1.Integrin β5 subunit regulates hyperglycemia-induced vascular endothelial cell apoptosis through FoxO1-mediated macroautophagy
Xuze LIN ; Sizhuang HUANG ; Side GAO ; Jinxing LIU ; Jiong TANG ; Mengyue YU
Chinese Medical Journal 2024;137(5):565-576
Background::Hyperglycemia frequently induces apoptosis in endothelial cells and ultimately contributes to microvascular dysfunction in patients with diabetes mellitus (DM). Previous research reported that the expression of integrins as well as their ligands was elevated in the diseased vessels of DM patients. However, the association between integrins and hyperglycemia-induced cell death is still unclear. This research was designed to investigate the role played by integrin subunit β5 (ITGB5) in hyperglycemia-induced endothelial cell apoptosis.Methods::We used leptin receptor knockout (Lepr-KO) ( db/ db) mice as spontaneous diabetes animal model. Selective deletion of ITGB5 in endothelial cell was achieved by injecting vascular targeted adeno-associated virus via tail vein. Besides, we also applied small interfering RNA in vitro to study the mechanism of ITGB5 in regulating high glucose-induced cell apoptosis. Results::ITGB5 and its ligand, fibronectin, were both upregulated after exposure to high glucose in vivo and in vitro. ITGB5 knockdown alleviated hyperglycemia-induced vascular endothelial cell apoptosis and microvascular rarefaction in vivo. In vitro analysis revealed that knockdown of either ITGB5 or fibronectin ameliorated high glucose-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). In addition, knockdown of ITGB5 inhibited fibronectin-induced HUVEC apoptosis, which indicated that the fibronectin-ITGB5 interaction participated in high glucose-induced endothelial cell apoptosis. By using RNA-sequencing technology and bioinformatic analysis, we identified Forkhead Box Protein O1 (FoxO1) as an important downstream target regulated by ITGB5. Moreover, we demonstrated that the excessive macroautophagy induced by high glucose can contribute to HUVEC apoptosis, which was regulated by the ITGB5-FoxO1 axis. Conclusion::The study revealed that high glucose-induced endothelial cell apoptosis was positively regulated by ITGB5, which suggested that ITGB5 could potentially be used to predict and treat DM-related vascular complications.
2.Expression of S100A7A in gastric cancer and its effect on proliferation and metastasis
Wushuang XIAO ; Linjie HONG ; Zhen YU ; Ping YANG ; Jieming ZHANG ; Siyang PENG ; Xiangyang WEI ; Yidong CHEN ; Side LIU ; Jide WANG
The Journal of Practical Medicine 2024;40(10):1344-1350
Objective The objective of this study is to examine the expression level of the S100A7A protein in both gastric cancer tissues and cells,as well as to evaluate its impact on the malignant phenotype of gastric cancer(GC)cells.Methods Immunohistochemical assay was used to detect the expression characteristics of S100A7A in 21 gastric cancer tissues and their corresponding paracancerous tissues,as well as to investigate its correlation with gastric cancer clinicopathological factors.Gastric cancer cells were genetically modified to overex-press S100A7A through plasmid transfection.Subsequently,the impact of S100A7A on the proliferation,migra-tion,and invasion capacities of gastric cancer cells was assessed using cell proliferation assays(EdU assay and plate cloning assay)as well as cell migration and invasion assays(Transwell assay and scratch assay).Results The expression of S100A7A protein was higher in GC tissues than in paracancerous tissues;Overexpression of S100A7A may increase gastric cancer cell proliferation,migration,and invasion.Conclusion S100A7A is a possible oncogene in GC and is predicted to serve as a new diagnostic and therapeutic target for the disease.
