Objective To analyze clinical characteristics of gastroesophageal reflux disease(GERD) in aged patients for improvement of diagnosis and treatemcnt. Methods The reflux disease questionnaire was performed in patients diagnosed as GERD based on Montreal definition and classification as well as Rome Ⅲ criteria.All patients were divided into elderly group (≥65 years) and control group(＜65 years). The incidence of hita[ hernia (HH), the frequencies of esophagitis (based on Los Angeles classification), clinical features, and quality of life were compared between two groups. Results There was no difference between two groups in male/female ratio and morbidity of HH(P＞0.05). In comparison with control group, the frequency of esophagitis graded as LC or LD increased and extra-esophageal symptoms were higher in elderly group (P＜ 0.05), but the lower typical symptoms (heartburn and regurgitation) were seen in the elderly group(P＜0.05). The scores of role physical, bodily pain and role emotional were higher in elderly group than those in control group (P＜0.05). There was no significant differences between two groups in physical function, vitality,social functioning, mental health, and general health. Conclusion The elderly GERD patients often have lower score of typical reflux symptoms (heartburn and regurgitation) and high incidence of severer esophagitis, but their quality of life is not significantly influenced.

Objective To assess whether the G870A polymorphism of cyclin D1 (CCND1)was associated with individual susceptibility to gastric cancer in China. Methods Case-control study of 214 individuals was conducted, including 108 controls (non ulcerative dyspepsia) and 106 cases of gastric cancer. The polymorphism analysis of CCND1 A/G was performed in blood samples by PCR-RFLP method. Results The frequency of GG genotype was 19.8% and 7.4% in patients with gastric cancer and controls, respectively. The risk for gastric cancer in patients homozygous (GG) for CCND1 genotypes was 3.5 times higher in comparison with patients carrying AA genotypes (P＜0.05, OR =0.281). Furthermore, the stratification analyses showed that the male, elderly (≥60 years) or H. pylori infected gastric cancer patients who carrying GG genotype were more susceptible to gastric cancer compared with those carrying AA or GA genotype. Conclusion GG genotype is associated with increased susceptibility to gastric cancer in high risk area of Xi'an.

Objective To investigate the impacts of S-ademetionine (SAM) on cell cycles,apoptosis and invasive capacity of gastric cancer cell lines,and its effects on methylation and expressions of c-myc and uPA.Methods MKN-28,SGC-7901 and MKN-45 cells were treated with gradient concentrations of SAM(0,2 and 4 mmol/L) for 72 hours.The changes of cell cycles and apoptosis were detected by flow eytometry,and invasion was detected by transwell assay.The expressions and methylations of c-myc and uPA were examined by RT-PCR and MSP,respectively.Results The cell apoptosis significantly increased and cell invasive capacity was restrained in three cell lines with increase of SAM concentration (all P values<0.01).In SGC-7901,the cell percentage of G0/G1 phase significantly increased [(74.53±2.49)% vs.(56.67±1.18)%,P<0.053,whereas the cell proliferation index (PI) decreased [(25.50±2.46)% vs.(43.33±1.18)%,P<0.05] in comparison with controls.The expressions of c-myc and uPA mRNA in SGC-7901,uPA mRNA in MKN-45 and in 4 mmol/L SAM treated MKN-28 significantly decreased.The methylations of c-myc gene in SGC-7901 and uPA gene in three cell lines were reversed after treated with SAM.Conclusions SAM reduces expressions of c-myc and uPA by reversing the methylations of c-myc in SGC-7901 and uPA in all three cell lines.However SAM,as methyl donor,can restrain the development and progression of tumor when hypomethylation widely presents in cancer.

