Phosphodiesterases (PDE) are a group of enzymes that can hydrolyze cyclic nucleotides. It is composed of 11 gene related isozyme families (PDE1-PDE11). Due to the diversity of isozymes, PDE distribute in different cells and sub-cells, regulate different intracellular signals and become an important target in intracellular signal pathway. Studies have shown that PDE inhibitor plays an important role in the regulation of gastrointestinal motility and related gastrointestinal diseases. This article reviewed the role and research progress of PDE inhibitor in gastrointestinal tract.

Objective:To investigate the efficacy and safety of different endoscopic treatment strategies for grade Ⅰ-Ⅲ internal hemorrhoids.Methods:Clinical data of 107 internal hemorrhoid patients who received endoscopic sclerotherapy or band ligation in Renmin Hospital of Wuhan University from December 2018 to December 2020 were retrospectively studied. Postoperative adverse events, efficacy, and satisfaction were followed up.Results:Among the 107 patients, there were 45 patients (42.06%) with grade Ⅰ, 55 (52.34%) with grade Ⅱ, and 6 (5.60%) with grade Ⅲ. At the same time, 94.39% (101/107) patients underwent other gastrointestinal endoscopic treatment. The postoperative follow-up time ranged from 3 to 25 months, with a median of 5 months. A total of 84 patients underwent routine endoscopic injection sclerotherapy, and 8 had adverse events after the surgery. The overall effective rate was 97.61% (82/84), and satisfaction rate was 95.24% (80/84). Nine underwent endoscopic foam sclerotherapy, and no postoperative adverse events were observed. The overall effective rate and the satisfaction rate were both 100.00% (9/9). Among the 11 patients undergoing endoscopic band ligation, 2 had adverse events after the surgery. The overall effective rate was 81.82% (9/11), and the satisfaction rate was 72.73% (8/11). Three patients underwent sclerotherapy combined with ligation, and 2 had postoperative adverse events. The overall effective rate was 100.00% (3/3), and the satisfaction rate was 66.67% (2/3). Sclerotherapy was generally superior to ligation in operation cost. Further subgroup analysis for grade Ⅰ-Ⅱ patients showed that for grade Ⅰ patients, sclerotherapy was better than band ligation in the incidence of postoperative pain ( P<0.05), and for grade Ⅱ patients, no statistically significant differences were observed in adverse events, effective rate and satisfaction rate ( P>0.05). Conclusion:Both endoscopic injection sclerotherapy and band ligation for internal hemorrhoids are safe and effective, and may not increase the risk of adverse events when simultaneously completed with other gastrointestinal endoscopic treatment.