3.A meta-analysis of safety and efficacy of endoscopic submucosal tunnel dissection for esophageal submucosal tumors
Qingyuan LI ; Yuyuan XU ; Side LIU
Chinese Journal of Digestive Endoscopy 2018;35(4):270-274
Objective To evaluate the safety and efficacy of endoscopic submucosal tunnel dissection (ESTD) for esophageal submucosal tumors (SMTs). Methods A meta-analysis was performed on 18 related studies of ESTD on the treatment of esophageal SMTs retrieving from Chinese and English databases. Complete resection rate and en bloc resection rate were extracted for efficacy, and the complication rate, recurrence rate and death were used to evaluate safety. Results Complete resection rate was reported in all studies, and the pooled complete resection rate was 97. 5%(95%CI: 95. 4%-98. 6%). There were 9 studies that reported en bloc resection rate, and the pooled en bloc resection rate was 95. 9%(95%CI:90. 1%-98. 3%). Subcutaneous emphysema, mediastinal emphysema, pneumothorax, pneumoper-itoneum and perforation were reported in all 18 studies. The pooled prevalence of air leakage symptoms was 11. 3%(95%CI: 7. 0%-17. 6%) for subcutaneous emphysema and pneumomediastinum, 3. 6%( 95%CI:2. 1%-6. 2%) for pneumothorax and 3. 2%( 95%CI: 1. 9%-5. 4%) for pneumoperitoneum. Additionally, the pooled prevalence of perforation was 4. 9%(95%CI: 3. 1%-7. 8%).Intraoperative bleeding was reported in 2 studies, and the pooled incidence of bleeding was 3. 7%(95%CI: 2. 1%-6. 4%). During the follow-up of the 18 studies, no death was reported, and only 2 cases of recurrence were reported in one study. Conclusion ESTD is safe and effective for esophageal SMTs.
4.Analysis of clinical pathological characteristics and treatment trend in colorectal laterally spreading tumor
Juchang ZHANG ; Xueqing WANG ; Aimin LI ; Side LIU
Chinese Journal of Digestion 2017;37(2):88-93
Objective To explore clinical pathological characteristics and treatment changed with time in patients with colorectal laterally spreading tumors (LST) from 2001 to 2015.Methods The clinical data of 549 patients with colorectal LST who received endoscopic resection or surgical operation between 2001 and 2015 were retrospectively collected.According to the time of diagnosis,patients were divided into 2001 to 2005,2006 to 2010 and 2011 to 2015 groups.The gender,age,lesion size and lesion subtypes,clinical pathologic features and their therapeutic methods were analyzed.Chi-square test was used for statistical analysis.Results The detective rates of colorectal LST in 2001 to 2005 period,2006 to 2010 period and 2011 to 2015 period were 0.38% (50/13 319),(0.60% (144/23 912) and 0.79% (355/ 44 715),respectively,and the differences were statistically significant (x2 =29.34,P < 0.01).During these three period,the male to female ratio was about 1:1,mean age about 59 years old,and the mean maximum diameter of the LST lesions remained about 30 mm.The percentages of granular type laterally spreading tumor (LST-G) in 2001 to 2005 period,2006 to 2010 period and 2011 to 2015 period were 82.4%(42/51),67.7% (105/155) and 78.2%(283/262),respectively;while those of non-granular type laterally spreading tumor (LST-NG) were 17.6 % (9/51),32.3 % (50/155) and 21.8 % (79/362),respectively;and the differences were statistically significant (x2 =7.77,P =0.02).The proportions of LST located at the proximal colon in the three periods were 21.6 % (11/51),34.2 % (53/155) and 41.4 % (150/362),respectively;while the percentages of LST at distal colon were 78.4% (40/51),65.8% (102/ 155) and 58.6 % (212/362),respectively;and the differnces were statistically significant (x2 =8.61,P=0.01).The percentages of high grade neoplasia (HGN) in the three periods were 13.7 % (7/51),21.9 %(34/155) and 48.6%(176/362),respectively;while the percentages of invasive carcinoma were 2.0%(1/51),5.2% (8/155) and 8.3% (30/362),respectively;and the differnces were statistically significantly (x2 =58.89,P<0.01).The percentages of endoscopic mucosal resection (EMR) in the three periods were 56.9%(29/51),58.7% (91/155) and 32.0% (116/362),respectively;the percentages of endoscopic piecemeal mucosal resection (EPMR) were 41.2 % (21/51),23.9 % (37/155) and 14.1% (51/362),respectively;the percentages of endoscopic submucosal dissection (ESD) were 0,12.3% (19/155) and 46.1 % (167/362),respectively;the percentages of surgical operation were 0,5.2 % (8/155) and 7.7 % (28/362),respectively;and the differences were statistically significant (x2 =112.46,P< 0.01).Conclusions From 2001 to 2015,the clinical pathological features and therapeutic methods of colorectal LST changed along with time.The proportion of colorectal LST located at proximal colon increased,and the percentage of LST-G decreased.ESD became the primary treatment,and the proportion of pathological diagnosis of HGN and invasive carcinomas increased after operation.
