. At the end of the experiment, all rats were sacrificed by euthanasia. Half of the colon including the rectum was taken and immersed in formalin at 4 degrees Celsius overnight, and then recorded the number and size of ACF with the help of anatomic microscope stained by methylene blue. RESULTS (1) Sulindac and agonist of PPAR-gamma could significantly inhibit DMH-induced ACFs of rats from 137.8+/-59.4 to 73.9+/-32.1 and 96.4+/-32.6 with a decrease of 45.7% (P<0.01) and 30.0%(P<0.05) compared with DMH group. Antagonist of PPAR-gamma could counteract the chemopreventive effect of sulindac with an increase from 73.9+/-32.1 to 106.3+/-33.9; (2) The expression of PPAR-gamma in colorectal mucosa increased significantly during the DMH induction period compared with negative control group, the relative values of gray were 0.304+/-0.288 and 2.292+/-1.380 (P<0.01), sulindac and pioglitazone could decrease the expression of PPAR-gamma remarkably compared with DMH group, the relative values of gray were 1.023+/-1.115 and 0.352+/-0.187 (P<0.01), and the application of GW9662, antagonist of PPAR-gamma could promote the expression of PPAR-gamma in some degree, and the relative values of gray were 1.279+/-0.303 and 0.998+/-0.295 (P>0.05). CONCLUSION The expression of PPAR-gamma had risen in DMH-induced ACFs of rats significantly. Sulindac and agonist of PPAR-Gamma (pioglitazone) could inhibit the formation of ACF, and followed by a decrease of PPAR-gamma. Antagonist of PPAR-gamma could interfere with the effect of sulindac. PPAR-gamma might play an important role in the chemopreventive effect of sulindac on colorectal pre-cancerous lesions of rats and activation of PPAR-gamma pathway could inhibit the initiation and evolvement of ACF induced by DMH.

Objective To evaluate the long-term effect of sulindac in attempting to maintain the regression of colorectal adenomas and changing of pathology of familial adenomatous polyposis (FAP) patients. Methods FAP patients who were diagnosed by family history and colonscopy were treated with sulindac 400mg per day. The patients received colonoscopy examination regularly to assess number of polyps. Biopsies of remnant polyps were obtained. The type and dysplasia grade of biopsies were evaluated and compared with baseline.Results Eighteen patients of FAP received sulindac. The average age was (37.4±9.8) years old. The average period of treatment was (65.3±31.6) months. Compared with baseline, the average number of polyps reduced significantly at last follow-up (P<0.01). There were totally 200 adenoma biopsies obtained before the treatment. Among them, 86.5% were tubular, while 13.0% were tubulovillous adenoma and 0.5% was villous adenoma. The dysplasia of grade Ⅰ, Ⅱ and Ⅲ were 40.0%, 43.5% and 11.5%, respectively. After sulindac treatment, there were totaly 133 adenoma biopsies obtained. 97.7% of adenoma biopsies were tubular adenoma, while 2.3% were tubulovillous adenoma. There was significant difference compared with baseline (P<0.01). The dysplasia of grade Ⅰ, Ⅱ and Ⅲ were 48.9%, 48.1% and 3.0% respectively, which had significant difference with baseline (P<0.01). However, 1 patient who took sulindac 100 mg/d by himself developed colonic cancer. Conclusion Long-term use of sulindac seems to be effective in maintaining the regression of colorectal adenoma of FAP patients and reducing dysplasia grade and tubulovillous adenoma of retained colorectal adenoma. These effects are associated with dosage. However, the effect of sulindac to regress the adenoma seems to be uncompleted. FAP patients who take sulindac need to receive colonoscopy regularly to find colorectal cancer.

