Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. However, the molecular mechanisms underlying PDAC are still not completely understood. Circular RNAs (circRNAs) are a unique class of RNA formed by special loop splicing. More and more researchers have paid attention to circRNAs. MATERIAL AND METHODS: In this study, we constructed a circRNA-mediated competing endogenous RNA (ceRNA) network in PDAC. Gene ontology (GO) analysis was performed to explore circRNAs' potential roles in PDAC progression. We also constructed an up-stream transcriptional network of circRNAs' parental genes and found that many transcription factors (TFs), such as tumor protein p53 (TP53) and MYC, could regulate their expression. RESULTS: This study, which aimed to identify differentially expressed circRNAs in PDAC, suggested that circRNAs may also act as biomarkers for PDAC. We analyzed two public datasets (GSE69362 and GSE79634) to identify differentially expressed circRNAs in PDAC. Finally, we found that DExH-Box Helicase 9 (DHX9) may be a potential regulator of circRNA formation in PDAC. Genomic loci of four down-regulated circRNAs - hsa_circ_000691, hsa_circ_0049392, hsa_circ_0005203, and hsa_circ_0001626 - contained DHX9 binding sites, suggesting that they may be directly regulated by DHX9. CONCLUSIONS: Our study identified differentially expressed circRNAs in PDAC, suggesting that circRNAs may also act as biomarkers for PDAC. Additional investigations of function and up-stream regulation of differentially expressed circRNA in PDAC are still needed.

[Re-optimized technology of protective ileostomy with no need of reversal].

OBJECTIVE: To explore the clinical application of aoptimizedtechniquebased onpreviouslyreported protecting stoma with no need forreversal. METHODS: Thetechniquealso used "the assembly of drainage device" to performprotecting ileostomy. The original method includes enterotomy at the terminal ileum to placedrainage device, which was optimized as follows: two intestinal pursestring with 0.5 cm distance were placed 5 cm away from the ileocecal valve. Transverse enterotomy was performed in the anti-mesenteric side. The assembly was placed at the root of the appendix between two pursestring, and then the intestine purse suture was tighten. Ligation of the small intestine anastomosis between the anastomosis ring at both ends was carried out, and theanastomosis ring was deployed. From the root of the appendix in the cecum wall, the assembly was embedded about 2 cm and pulled out of abdominal cavitythough the Trocar hole. RESULTS: Seventeen cases of ultra-low rectal cancer completed protecting stoma, including 11 cases through ileocecal protective stoma. All the anastomosis healed well. Defecation drainage tube was removed 3-5 weeks after anastomosis ring degradation. Drainage nozzle healed after 3 to 5 days, and no complications occurred. CONCLUSION: The optimized ileocecal protective ileostomy has the following advantages: (1)wound healing time is significantly shorter. (2)secondary intestinal fistula can be prevented. (3)no need to fix ileum and less chance of subsequent volvulus, intestinal obstruction.

[Role of integrin α4ß7 in the pathogenesis of ulcerative colitis in rats].

OBJECTIVE: To investigate the role of integrin α4ß7 in the development of ulcerative colitis (UC) in rats. METHODS: Sixty Sprague-Dawley rats were randomly divided into the control group (acetone enema), the model group (2,4-dinitrochlorobenzene, DNCB enema), and the α4 intervention group. Colonic mucosa of different groups was observed and compared in terms of pathology and cytokine changes(IL-2 and IL-6) using ELISA. Semi-quantitative RT-PCR was used to detect the colon α4ß7 expression. Integrin α4ß7(+) lymphocytes in the portal vein of rats were determined by flow cytometry. RESULTS: The expression of α4 mRNA was 0.68±0.24 in the model group and 0.58±0.37 in the intervention group, and the expression of ß7 mRNA was 0.84±0.37 in the model group and 0.65±0.30 in the intervention group, which were all significantly higher as compared to those in the control group(0.15±0.13 for α4 and 0.24±0.62 for ß7, P<0.01). The proportions of integrin α4ß7 positive lymphocytes in the portal vein in the model group and intervention group were significantly higher than that in the control group [(76.7±8.2)% and (68.2±7.6)% vs. (14.7±6.7)%, P<0.01]. The expression of IL-2 and IL-6 and the result of macroscopic and microscopic scores in the intervention group were lower than those in the model group(P<0.05). CONCLUSIONS: High expression of α4ß7 may play an important role in experimental colon mucosa inflammation in rats with ulcerative colitis. The blockade of integrin α4ß7 may be a potential target to reduce colonic mucosa inflammation.