5.The diagnostic value of endoscopic ultrasound-guided fine needle aspiration for mediastinal and abdominal lymphadenopathy
Jiaying CHEN ; Wen GUO ; Qingyu DING ; Yang LYU ; Wei ZHU ; Yongli YAO ; Fachao ZHI ; Side LIU ; Tianming CHENG
Chinese Journal of Digestive Endoscopy 2017;34(8):568-572
Objective To study the diagnostic value and clinical efficacy of endoscopic ultrasound-guided fine needle aspiration ( EUS-FNA ) for mediastinal and abdominal lymphadenopathy. Methods Thirty patients who underwent EUS-FNA for mediastinal or abdominal lymphadenopathy between May 2009 and December 2015 were reviewed. The clinical efficacy of EUS-FNA was evaluated by pathological results and the follow-up. The EUS-FNA effect on clinical decision was also analyzed. Results Lesions were located in the mediastinum in 10 cases and in the abdomen in 20 cases. The total diagnostic accuracy, sensitivity, specificity, positive predictive value ( PPV) and negative predictive value ( NPV) of EUS-FNA were 96. 7%, 94. 7%, 100. 0%, 100. 0% and 91. 7%, respectively. Of all the 30 cases, 20 lymph glands were of unknown origin. The diagnostic accuracy, sensitivity, specificity, PPV and NPV of EUS-FNA in these lesions were 95. 0%, 88. 9%, 100. 0%, 100. 0% and 91. 7%, respectively. The combination of cytological and histological examination had higher accuracy ( 96. 7% VS 73. 3%, P=0. 026) and sensitivity ( 94. 7%VS 57. 8%, P= 0. 019 ) than cytological examination only. Immunohistochemistry stains were performed in 12 neoplastic cases, and 11 ( 91. 7%) were confirmed. The diagnosis by EUS-FNA had positive impact on clinical decisions in 27 patients ( 90. 0%) . Conclusion EUS-FNA is an effective approach for mediastinal and abdominal lymphadenopathy, and the result has a positive impact on clinical decisions. The combination of cytological and histological examination and application of ancillary techniques, such as immunohistochemistry stains, can improve the diagnostic efficacy of EUS-FNA.
6.Preventive effect of endoclip and endoloop on post-polypectomy bleeding of large colorectal polyps and literature review
Fei WANG ; Qiang ZHANG ; Side LIU ; Huimin DENG ; Huanhuan SUN ; Chuangzhen LIN ; Jiang LIU ; Yang BAI
Chinese Journal of Digestive Endoscopy 2017;34(7):495-501
Objective To investigate the preventive effect of endoclips and endoloops on postpolypectomy bleeding of large colorectal polyps.Methods Data of patients,who underwent polypectomy during January 2013 to March 2016,were retrospectively collected.The diameters of all polyps were more than 10 mm.Cases were divided into 4 groups.Before large pedunculated (with thick stalks) polyps were resected,endoclips were used to ligate the pedicles of polyps in Group A,and endoloops were used in Group B.After large sessile and pedunculated (without thick stalks) polyps were resected,endoclips were used to close the incision of polypectomy in Group C,but not in Group D.The immediate and delayed postpolypectomy bleeding rate and clinicopathologic features were studied.Articles about endoclip or endoloop on preventing post-polypectomy bleeding in PubMed in last five years were searched and analyzed.Results A total of 2 006 polyps were included.The immediate bleeding rate was 3.4% (5/147) and 3.8% (5/132) of Group A and B,respectively.The delayed bleeding rate was 6.1% (9/147) and 7.6% (10/132) of Group A and B,respectively.The delayed bleeding rate of Group C and D was 3.2% (28/888) and 1.9% (16/839),respectively.None of the bleeding cases needed a surgical operation.And no perforation occurred.Six articles were included for analysis.Most of articles revealed that endoclip and endoloop were effective tools in prevention of post-polypectomy bleeding.Conclusion Endoclips and endoloops are useful to prevent bleeding after resection of large pedunculated (with thick stalks) polyps.For large sessile and pedunculated (without thick stalks) polyps (diameter> 10 mm),the effect of endoclips to prevent postpolypectomy bleeding still needs further discussion.