OBJECTIVE:To compare effects of sulindac, PPARgamma activator and PPARgamma antagonist on the proliferation and apoptosis of the colonic cancer cells, and to investigate whether sulindac exerts its colonic neoplasm inhibiting activity through pathway of PPARgamma.METHODS:Cell strain HT-29 of colonic cancer was divided into six groups: the control group, sulindac group, 15d-PGJ2 (PPARgamma activator) group, GW9662 (PPARgamma antagonist) group, sulindac+GW9662 group and 15d-PGJ2+ GW9662 group. After 24 and 48 hours' culturing, proliferation status of each group was determined by immunocytochemical staining of PCNA, and cell apoptosis status was determined by double staining method of AnnexinV-FITC/PI, examined on flow cytometer.RESULTS:(1) Proliferation status of the colonic cancer cells of each group: 24 and 48 hours after medication, PCNA positive ratios were 33.2%+/- 4.5% and 25.0%+/-4.7% of the control group, 11.8%+/-3.7% and 8.6%+/-1.9% of sulindac group, 11.2%+/-2.5% and 11.4%+/-2.1% of 15d-PGJ2 group, 35.3%+/-4.3% and 26.8%+/-3.9% of GW9662 group, 16.5%+/-5.3% and 12.2 %+/-2.4% of sulindac + GW9662 group, 21.0%+/-4.8% and 21.5%+/-4.2% of 15d-PGJ2+GW9662 group. (2) Apoptosis ratio of colonic cancer cells of each group: 24 hours after medication, apoptosis rate of colonic cancer cells was 13.0%+/-1.0% of the control group, 41.0%+/-2.6% of sulindac group, 11.5%+/-0.6% of 15d-PGJ2 group, 12.4%+/-0.9% of GW9662 group,33.6%+/-2.3% of sulindac+GW9662 group, and 13.0%+/-1.0% of 15d-PGJ2 + GW9662 group. 48 hours after medication, apoptosis rate was 14.0%+/-3.4% of the control group, 95.3%+/-1.5% of sulindac group, 31.5%+/-2.3% of 15d-PGJ2 group, 13.0%+/-1.9% of GW9662 group, 86.8%+/-0.4% of sulindac+GW9662 group, and 12.9%+/-1.0% of 15d-PGJ2+GW9662 group.CONCLUSION:Both sulindac and PPARgamma activator can inhibit proliferation and promote apoptosis of colonic cancer cells, and their effects can be antagonized by PPARgamma antagonist, which indicates that as a kind of PPARgamma ligand, sulindac can inhibit proliferation of colonic cancer cells via activating PPARgamma.

Objective To discuss the indication,technique,effect,and safety of colonoscopic resection of colorectal submucosal tumor(SMT).Methods A total of 33 patients with SMT,which was diagnosed colonoscopically and pathologically,were treated by endoscopy.The sizes of the tumors were 0.2-2.2 cm in diameter,and 0.2-1.2 cm in the diameter of the roots.After injecting adequate adrenalin saline deeply into the root of SMT,the mass of those,who had negative nonlifting sign,was attracted,snared,and then cut using high frequency electrotome.In 7 cases of smaller SMT,the tumor was gripped.Results No perforation,large amount of hemorrhage,or burns of the colorectal wall was found.Complete resection was achieved(no tumor tissue was detected on the edge or bottom of the SMTs after endoscopic resection,or pathological examination found no tumor tissue after open surgery) in 29 cases,including 18 carcinoids,6 leiomyomas,2 hamartomas,2 lipomas,and 1 neurofibroma.Except 3 patients with leiomyoma were lost,26 of the patients were followed up for a median of 44.5 months(3 months to 12 years and 7 months).No recurrence was found during the follow-up.The 4 carcinoids were resected partially(there were tumor tissues remained on the edge or bottom of the SMTs after endoscopic resection,or the pathological examination after open surgery showed tumors).Two of the 4 were transferred to open surgery(one was followed up for 2 years and 3 months,the other was lost).The other two patients refused operation and received a followed-up of 5 months and 2 years and 4 month respectively.None of the 4 patients had recurrence during follow-up.Conclusions Colonoscopic treatment can be applied to the patients with SMT sized ≤1.2 cm at the root and negative nonlifting sign.The method is safe,effective,and minimal invasion.Pathological examination is recommended after the colonoscopic resection,open surgery is necessary for the partially resected SMTs.

