Establishment and validation of symptomatic patients colorectal screening score for predicting colorectal neoplasia risk.

OBJECTIVES: Currently, most colorectal neoplasia (CRN) screening strategies target asymptomatic individuals. However, studies on patients with non-specific gastrointestinal symptoms (NSGS) are limited. We aimed to develop a CRN risk score specifically for patients with NSGS. METHODS: We prospectively enrolled patients who underwent initial colonoscopy between June 2020 and June 2021. A new risk scoring system was constructed and its applicability was evaluated. RESULTS: A total of 1522 consecutive patients were enrolled, among whom 1016 symptomatic patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The constructed Symptomatic Patients Colorectal Screening (SPCS) score showed higher diagnostic efficacy and sensitivity than several previous scoring systems. Using the SPCS score, the patients were divided into a low-risk group (-2 to 3 points) and a high-risk group (4-10 points) for CRN. Additionally, the detection rate of CRN in the training and validation cohorts of the high-risk group were 41.7% and 37.0%, respectively. The SPCS score detected 79.3% (188/237) of CRN and 87.5% (42/48) of advanced CRN in the high-risk group, which reduced the workload of colonoscopy to 45.9% (466/1016). CONCLUSION: An effective CRN risk scoring system was established and validated for symptomatic patients, which accurately classified individuals into low-risk and high-risk groups for CRN and might be used to optimize colonoscopic resource allocation.

miR­31 promotes tumorigenesis in ulcerative colitis­associated neoplasia via downregulation of SATB2.

Ulcerative colitis (UC) features chronic, non-infectious inflammation of the colon. The risk of ulcerative colitis­associated neoplasia (UCAN) increases in direct association with the duration of this disease. Whether miRNAs exert a regulatory effect on the pathogenesis of UCAN has remained to be elucidated. In the present study, differentially expressed genes (DEGs) and microRNAs (miRNAs/miRs) were identified using bioinformatics analysis of Gene Expression Omnibus datasets. Enrichment analyses were performed to determine the function of the DEGs. The target genes of key miRNAs were predicted using miRWalk. Validation of DEGs and miRNAs in patients with UC, UC with low­grade dysplasia and UC with high­grade dysplasia (UC­HGD) was performed using reverse transcription­quantitative PCR analysis. A total of 38 differentially expressed miRNAs and 307 mRNAs were identified from the profiles and miR­31 was validated as being overexpressed in UCAN tissues, particularly in the UC­HGD samples. Furthermore, special AT­rich DNA­binding protein 2 (SATB2) was validated as a target gene of miR­31 and SATB2 expression was negatively correlated with miR­31 expression. Therefore, miR­31 is upregulated in UCAN and it may promote tumorigenesis through downregulation of SATB2.

Reevaluation of a rightward shift in colorectal cancer: A single-center retrospective study in Tianjin.

OBJECTIVES: Some Western reports have shown a proximal shift in colorectal cancer (CRC), but there are few studies in China. This study aimed to provide more information for the management and screening of CRC by investigating trends in the anatomic distribution of CRC among the Chinese population in recent years. METHODS: A retrospective study was conducted on patients with CRC admitted to the Digestive Endoscopy Center of Tianjin Medical University General Hospital between January 2000 and December 2017. Patients were divided into a left-sided colorectal cancer (LSCRC) group and a right-sided colon cancer (RSCC) group. The detection rates of LSCRC and RSCC based on patients' age and sex, and on the time periods were analyzed. RESULTS: A total of 2319 cases were diagnosed with CRC among 75 183 consecutive patients. The prevalence of CRC showed a significant reduction from 2000-2008 to 2009-2017 (3.8% vs 2.7%, P < .001). The proportion of RSCC presented a downtrend from 2000-2008 to 2009-2017 (40.6% vs 37.7%, P > .05). There were slightly more RSCCs in female patients than in male patients, with no significant difference (40.9% vs 36.5%, P > .05). The proportion of RSCC in patients aged ≥50 years was similar to that in younger patients. The alarming symptoms between LSCRC and RSCC showed a significant difference (P < .05). CONCLUSIONS: In the present study, the prevalence of CRC declined significantly with time. However, there did not appear to be a rightward shift in CRC among the patients in Tianjin over the past 18 years.