7.Risk factors of pain during colonoscopic examination
Xueying LAI ; Xiaowei TANG ; Silin HUANG ; Wei GONG ; Fachao ZHI ; Side LIU ; Ye CHEN
Journal of Southern Medical University 2017;37(4):482-487
Objective To investigate the risk factorsthat predict pain during colonoscopy for decision of sedation or analgesia before the examination. Methods A total of 283 consecutive patients undergoing colonoscopicexamination at Nanfang Hospital between July, 2016 and September, 2016were retrospectively analyzed. The clinical data and visual analogue scale after the examination were analyzed to identify the risk factors for pain during colonoscopy using univariate analysis and multivariate logistic regression. A risk stratification model for predicting pain in colonoscopy was established. Results The completion rate of the procedure was significantly lower in patients with a visual analogue scale ≥5 (P<0.000). Univariate analysis showed that female patients, previous abdominal surgery, no previous experience with colonoscopy, complaint of abdominal pain before colonoscopy, insufficient experience of the endoscopists, patient's anticipation of high painlevelbefore examination, and a low body mass index (BMI) were all associated with the experience of pain in colonoscopy (P<0.05). Multivariate logistic regressionanalysis identified BMI index (X1), level of experience of the endoscopist (A1, A2, A3) and the patient's anticipation of painlevel (X2) as the risk factors of pain in colonoscopy(P<0.05), and the establishedmodel with the 3 variables was:P=eY/(1+eY),Y=0.049-0.124 × X1-0.97 × X2+1.713 × A1+0.781 × A2+0.147 × A3, which showed a sensitivity of 70.3%and a specificity of 67.5%for predicting pain in colonoscopy. Conclusion The patient's anticipation of a high pain level in colonoscopy, insufficient experience of the endoscopist, and a low BMI are the independent risk factors for pain in colonoscopy, and evaluation of these factors can help in the decision-making concerning the use of sedation or analgesia before colonoscopy.
8.Value of urgent colonoscopy in diagnosis of severe acute lower gastrointestinal bleeding in patients with different bowel cleanliness
Jing LI ; Jin TANG ; Ye CHEN ; Fachao ZHI ; Side LIU ; Meirong HE
Journal of Southern Medical University 2017;37(4):522-527
Objective To investigate the value of urgent colonoscopy in the diagnosis of severe acute lower gastrointestinal bleeding and the optimal bowel preparation before examination. Methods The clinical data were collected from 188 patients undergoing wither urgent or elective colonoscopy for severe acute lower gastrointestinal bleeding in Nanfang Hospital. Univariate analysis was used to assess the effect of the timing of colonoscopy on the diagnostic rate of hemorrhage, and a multivariate model which stratified bowel cleanliness was used to analyze the impact of bowel cleanliness on the diagnostic rate of urgent colonoscopy. Results Of the 188 patients, 118 underwent urgent colonoscopy and 70 underwent elective colonoscopy examinations. The diagnostic rates were comparable between the two groups (44.1% vs 41.4%, P=0.724), but urgent colonoscopy resulted in a significantly higher diagnostic rate for identifying the bleeding source (32.2% vs 18.6%, P=0.041). The proportion of the patients taking oral laxatives was significantly lower in urgent colonoscopy group (P<0.001). Oral laxatives versus enema resulted in good, moderate, and poor bowel cleanliness in 63.6%vs 13.5%, 28.6%vs 24.3%, and 7.8%vs 62.2% of the patients (P<0.001). Univariate analysis indicated that good bowel cleanliness was associated with a significantly higher diagnostic rate of colonoscopy than poor bowel cleanliness (P=0.012). Multivariate analysis showed that with good bowel cleanliness, urgent colonoscopy yielded a significantly higher diagnostic rate than elective colonoscopy (P=0.030);subgroup analyses suggested that good bowel cleanliness improved the diagnostic rate of urgent colonoscopy as compared with poor bowel cleanliness (P=0.015). Conclusion In patients with good bowel cleanliness, urgent colonoscopy yields a higher diagnostic rate than elective colonoscopy for severe acute lower gastrointestinal bleeding. Poor bowel cleanliness resulting from bowel preparation by enema significantly lowers the diagnostic performance of urgent colonoscopy. Oral laxatives are recommended over enemas for bowel preparation before urgent colonoscopy when the patients have stable hemodynamics.