NSAIDs是结、直肠肿瘤的预防性药物,但不能完全阻止腺瘤和肿瘤的发展.将NSAIDs和针对特殊细胞信号通路且低毒的其他药物联合用于癌及癌前病变的化学预防成为目前研究热点,现综述如下:

OBJECTIVES:To study the changes of duodenal ulcer, gastric ulcer, gastric cancer and Helicobacter pylori (Hp) infectious status, according to the clinical data of endoscopy in our hospital during the past 25 years. METHODS:The patients with duodenal ulcer, gastric ulcer and gastric cancer diagnosed by endoscopy and pathology had been selected, 104 987 general endoscope cases during the period from Jan. 1980 to Dec. 2004. The general cases were divided into 8 age groups as follows: 10-< 20 years old, 20-< 30 years old, 30-< 40 years old, 40-< 50 years old, 50-< 60 years old, 60-< 70 years old, 70-< 80 years old and > or = 80 years old. RESULTS:The average detected rate of duodenal ulcer, gastric ulcer, and gastric cancer are 13.03%, 4.19% and 1.68% respectively. The detected rate of gastric ulcer was decreased after 1996. The detected rate of duodenal ulcer was decreased after 1999. The gastric cancer detected rate fluctuate between 1.02% and 2.36%. The average ages of duodenal ulcer, gastric ulcer and gastric cancer are 41.8, 50.7 and 59.4 respectively. The tendency of average age shows ascendant. In all patients, the detected rate of Hp showed slightly descendent after 1999. CONCLUSIONS:The diagnostic age of duodenal ulcer, gastric ulcer and gastric cancer shows ascendant tendency; The detected rates of duodenal ulcer, gastric ulcer show descendent tendency; There is no apparent change in the detected rate of gastric cancer. The Hp detected rate shows descendent tendency slightly.

近年来发现肝硬化门脉高压患者除食管、胃底静脉曲张破裂出血以外,上消化道大出血的另一个主要原因是由于门脉高压所致的胃粘膜损伤引起的.

cases of ALD are analyzed clinically. 80 cases of viral posthepatitic cirrhosis are matched controls, we analyze the epidemiology, clinical situation, laboratory test, related factors of AC(alcoholic cirrhosis) and the effect of drug to protect liver after temperance. ALD patients hospitalized are all male, the majority of them is AC. The peak of episode is in the youth and the middle-age(35-55years old). The infectious rate of hepatitis virus of ALD is 16.44% which is higher than that of the general. There is no completely positive correlation between the occurrence of AC and amount for liquor taken daily and the time limit of drinking. The infection of hepatitis virus aggravates the liver lesion of AC and is the risk factor for AC develope to hepatocarcinoma. The clinical situation of ALD has no specificity, but liver tumefaction is more common in AC than in viral posthepatitic cirrhosis. The serum levels of enzyme (AST、ALT、GGT)are above normality, and the step-up of GGT take advantage. After temperance, the effect of drug to protect liver in AC is better than in viral posthepatitic cirrhosis.

为了解肝硬化患者血清、腹水中瘦素水平情况,探讨其可能的临床意义.选择肝硬化组、对照组各21例,分别测定受试者的血脂、肝功、血糖、胰岛素、血清瘦素及部分腹水瘦素水平,测量其身高、体重,计算体重指数、体脂肪含量.瘦素、胰岛素分别采酶联免疫吸附试验、放射性免疫试验方法测定,胰岛素抵抗用HOMA模式估算.结果显示:肝硬化、对照组的血清瘦素水平差异不显著,且肝硬化组无性别差异.肝硬化患者的血清瘦素水平与体重指数(BMI)、总蛋白、总胆固醇、空腹胰岛素相关,与胰岛素抵抗(IR)无关.腹水中的瘦素水平与腹水的性质有关,渗出液高于漏出液.上述结果说明肝硬化患者血清瘦素水平表现异常,与疾病本身相关.

酒精性肝病(ALD)是西方国家青、中年死亡的主要原因之一.一般认为,日饮酒(80～150)克,连续5年以上即可致肝损伤,可引起酒精性脂肪肝(AFL)、酒精性肝炎(AH)及酒精性肝硬化(AC).