Hemostatic effect of topical hemocoagulase spray in digestive endoscopy.

AIM: To evaluate the hemostatic effect of topical hemocoagulase spray in digestive endoscopy. METHODS: Eighty-nine patients who developed oozing bleeding during endoscopic treatment from September 2014 to October 2014 at Center for Digestive Endoscopy, Tianjin Medical University General Hospital were randomly divided into either a study group (n = 39) or a control group (n = 50). The study group was given topical hemocoagulase spray intraoperatively, while the control group was given traditional 8% norepinephrine spray. Hemostatic efficacy was compared between the two groups. Bleeding site, wound cleanliness and perforation were recorded, and the rates of perforation and late bleeding were compared. RESULTS: Successful hemostasis was achieved in 39 (100%) patients of the study group and in 47 (94.0%) patients of the control group, and there was no significant difference in the rate of successful hemostasis between the two groups. Compared with the control group, after topical hemocoagulase spray in the study group, the surgical field was clearer, the bleeding site was more easily identified, and the wound was cleaner. There was no significant difference in the rate of perforation between the study and control groups (16.7% vs 35.0%, P = 0.477), but the rates of late bleeding (0% vs 15.8%, P = 0.048) and overall complications (P = 0.032) were significantly lower in the study group. CONCLUSION: Topical hemocoagulase spray has a definite hemostatic effect for oozing bleeding in digestive endoscopy, and this method is convenient, safe, and reliable. It is expected to become a new method for endoscopic hemostasis.

IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice.

AIM: To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells (MSCs) in inflammatory bowel disease (IBD). METHODS: The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis (UC) was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium (DSS) for 8 days to induce colitis. Before DSS treatment, the mice were injected with MSCs, MSC-eGFP or MSC-IL37b. Their body weight was measured each day, and the colons and spleens were harvested on d 10 for pathological and biochemical analyses. RESULTS: In biopsied specimens of the patients with active UC, the expression of IL-37 was dramatically elevated in inflamed mucosa, mainly in epithelial cells and infiltrating immune cells. Compared to MSC-eGFP or MSCs, MSC-IL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-IL37b administration increased the percentage of myeloid-derived suppressor cells (MDSCs) among total splenic mononuclear cells as well as the percentage of regulatory T cells (Tregs) among splenic CD4+ T cells in the mice. Moreover, MSC-IL37b administration increased the IL-2+ cells and decreased the IFN-γ+ cells among splenic CD4+ T cells. CONCLUSION: IL-37 is involved in the pathophysiology of UC. IL-37b gene transfer enhances the therapeutic efficacy of MSCs in DSS-induced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.

[DNA methylation of microRNA-34b/c and microRNA-124a in gastric cancer].

OBJECTIVE: To explore the effects of DNA methylation of microRNA (miRNA) gene on their expressions in patients with gastric carcinoma. METHODS: A total of 80 subjects were divided into gastric carcinoma group (n = 40) and control group (n = 40). The DNA methylation status of miRNA-34b/c and miRNA-124a gene promoters was detected by DNA methylation specific polymerase chain reaction (MSP) in gastric carcinoma tissues and normal mucosal tissues. RESULTS: The positive rate of DNA methylation of miRNA-34b/c gene promoter was 77.5% (31/40) and 5.0% (2/40) in gastric carcinoma and control groups respectively. There was statistically significant difference between two groups (P < 0.05). The positive rate of DNA methylation of miRNA-124a gene promoter was 60.0% (24/40) and 0 in these two groups respectively. There was statistically significant difference between two groups (P < 0.05). Also the hypermethylation positivity of gene promoter of miRNAs was correlated with the clinicopathological features of gastric carcinoma. CONCLUSION: The hypermethylation of miRNA-34b/c and miRNA-124a gene promoters may play a crucial role in the occurrence and development of gastric carcinoma.