Objective:To develop early gastric cancer (EGC) detection system of magnifying blue laser imaging (ME-BLI) model and magnifying narrow-band imaging (ME-NBI) model based on deep convolutional neural network, to compare the performance differences of the two models and to explore the effects of training methods on the accuracy.Methods:The images of benign gastric lesions and EGC under ME-BLI and ME-NBI were respectively collected. A total of five data sets and three test sets were collected. Data set 1 included 2 024 noncancerous lesions and 452 EGC images under ME-BLI. Data set 2 included 2 024 noncancerous lesions and 452 EGC images under ME-NBI. Data set 3 was the combination of data set 1 and 2 (a total of 4 048 noncancerous lesions and 904 EGC images under ME-BLI and ME-NBI). Data set 4: on the basis of data set 2, another 62 noncancerous lesions and 2 305 EGC images under ME-NBI were added (2 086 noncancerous lesions and 2 757 EGC images under ME-NBI). Data set 5: on the basis of data set 3, another 62 noncancerous lesions and 2 305 EGC images under ME-NBI were added(4 110 noncancerous lesions and 3 209 EGC images under ME-NBI and ME-BLI). Test set A included 422 noncancerous lesions and 197 EGC images under ME-BLI. Test set B included 422 noncancerous lesions and 197 EGC images under ME-NBI. Test set C was the combination of test set A and B (844 noncancerous and 394 EGC images under ME-BLI and ME-NBI). Five models were constructed according to these five data sets respectively and their performance was evaluated in the three test sets. Per-lesion video was collected and used to compare the performance of deep convolutional neural network models under ME-BLI and ME-NBI for the detection of EGC in clinical environment, and compared with four senior endoscopy doctors. The primary endpoint was the diagnostic accuracy of EGG, sensitivity and specificity. Chi-square test was used for statistical analysis.Results:The performance of model 1 was the best in test set A with the accuracy, sensitivity and specificity of 76.90% (476/619), 63.96% (126/197) and 82.94% (350/422), respectively. The performance of model 2 was the best in test set B with the accuracy, sensitivity and specificity of 86.75% (537/619), 92.89% (183/197) and 83.89% (354/422), respectively. The performance of model 3 was the best in test set B with the accuracy, sensitivity and specificity of 86.91% (538/619), 84.26% (166/197) and 88.15% (372/422), respectively. The performance of model 4 was the best in test set B with the accuracy, sensitivity and specificity of 85.46% (529/619), 95.43% (188/197) and 80.81% (341/422), respectively. The performance of model 5 was the best in test set B, with the accuracy, sensitivity and specificity of 83.52% (517/619), 96.95% (191/197) and 77.25% (326/422), respectively. In terms of image recognition of EGC, the accuracy of models 2 to 5 was higher than that of model 1, and the differences were statistically significant ( χ2=147.90, 149.67, 134.20 and 115.30, all P<0.01). The sensitivity and specificity of models 2 and 3 were higher than those of model 1, the specificity of model 2 was lower than that of model 3, and the differences were statistically significant ( χ2=131.65, 64.15, 207.60, 262.03 and 96.73, all P < 0.01). The sensitivity of models 4 and 5 was higher than those of models 1 to 3, and the specificity of models 4 and 5 was lower than those of models 1 to 3, and the differences were statistically significant ( χ2=151.16, 165.49, 71.35, 112.47, 132.62, 153.14, 176.93, 74.62, 14.09, 15.47, 6.02 and 5.80, all P<0.05). The results of video test based on lesion showed that the average accuracy of doctors 1 to 4 was 68.16%. And the accuracy of models 1 to 5 was 69.47% (66/95), 69.47% (66/95), 70.53% (67/95), 76.84% (73/95) and 80.00% (76/95), respectively. There were no significant differences in the accuracy among models 1 to 5 and between models 1 to 5 and doctors 1 to 4 (all P>0.05). Conclusions:ME-BLI EGC recognition model based on deep learning has good accuracy, but the diagnostic effecacy is sligntly worse than that of ME-NBI model. The effects of EGC recognition model of ME-NBI combined with ME-BLI is better than that of a single model. A more sensitive ME-NBI model can be obtained by increasing the number of ME-NBI images, especially the images of EGG, but the specificity is worse.