9.Risk factors of pain during colonoscopic examination
Xueying LAI ; Xiaowei TANG ; Silin HUANG ; Wei GONG ; Fachao ZHI ; Side LIU ; Ye CHEN
Journal of Southern Medical University 2017;37(4):482-487
Objective To investigate the risk factorsthat predict pain during colonoscopy for decision of sedation or analgesia before the examination. Methods A total of 283 consecutive patients undergoing colonoscopicexamination at Nanfang Hospital between July, 2016 and September, 2016were retrospectively analyzed. The clinical data and visual analogue scale after the examination were analyzed to identify the risk factors for pain during colonoscopy using univariate analysis and multivariate logistic regression. A risk stratification model for predicting pain in colonoscopy was established. Results The completion rate of the procedure was significantly lower in patients with a visual analogue scale ≥5 (P<0.000). Univariate analysis showed that female patients, previous abdominal surgery, no previous experience with colonoscopy, complaint of abdominal pain before colonoscopy, insufficient experience of the endoscopists, patient's anticipation of high painlevelbefore examination, and a low body mass index (BMI) were all associated with the experience of pain in colonoscopy (P<0.05). Multivariate logistic regressionanalysis identified BMI index (X1), level of experience of the endoscopist (A1, A2, A3) and the patient's anticipation of painlevel (X2) as the risk factors of pain in colonoscopy(P<0.05), and the establishedmodel with the 3 variables was:P=eY/(1+eY),Y=0.049-0.124 × X1-0.97 × X2+1.713 × A1+0.781 × A2+0.147 × A3, which showed a sensitivity of 70.3%and a specificity of 67.5%for predicting pain in colonoscopy. Conclusion The patient's anticipation of a high pain level in colonoscopy, insufficient experience of the endoscopist, and a low BMI are the independent risk factors for pain in colonoscopy, and evaluation of these factors can help in the decision-making concerning the use of sedation or analgesia before colonoscopy.
10.Value of urgent colonoscopy in diagnosis of severe acute lower gastrointestinal bleeding in patients with different bowel cleanliness
Jing LI ; Jin TANG ; Ye CHEN ; Fachao ZHI ; Side LIU ; Meirong HE
Journal of Southern Medical University 2017;37(4):522-527
Objective To investigate the value of urgent colonoscopy in the diagnosis of severe acute lower gastrointestinal bleeding and the optimal bowel preparation before examination. Methods The clinical data were collected from 188 patients undergoing wither urgent or elective colonoscopy for severe acute lower gastrointestinal bleeding in Nanfang Hospital. Univariate analysis was used to assess the effect of the timing of colonoscopy on the diagnostic rate of hemorrhage, and a multivariate model which stratified bowel cleanliness was used to analyze the impact of bowel cleanliness on the diagnostic rate of urgent colonoscopy. Results Of the 188 patients, 118 underwent urgent colonoscopy and 70 underwent elective colonoscopy examinations. The diagnostic rates were comparable between the two groups (44.1% vs 41.4%, P=0.724), but urgent colonoscopy resulted in a significantly higher diagnostic rate for identifying the bleeding source (32.2% vs 18.6%, P=0.041). The proportion of the patients taking oral laxatives was significantly lower in urgent colonoscopy group (P<0.001). Oral laxatives versus enema resulted in good, moderate, and poor bowel cleanliness in 63.6%vs 13.5%, 28.6%vs 24.3%, and 7.8%vs 62.2% of the patients (P<0.001). Univariate analysis indicated that good bowel cleanliness was associated with a significantly higher diagnostic rate of colonoscopy than poor bowel cleanliness (P=0.012). Multivariate analysis showed that with good bowel cleanliness, urgent colonoscopy yielded a significantly higher diagnostic rate than elective colonoscopy (P=0.030);subgroup analyses suggested that good bowel cleanliness improved the diagnostic rate of urgent colonoscopy as compared with poor bowel cleanliness (P=0.015). Conclusion In patients with good bowel cleanliness, urgent colonoscopy yields a higher diagnostic rate than elective colonoscopy for severe acute lower gastrointestinal bleeding. Poor bowel cleanliness resulting from bowel preparation by enema significantly lowers the diagnostic performance of urgent colonoscopy. Oral laxatives are recommended over enemas for bowel preparation before urgent colonoscopy when the patients have stable hemodynamics.

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