[Role of secondary lymphoid tissue chemokine in the pathogenesis of rat ulcerative colitis].

OBJECTIVE: To investigate the effect of secondary lymphoid tissue chemokine (SLC) on experimental colon lesions in rats with ulcerative colitis. METHODS: Sixty Sprague-Dawley rats were randomly divided into control group, model group and SLC intervention group. Colonic mucosal lesions of different groups were observed with HE staining for inflammation and lymphocyte homing situation. Cytokine IL-2 and IL-6 levels were measured by ABC-ELISA. Semi-quantitative RT-PCR was used to examine the colonic SLC expression. RESULTS: Intestinal inflammation score and colonic cytokine levels were significantly different among three groups (P<0.05, P<0.01). Abnormal lymphocyte homing phenomenon under colonic mucosa was found in the model group and the intervention group. SLC mRNA expression of the model and intervention groups increased significantly compared with the control group (0.846+/-0.047, 0.768+/-0.135 vs 0.312+/-0.112, P<0.01). However, there was no significant difference between model group and intervention group. CONCLUSIONS: SLC may play an important role in experimental colonic mucosal inflammation in rats with ulcerative colitis. Blockade of SLC may be one of effective ways in reducing colonic mucosal inflammation.

[Impact of secondary lymphoid tissue chemokine on lymphocyte migration and the significance thereof in pathogenesis of ulcerative colitis: experiment with rats].

OBJECTIVE: To explore the impact of secondary lymphoid tissue chemokine (SLC) on lymphocyte migration and the significance thereof in the pathogenesis of ulcerative colitis (UC). METHODS: Sixty SD rats were randomly divided into 3 equal groups: model group undergoing dripping of 40% acetone solution of dinitro-chlorobenzene (DNCB) on the back for 2 weeks and then enema of 6% DNCB acetone solution so as to establish models of UC, and then intravenous injection of normal saline (NS) for 5 days; SLC antibody intervention group undergoing intravenous injection of SLC antibody 15 microg x ml(-1) x kg(-1) immediately after the establishing of model; and control group undergoing enema of NS nly and then intravenous injection of NS for 5 days. Six days after the establishing of model venous blood samples were collected from the portal veins of the 3 groups. Lymphocytes were isolated and cultured. RT-PCR was used to detect the mRNA expression of the SLC receptor CCR7. Boyden chamber system was used to examine the migration ability of the lymphocytes exposed to SLC of 20, 40, 60, 80, and 100 ng/ml respectively. ELISA was used to detect the expression of interleukin (IL)-10 and interferon (IFN)-gamma in the supernatants of the lymphocytes of different groups. RESULTS: RT-PCR showed that the CCR7 mRNA expression level of the model group was (0.792 +/- 0.108), significantly higher than that of the intervention group (0.386 +/- 0.115, P = 0.0429), and the CCR7 mRNA expression levels of these 2 groups were both significantly higher than that of the control group (0.106 +/- 0.029, both P < 0.01). SLC dose-dependently promoted the migration ability of the lymphocytes, but there existed a saturation phenomenon. Exposed to 80 ng/ml SLC the migration level of the lymphocytes of the model group peaked to (85.9 +/- 16.0), 3.7 times as high as that of the control group (20.5 +/- 1.8, P < 0.01), and the migration level of the lymphocytes of the intervention group was 38.2 +/- 6.3, significantly higher than that of the control group too (P < 0.05). SLC enhanced the expression of IFN-gamma of the lymphocytes of the model group, while reduced the IL-10 level, and both effects peaked at the concentration of 80 ng/ml (P = 0.042, P = 0.036). CONCLUSION: SLC promotes the lymphocyte migration and boosts the differentiation of lymphocytes, thus participating in the pathogenesis of UC.

Circulating ghrelin in patients with gastric or colorectal cancer.