Objective: To investigate the effects of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease. Methods: An in vitro cell model of nonalcoholic fatty liver disease was established using 0.6 mmol/L oleic acid to induce lipid accumulation in HepG2 cells. HepG2 cells were divided into control (Con) group, oleic acid (OA) group, and metformin-low (1mmol/L) and high (10mmol/L) dose group. Oil Red O stain was used to detect intracellular lipid droplet distribution. The levels of alanine aminotransferase and aspartate aminotransferase in the culture supernatant were detected by assay kits. DCFH-DA method was used to detect the reactive oxygen species of HepG2 cells. Double staining flow cytometry was used to detect the apoptosis rate of HepG2 cells. Western blot was used to detect caspase-3, B-lymphocyte lymphoma-related protein, B-cell lymphoma 2, and cytochrome c protein. One-way analysis of variance was used to compare the data between groups. Results: Oleic acid-induced HepG2 cells were significantly increased with lipid droplets. Low and high-dose metformin had reduced intracellular lipid droplets accumulation. The effect of metformin in the high-dose group was more significant than that in the low-dose group. Aspartate aminotransferase and alanine aminotransferase in HepG2 cells of OA group were significantly increased, which were (43.41 ± 7.11) U/L and (29.56 ± 4.11) U/L, respectively. The intracellular aspartate aminotransferase and alanine aminotransferase were decreased significantly after the treatment with low and high-dose metformin, which were (32.44 ± 4.08)U/L, (19.31 ± 3.03) U/L, (26.00 ± 3.11) U/L and (15.11 ± 4.11) U/L, respectively and the differences were statistically significant (P < 0.05). DCFH-DA test results showed that the fluorescence intensity of reactive oxygen species in the oleic acid group was 41.21% ± 4.23%, while the fluorescence intensity of reactive oxygen species in the low and high-dose metformin groups were reduced to 27.44% ± 3.91%, and 17.55% ± 5.11%, respectively and the differences between the groups were statistically significant (P < 0.05). The results of flow cytometry analysis showed that the cell apoptosis rate of the OA group was significantly higher than that of the Con group (12.12% ± 0.72% vs. 3.04% ± 0.57%, P < 0.05).The apoptosis rate of HepG2 cells was significantly reduced after metformin treatment at low and high doses (8.71% ± 0.71%, 5.71% ± 0.61%, P < 0.05). Western blot results showed that compared with the Con group, the expressions of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 were increased in the OA group, while the B-cell lymphoma 2 were decreased (P < 0.05). The expression of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 protein in HepG2 cells was decreased after treatment with low and high-dose metformin, while B-cell lymphoma 2 was increased (P < 0.05). Conclusion Metformin can effectively alleviate steatosis and improve the HepG2 function in cell model of nonalcoholic fatty liver disease. The mechanism of metformin may be related to the reduction of oxidative stress injury, the regulation of protein expression related to mitochondrial apoptosis pathway and the inhibition of cell apoptosis.

Objective To analyze the clinical features of esophageal foreign body(EFB) difficult to remove by gastroscopy.Methods The clinical data of 159 patients with EFBs treated in Renmin Hospital of Wuhan University from January 2013 to April 2017 were analyzed retrospectively.Among 159 cases,the EFBs were removed by gastroscopy in 101 cases(gastroscope group)and removed by non-gastroscope method in 58 cases (non-gastroscope group),including 42 cases removed by esophagoscopy and 16 cases by surgery.The general information of patients,the types of EFB,the condition of impaction,treatments and outcomes of the two groups were analyzed.Results There was no significant difference in age and sex between gastroscope group and non-gastroscope group (P ＞ 0.05).The food typeEFBs included fish bone (n =77),chicken bone (n =45),jujube seeds (n =15),food bolus (n =4);and the non-food type FEBs included spectecleslens (n =2),bottle cap (n =11),denture (n =5).More than one half of FBs were located in the upper esophagus:63.4％ (64/101) in gastroscope group and 66.7％ (28/42) in esophagoscope subgroup;however,EFBs were mostly located in the middle esophagus in surgery subgroup (62.5％,10/16).In gastroscope group and esophagoscope subgroup,the sharp EFBs of length-diameter ＞ 2 cm were rare(n =4,3.9％ and n =3,7.1％),but were common in the surgery group (n =9,56.3％).The EFBs were successfully removed in all patients without massive hemorrhage or death.In gastroscope group (n =101),93 cases had mucosal abrasion and bleeding,5 cases had mild active bleeding,and 1 case had esophageal fistula.In surgical removal (n =16) there were 4 cases of esophageal perforation and postoperative inflammation,3 cases of mediastinal inflammation and 2 cases of mediastinal abscess.Inesophagoscopic removal group (n =42),there were 2 cases of esophageal muscle layer abscess,1 case of esophageal fistula and 1 case of pulmonary infection.Conclusions The most common type of EFBs is of food source.Foreign bodies in the upper and middle segments of the esophagusare difficult to remove with gastroscopy.In case of a sharp foreign body embedded in the middle esophagus,surgical removal is preferred to avoid severe sequences.