[Correlation of E-cadherin hypermethylation to tumorigenesis and development of gastric cancer].

BACKGROUND & OBJECTIVE: CpG island hypermethylation in promoter region of E-cadherin (E-cad) gene plays an important role in tumorigenesis of many tumors. This study was to explore the correlation of E-cadherin hypermethylation to tumorigenesis and development of gastric cancer. METHODS: Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation of E-cad gene in 41 specimens of gastric cancer, 40 specimens of premalignant gastric lesions and 38 specimens of normal gastric tissues. The expression of E-cad protein was detected by SP immunohistochemistry. RESULTS: The positive rate of E-cad gene methylation was significantly higher in gastric cancer than in premalignant lesions and normal tissues (19.5% vs. 2.5% and 0.0%, P<0.05). The positive rate of E-cad protein was significantly lower in gastric cancer tissues than in premalignant lesions and normal tissues (70.7% vs. 97.5% and 100.0%, P<0.05). The positive rate of E-cad gene methylation was significantly higher in poorly differentiated cancer tissues than in well differentiated cancer tissues (43.8% vs. 4.0%, P<0.05), significantly higher in gastric cancer tissues with lymph node metastasis than in those without lymph node metastasis (33.3% vs. 5.0%, P<0.05), and significantly higher in gastric cancer tissues with serosa invasion than in those without serosa invasion (35.0% vs. 4.8%, P<0.05). The positive rate of E-cad protein was significantly lower in gastric cancer tissues with E-cad gene methylation than in those without E-cad gene methylation (0.0% vs. 87.9%, P<0.05). CONCLUSION: CpG island hypermethylation of E-cad gene exists in gastric cancer, which down-regulates E-cad expression and might be involved in tumorigenesis and development of gastric cancer.

[A study of interleukin-10 gene polymorphism in irritable bowel syndrome].

OBJECTIVE: To investigate whether three diallelic polymorphisms at the position -1082, -819 and -592 in the promoter region of the IL-10 gene were associated with diarrhea-predominant irritable bowel syndrome (D-IBS). METHODS: The IL-10 gene -1082, -819 and -592 position polymorphisms were genotyped by amplification refractory mutation systems-polymerase chain reaction (ARMS-PCR) methods in 43 patients with D-IBS and 41 healthy subjects (HS). RESULTS: Compared with HS, D-IBS patients had a greater frequency of T/T genotype at IL-10 gene promoter -819 position (67.4% vs 39.0%, P < 0.05), the frequencies of -819 C/T and C/C genotype were not significantly different (23.3% vs 43.9% and 9.3% vs 17.1%, P > 0.05). D-IBS patients also had a greater frequency of -592 A/A genotype compared with HS (67.4% vs 39.0%, P < 0.05), the frequencies of -592 C/A and C/C genotype were not significantly different (23.3% vs 43.9% and 9.3% vs 17.1%, P > 0.05). No significant difference was found in genotype at IL-10 gene promoter -1082 position. The -819 T allele frequency in D-IBS was significantly higher than that in control (79.1% vs 61.0%, P < 0.05), whereas -819 C allele frequency in D-IBS was lower (20.9% vs 39.0%, P < 0.05). D-IBS patients also had a greater frequency of -592 A allele compared with HS (79.1% vs 61.0%, P < 0.05), -592 C allele frequency in D-IBS was lower (20.9% vs 39.0%, P < 0.05). No significant difference was found in -1082 G or A allele frequency. CONCLUSIONS: The presence of -819 T/T and -592 A/A genotype may be related to development of D-IBS.

[Differential expression of motility-related protein-1/CD9 gene in gastric cancers and premalignant lesions].