The purpose of this study was to investigate the pathophysiologic change of ghrelin in gastric and colorectal cancer patients, especially in those with cachexia. Fifty-eight gastric cancer patients, 20 colorectal cancer patients, and 24 healthy control individuals were included in this study. Thirty-one patients were defined as cachectic, based on the percentage of weight loss versus the previous normal weight. The remaining 47 patients were defined as noncachectic. Peripheral hormones, including ghrelin, insulin, leptin, growth hormone, glucagon, and cortisol, and body composition parameters were measured. Plasma ghrelin levels did not increase significantly in cachectic gastric (p = 0.352) or colorectal (p = 0.871) cancer patients as compared with controls and were not correlated with nutrition status and other hormones. The location of gastric cancer (proximal vs. distal) had no influence on ghrelin levels (p = 0.966). These findings suggest that gastric and colorectal cancers may have their special effects on the production of ghrelin. Gastric or colorectal cancer cachexia may be partly due to the lack of increase in ghrelin, which makes exogenous ghrelin therapy feasible in this setting.

[Abnormal lymphocyte homing and colon lesions in ulcerative colitis: experiment with rats].

OBJECTIVE: To investigate the relationship between abnormal lymphocyte homing and colon lesions in ulcerative colitis. METHODS: 60 Sprague-Dawley rats were randomly divided into 3 equal groups: model group [undergoing enema of dinitrochlorobenzene to establish models of ulcerative colitis and then venous injection of normal saline (NS) once a day for 5 days], lymphocyte homing intervention group [undergoing venous injection of secondary lymphoid-tissue chemokine (SLC) antibody, and then venous injection of NS for 5 days], and control group [undergoing venous injection of NS for 5 days]. On the 6th day blood samples were collected from the portal vein to isolated lymphocytes. Distant colon was dissected to undergo pathological examination of submucosal aggregated lymphatic follicles, ulceration, and inflammation, thus observing the lymphocyte homing situation. Specimens of colon mucosa underwent detection cytokine of interleukin (IL)-2 and IL-6. RT-PCR was used to detect the mRNA expression of SLC gene and the chemokine receptor CCR7. The proportion of CCR7 positive lymphocytes which drainage from colonic vein were measured by flow cytometry (FC). RESULTS: Abnormal lymphocyte homing phenomenon under colonic mucosa was found in the model and intervention groups. The relative grey degree of SLC gene mRNA expression of the model and intervention groups were 0.85 +/- 0.05 and 0.77 +/- 0.14 respectively, both significantly higher than that of the control group (0.31 +/- 0.11, both P < 0.01), however, without significant difference between the 2 former groups. The relative grey degree of CCR7 mRNA expression of the model group was 0.79 +/- 0.11, significantly higher than that of the intervention groups (0.39 +/- 0.12, P = 0.0429), and both were significantly higher than that of the control group (0.11 +/- 0.03, both P < 0.01). FC showed that the proportion of CCR7(+) lymphocytes drainage from colonic vein of the model and the intervention groups were 69% +/- 5% and 77% +/- 10% respectively, both significantly higher than that of the control group (17% +/- 84%, both P < 0.01), however, without significant difference between these 2 former groups (P = 0.0837). CONCLUSION: Abnormal lymphocyte homing is associated with inflammation of the colonic mucosa. Blocking of the lymphocyte homing is effective in reducing the inflammation of colonic mucosa.

[Curative effects of basic fibroblast growth factor on anus wound healing].

OBJECTIVE: To observe the curative effects of basic fibroblast growth factor (bFGF) on anus wound healing. METHODS: From April 1996 to December 2000, out of 109 patients with anus trauma, hemorrhoidectomy or fistula resection, 68 were treated with bFGF as the experimental group, while 41 were treated routinely as the control group. The healing of the wound, the general and local reaction were observed. RESULTS: The healing time of the experimental group was(17.00 +/- 1.54) days while that of the control group was(20.00 +/- 1.16) days (P < 0.01). Three weeks after operation, the healing rates of the experimental and control groups were 97.1% and 87.8%, respectively (P < 0.01). No general or local detrimental reactions were found in two groups. CONCLUSION: Local application of bFGF can accelerate the healing of anus wound, and the patients have little pain.