Objective To assess the value of double balloon enteroscopy (DBE) in etiological diagnosis of small bowel ulcer.Methods The clinical and endoscopic data of patients undergoing DBE at the Department of Gastroenterology, Renmin Hospital of Wuhan University from January 2010 to January 2016 were reviewed.For patients with small bowel ulcer revealed by DBE, the etiologic diagnosis was retrospectively analyzed.Results One hundred and three patients with small bowel ulcer were included in the analysis.The initial diagnosis based on morphology of ulcer was Crohn's disease (58.3%, 60/103), intestinal tuberculosis (18.4%,19/103), etiology unknown (24.3%, 25/103).The final diagnosis comprehensively based on pathology, clinical data and disease outcome was Crohn's disease (44.7%,46/103), intestinal tuberculosis (18.4%,19/103), lymphoma (3.8%,4/103), eosinophils enteritis (1.9%,2/103), non-steroidal anti-inflammatory drug enteritis (1.9%,2/103), adenocarcinoma (1.0%,1/103), stroma tumor (1.0%,1/103),ischemic enteritis (1.0%,1/103), vascular malformation (1.0%,1/103), Henoch-Schonlein purpura (1.0%,1/103), etiology unknown (24.3,25/103).The accurate diagnosis rate and misdiagnosis rate for Crohn's disease by DBE were 73.3%(44/60)and 10.0%(6/60).The accurate diagnosis rate and misdiagnosis rate for intestinal tuberculosis by DBE were 14/18 and 2/18.Conclusion There are diversity and complexity in etiologic diagnosis of small bowel ulcer.The diagnosis should be based on the comprehensive analysis of morphology of ulcer, endoscopic and surgical pathology and clinical data.Follow up of small bowel ulcer by DBE may provide important information for etiologic diagnosis.

Objective To investigate the role of microRNA-490-5p (miR-490-5p) in the regulation of visceral sensitivity in rats with intestinal dysfunction.Methods The lentivirus vector system was used to construct the rno-miRNA-490-5p lentivirus expression vector.The rats were divided into normal group,diarrhea-predominant irritable bowel syndrome (IBS-D) group,lentivirus empty vector group and the siRNA silent group and the latter three groups were model groups.The efficiency of siRNA was measured by real-time polymerase chain reaction (PCR).The rats were gavaged with 10％ India ink,and then the time of first black stool,water content of feces and threshold of expansion capacity caused abdominal elevation or back arching were calculated.The visceral sensitivity of rats after miRNA-490-5p silenced was evaluated with abdominal withdrawal reflex (AWR) score by stimulating with different intensities of colonic dilatation.The abdominal electrical activity of rats stimulated by colonic distension was measured by BL-420F biological and functional experimental system.The change of the tension of rats isolated colon intestinal stimulated with acetylcholine chloride was also detected by BL-420F biological and functional experimental system.T test was used to compare the differences between the model groups and the normal group.One way analysis of variance was performed for multi-group comparison after miRNA-490-5p interfered.For comparison between two groups among multiple groups,least significant difference (LSD) method was used when the variance was equal,and Games-Howell method was used when the variance was unequal.Results The gastrointestinal propulsion time and the threshold of expansion capacity caused abdominal elevation or back arching of model groups were both lower than those of the normal group ((8.54±4.07) hvs (12.33±2.23) h,(0.56±0.08) mL vs (0.84±0.09) mL),and the differences were statistically significant (t =2.62 and 6.37,both P ＜ 0.05).After distension with 0.8 mL and 1.2 mL sodium chloride solution,the AWR scores of model groups were significantly higher than those of the normal group (3.20±0.56 vs 1.20±0.45,3.73±0.46 vs 2.60±0.55),and the differences were statistically significant (t=7.20 and 4.58,both P＜0.01).There was no significant difference in AWR score between the model groups and the normal group when distended with 1.6 mL sodium chloride solution (3.93 ±0.26 vs 3.80 ± 0.45) (P＞0.05).After miRNA-490-5p silenced,gastrointestinal propulsion time of normal group,IBS-D group,lentivirus empty vector group and the siRNA silent group was (11.12±1.01) h,(6.23±3.17) h,(6.09 ± 2.26) h and (12.36±1.97) h,and the differences among four groups were statistically significant (F=10.55,P＜0.01).The abdominal electrical activity of normal group,IBS-D group,lentivirus empty vector group and the siRNA silent group distension stimulated with 0.8 mL and 1.2 mL sodium chloride solution was (64.91 ± 10.50),(101.79 ±11.73),(80.49±1.27),(66.92±3.24) μV,and (105.09±52.40),(131.71± 16.74),(111.00±6.41) and (95.49± 4.2) μV,and the differences among four groups were statistically significant (F=16.82 and 9.14,both P＜0.05).There was no significant difference in abdominal electrical activity amplitude between silenced group and normal group ((66.92±3.24) μV vs (64.91±10.49) μV and (95.49±4.22) μV vs (105.09±2.40) μV) (all P＞ 0.05).After distension with 1.6 mL sodium chloride solution,the abdominal electrical activity amplitudeof silenced group was lower than the other groups,and the differences were statistically significant (F=11.09,P＜0.01).After adding 1∶1 000 acetylcholine chloride added,the tension of colon of normal group,IBS-D group,lentivirus empty vector group and the siRNA silent group increased by 0.71 ± 0.21,0.81±0.06,0.88±0.21 and 0.43±0.07,however there was no significant difference among the four groups (F=2.57,P =0.100).Conclusions Visceral hypersensitivity existed in rats with intestinal dysfunction.miRNA-490-5p may be involved in the regulation of visceral sensitivity.