Objective To study the effects of extracellular-signal regulated kinase mitogenactivated protein kinase (ERK-MAPK) signaling pathway inhibition on histone phosphorylation and the related gene expression in human colorectal cancer cells.Methods Two human colorectal cancer cell lines (SW1116 and HCT116) were cultured and treated with gradient(0,20,40/μmol/L) doses of ERK-MAPK signaling pathway inhibitor U0126.Cell viability was determined by cell counting kit 8 (CCK-8) assay.Cell cycle distribution was assessed by flow cytometry.The expression levels of histone H3 kinases including ribosomal S6 serine-threonine kinase (RSK-2) and mitogen-and stressactivated protein kinase 1 and 2 (MSK1 and MSK2),and the levels of histone H3 (Ser10) phosphorylation and c-Fos protein were detected using Western blotting.Results Treatment of these two human colorectal cancer cell lines with ERK-MAPK inhibitor resulted in a time and dose-dependent inhibition of cell proliferation significantly. Proliferation rate of HCT116 was reduced to 47% at 72 hours after 40/μmol/L U0126 treatment. Cell cycle analysis showed that the percentage of phase G0/G1 cells significantly increased (P<0. 01) and the percentage of phase S cells decreased (P<0.01) after treatment with ERK-MAPK inhibitor. The expression of MSK1 and RSK2 reduced obviously in both of human colorectal cancer cell lines treated with U0126, which resulted in a 28% and 40% reduction of levels of MSK1 and RSK2 as compared with control HCT116 cells respectively,while no detectable change in the expression of MSK2 was found. Consistent with this, the expression level of histone H3 (ser10) phosphorylation was markedly down-regulated by ERK-MAPK inhibitor, and the related protein c-Fos expression decreased accordantly. Conclusions Decreased ERK-MAPK signaling pathway may reduce histone H3 (Ser10) phosphorylation via suppression of the activity of histone H3 kinase including MSK1 and RSK2, but not MSK2, consequently decrease the expression of c-Fos protein, which results in the inhibition of colorectal cancer cells proliferation.

Objective To evaluate association of plasma levels of homocysteine, folate and vitamin B12 as well as genetic polymorphisms of homocysteine with ulcerative colitis (UC). Methods Three hundred and ten consecutive patients with UC and 936 healthy controls were recruited.Polymorphisms of methylenetetrahyrdofolate reductase (MTHFR, C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G were genotyped using PCR-RELP methods. Eighty eight patients and one hundred healthy controls were randomly selected for determination of plasma levels of homocysteine by enzymatic cycling assay, and concentrations of folate and vitamin B12 were measured by corpuscle immune chemiluminescence assay. Results The variant allele and genotype frequencies of MTHFR 1298C, MTR 2756G and MTRR 66G were significantly higher in UC patients than in the healthy controls (P＜0. 01). Moreover, plasma homocysteine level was obviously higher in UC patients than in controls [(21.73±6.59) mmol/L vs(12.47±5.01)mmol/L,P<0.01).Whereas both folate F(11.25±6.19)nmol/L] and vitamin B12 [(322.81±128.47)pmol/L] concentrations were significantly lower in UC patients than in controls [(15.28±7.72)nmol/L and (422.59±129.36)pmol/L,respectively,P<0.01].Logistic analysis revealed that abnormal levels of homocysteine,folate and vitamin B12 were independent risk factors for UC(P<0.01).Conclusions Plasma levels of homocysteine,folate and vitamin B12 as well as the related genetic polymorphisms of homocystein are correlated with UC,which provides a theoretical basis for supplement of folate and vitamin B12 in treatment of UC patients.

Objective To investigate clinical value of endoscopic ultrasonography (EUS) on diagnosis and treatment of esophageal leiomyoma.Methods The clinical feature of patients diagnosed as esophageal leiomyoma by EUS was analyzed.All patients underwent conventional gastroscopy and EUS examination as well as blood test.The EUS findings were compared with histopatholoical diagnosis for endoscopically or surgically resected specimens.All patients were followed-up with EUS for 14.3 months (range 2-36 months) for leiomyoma recurrence.Results A total of 191 patients were diagnosed with esophageal leiomyomas by EUS.Clinical manifestation,serum examination,conventional gastroscopy and spiral CT were not helpful for diagnosing esophageal leiomyoma,One hundred and sixteen patients with esophageal leiomyomas were treated by either endoscopic resection (111 cases) or surgical excision (5 cases).of which,101 resected specimens were pathologically confirmed as leiomyomas.The diagnostic accuracy of EUS was 87%.The follow-up study showed that there was no change of leiomyomas in 75 untreated patients and no recurrence was found in 116 surgically treated patients.Conclusion Esophageal leiomyoma is a benign tumor,EUS plays a very important role in diagnosis and treatment of this disease.

Objective To investigate the differentiation of neuroendocrine component (NEC) in colorectal adenocarcinoma in relation to its significance by comparing the outcome between patients with or without NEC.Methods The paraffin sections from patients with pathologically confirmed colorectal adenocarcinoma were retrospectively collected and screened for those with NEC by morphological examination and immunohistochemistry with neuroendocrine markers.Control patients (n=54) without NEC were selected from colorectal cancer database and 2: 1 matched on the basis of clinical features with NEC positive patients (n=27).Relative analysis was performed between two groups.Results With a median follow-up of 72 months,the 5-year disease free survival was 58.0% (16/27) in NEC positive group and 79.1% (43/54) in control group (P=0.036).Similarly,the 5-year cancer-specific overall survival was significantly lower in NEC positive group than in control group (58.3% versus 81.1%,P=0.037).Cox regression showed that the 5-year cumulative risks of disease recurrence and cancer-caused death in NEC positive patients were 2.38 and 2.41 times higher than those in control patients,respectively.Conclusions NEC appears to bear a poor prognosis in patients with colorectal adenocarcinoma.