OBJECTIVE: To clone and identify gastric cancer-related genes and explore the possible pathogenic mechanism of gastric cancer. METHODS: The differentially expressed cDNA bands were isolated by fluorescent mRNA differential display in gastric cancer specimens, matched normal gastric mucosa and premalignant lesions. The motility-related protein-1 (MRP-1/CD9) gene was one of the down-regulated genes. MRP-1/CD9 gene expression in different kinds of gastric tissue was analyzed by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: MRP-1/CD9 expression was down-regulated in all gastric cancer tissues. Northern blot analysis confirmed this differential expression. RT-PCR analysis showed that the MRP-1/CD9 gene expression was much lower in gastric cancers(0.31+/-0.18) than in the matched normal gastric tissue (0.49+/-0.24) and in the premalignant lesions (0.47+/-0.18) (P<0.05), and its expression in intestinal type gastric cancer (0.38+/-0.16) was higher than that in diffuse type gastric cancer (0.22+/-0.17) (P<0.05). CONCLUSION: The MRP-1/CD9 gene expression was down-regulated in gastric cancer, its expression was probably related to the carcinogenesis and histology types of gastric cancer.

[Serotonin transporter gene polymorphism in irritable bowel syndrome].

OBJECTIVE: To investigate the association of serotonin transporter (SERT) gene polymorphism with irritable bowel syndrome (IBS). METHODS: The VNTRs and 5-HTTLPR polymorphism of SERT gene was assessed with polymerase chain reaction in 81 patients with IBS and 48 healthy subjects(HS). RESULTS: Compared with HS, IBS patients have a greater frequency of STin2.12/10 genotype in VNTRs region and a smaller frequency of STin2.12/12 genotype, however no significant difference was found in polymorphism of this region among the patients with C-IBS, D-IBS and A-IBS. We also found that the 5-HTTLPR allele L/L genotype occurred with greater frequency in C-IBS patients than in other two subgroups, whereas the L/S genotype occurred with smaller frequency in C-IBS. The frequency of association between 12/12 genotype and L/L genotype (12/12-L/L) in C-IBS was significantly higher than those in A-IBS and HS. CONCLUSIONS: The presence of STin2.12/10 genotype may be correlated with IBS. The presence of L/L genotype and 12/12-L/L genotype association in IBS patients carries an increased risk of C-IBS, whereas the presence of the L/S genotype carries an increased risk of D-IBS and A-IBS.

[Study of genes related to gastric cancer and its premalignant lesions with fluorescent differential display].

BACKGROUND & OBJECTIVE: It is generally recognized that development of gastric cancer arises gradually from premalignant lesions (chronic atrophic gastritis, intestinal metaplasia and dysplasia). Differential display of mRNA is a valuable tool for the identification of differentially expressed genes in human carcinogenesis and development. The search for differentially expressed genes in gastric cancer and its premalignant lesions may help to define molecular alterations in the gastric mucosa tissue that may precede the development of gastric cancer. METHODS: The differentially expressed cDNA bands were isolated and identified by fluorescent differential display in 2 gastric cancer, 2 premalignant lesions, and 2 normal gastric mucosa tissues and then reamplified by PCR. After being cloned, all cDNA fragments were sequenced. Through BLAST software, the sequencing results were compared with GenBank database for homology analysis. Expression of SPTAN1 in 7 gastric cancer tissues, 7 premalignant lesions, and 7 normal gastric mucosa tissues were identified by RT-PCR. RESULTS: Four differentially expressed cDNA fragments were found. Three of them were over-expressed in the gastric cancer tissue. One of them was over-expressed in premalignant lesions and normal gastric mucosa tissue. One cDNA fragment over-expressed in gastric cancer was homologous to SPTAN1 and its over-expression in gastric cancer was confirmed by RT-PCR. The other three cDNA fragments showed significant homology to known gene sequences in GenBank but their functions are unknown. CONCLUSION: Three of the four differentially expressed genes over-expressed in gastric cancer. SPTAN1gene was significantly higher in gastric cancer tissue than in normal gastric mucosa tissue and dysplasia tissue.