Objective To investigate the differences in eNOS gene expression,activity and its metabolites before and after human bone marrow mesenchymal stem cells (hBMSCs) are induced into vascular endothelial cells.Methods hBMSCs were induced into vascular endothelial cells.The morphological changes of the cells were observed under inverted microscope.Transwell assay was used to detect the cells' migration ability.The protein expression of eNOS was detected by immunofluorescence and Western blot.The activity of eNOS was detected by ELISA and the content of NO in cell culture supernatant was determined by nitrate reduction method.Results Compared with those in the undifferentiated group,the morphological changes of the differentiated cells were obvious.Cell migration ability increased by 238.10％ (73.000±7.002 vs.21.000±4.359,P＜0.05).The expression of eNOS protein increased by 114.72％ (0.423±0.011 vs.0.197±0.079,P＜0.05).The activity of eNOS was enhanced by 157.49％ (4.967±0.073 vs.1.929±±0.103,P＜0.05).The synthesis and release of NO increased by 155.67％ (184.909±1.853 vs.72.323±0.426,P＜0.05).Conclusion After hBMSCs are induced into endothelial cells,the expression of eNOS gene increases,their activities increase,synthesis and release of the metabolite NO increase.It may provide a basis for prevention and treatment of cardiovascular diseases with stem cells.

Intestinal microbes play a vital role in the development of colorectal diseases.Fusobacterium nucleatum (Fn), an commensal resident in the human gut, is closely associated with colorectal diseases, and attracted widespread attention.Studies have found that Fn may contribute to the development and prognosis of inflammation and colorectal cancer.This article reviews the research advances of the relationship between Fn and the development of colorectal diseases.

Objective To investigate the feasibility and application value of total enteroscopy with double balloon enteroscopy(DBE)for diagnosis and treatment of patients with obscure gastrointestinal bleeding(OGIB). Methods The clinical and endoscopic data of patients underwent DBE for OGIB in the Department of Gastroenterology,Remin Hospital of Wuhan University from January 2010 to December 2015 were retrospectively analyzed. Results Total enteroscopy was indicated in 36.3%(136/375)of patients. The success rate was 86.0%(117/136)and complication rate was 1.5%(2/136). Negative findings,non-small bowel lesions and small bowel lesions were detected in 44.4%(52/117), 6.8%(8/117), and 48.7%(57/117)of patients with total enteroscopy. Re-bleeding occurred in 8.9%(4/45)of patients with negative total enteroscopy,while 1 small bowel mesenchymoma and 1 gastric fundus Dieulafoy′s lesion were revealed subsequently. Re-bleeding occurred in 33.3%(5/15)of patients with incomplete enteroscopy,and 1 small bowel polyp and 1 small bowel angiectasis were revealed subsequently. Conclusion DBE can complete total enteroscopy within one day and provide important clinical information of OGIB. Non-small bowel lesions,small bowel lesion missed by DBE and potential bleeding lesions in small bowel beyond the reach of DBE should be considered in patients with negative enteroscopy.