Objective To estimate the effect and the intracellular signal transduction pathway of insulin-like growth factor I (IGF-I) on the expression of stem cell factor(SCF) in colonic smooth-muscle cells(SMC). Methods The SMCs isolated from colon of the SD rats by enzymolysis were cultured and identified by α-actin immunocytochemical method. Colonic SMCs were cultured either with 100 μg/L of IGF-I at different time points (0, 8, 16, 24 and 48 hours) or with different concentrations (0,5,10,50,100 and 150 μg/L) of IGF-I for 16 hours. The expressions of SCF in colonic SMCs pretreated with or without speicific phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor LY-294002 or mitogen-activated protein (MAP) kinase (MEK1) inhibitor PD-98059 were examined by Western blotting and quantitative reverse transeription-polymerase chain reaction and immunofluorescence. Results Low expression of SCF was found in colonic SMCs cultured in the bovine serum free medium. There was no effect of 5 or 10 μg/L of IGF- I on the expression of SCF. However, the expressions of SCF mRNA and protein were increased when stimulated with high concentrations (50,100,150 μg/L) of IGF-I. The peak expression of SCF was showed at the 16th hour after stimulating with 100 μg/L of IGF- I that was considered as the most effective concentration in vitro. The expression of SCF was not influenced by LY-294002, but was partly blocked by PD-98059. Conclusions The expression of SCF in colon SMCs may be induced by IGF-Ⅰ through MAP kinase signaling pathway.

Objective To investigate the prevalence and the risk factors of gastroduodenal damages induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Methods One hundred and eighty-four patients who were prescribed NSA1Ds for long time in rheumatology and cardiovascular clinics were enrolled. Clinical data such as age, sex, medication history and body mass index were recorded. The lesions were estimated by endoscopy and the specimens were tested for Helicobacter pylori (H. pylori) infection. Results Peptic ulcer was found in 63 (34. 24%) patients including gastric ulcer in 22, duodenal ulcer in 34 and compound ulcer in 7. The endoscopic examination showed that 57 out of 121 patients without peptic ulcer had ≥3 erosive lesions. Logistic regression analysis revealed that H. pylori infection was important risk factor that induced the peptic ulcer in those who were taking NSAIDs for long time (OR = 13. 86, 95% CI: 6. 53 ～ 29. 43). The incidence of gastroduodenal damage was similar in patients taking NSAIDs and low dose aspirin (OR =0.45,95CI:0.16～ 1.28). Conclusions NSAIDs may cause gastroduodenal damages in long-term users and H. pylori infection was an important risk factor. The effect of low dose aspirin on gastroduodenal damages is as same as NSAIDs.

Objective To evaluate the efficacy and safety of two kinds of dosage of 5-aminosalicylic acid zinc enteric-coated capsule in treatment of active ulcerative colitis (UC). Methods The muhicentre, double blind, dosage reaction and contrast trial was conducted in six hospitals during March 2004 to Sep. 2004. One hundred and eight patients with UC were randomly allocated into the high dosage (n= 36, 1 g, bid) and the low dosage (n = 36, 0.5 g, bid) of 5-aminosalicylic acid zinc enteric-coated capsule groups, and the Olsalazine sodium group (n = 36, 1 g, tid) with a 8-week treatment. The efficacy and adverse events of 5-aminosalicylic acid zinc enteric-coated capsule were evaluated based on the clinical presentations and endoscopic findings. Results The clinical efficacy was 68.97% in high dosage group, 45. 45% in low dosage group and 62.86% in Olsalazine sodium group with no significant difference (P>0. 05). The endoscopic examination showed that the healing rate of UC in high dosage group and low dosage group was 51.72% and 21.21%, respectively, whereas the efficacy rate was 82.76% and 69.70% respectively. The results showed that high dosage was more effective than low dosage (P=0.023), but was similar to Olsalazine sodium (healing rate of 34.29% and effective rate of 88.57% ,P>0. 05). Diarrhea was main adverse event, which was accounted for 2.8% (1/36) in high dosage group and 2.8% (1/36) in the Olsalazine sodium group. There was no adverse event in low dosage group. Conclusions 5-aminosalicylic acid zinc enteric-coated capsule is an effective agent in treatment of UC, especially in high dosage. It is similar to Olsalazine sodium in treatment of UC, and has advantages in reducing medication times.