1.TCN1 Deficiency Inhibits the Malignancy of Colorectal Cancer Cells by Regulating the ITGB4 Pathway
Xinqiang ZHU ; Xuetong JIANG ; Qinglin ZHANG ; Hailong HUANG ; Xiaohong SHI ; Daorong HOU ; Chungen XING
Gut and Liver 2023;17(3):412-429
Background/Aims:
This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC).
Methods:
We studied the biological function of TCN1 by performing gain-of-function and loss-offunction analyses in HCT116 cell lines; examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells; and determined potential molecular mechanisms using HCT116 and SW480 CRC lines and mouse xenotransplantation models. Tumor xenograft and colonization assays were performed to detect the tumorigenicity and metastatic foci of cells in vivo.
Results:
TCN1 knockdown attenuated CRC cell proliferation and invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism analyses showed that TCN1 interacted with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1 knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A. Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/plectin complex, leading to cytoskeletal damage.
Conclusions
TCN1 might play an oncogenic role in CRC by regulating the ITGB4 signaling pathway.
2.Application status and progress of intraoperative nerve monitoring in pelvic autonomic nerve preserving radical resection of rectal cancer
Wanqing CUI ; Qiongxiang HU ; Fei ZHANG ; Chungen XING ; Yongyou WU ; Kui ZHAO
Chinese Journal of Gastrointestinal Surgery 2023;26(12):1202-1209
The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.
3.Application status and progress of intraoperative nerve monitoring in pelvic autonomic nerve preserving radical resection of rectal cancer
Wanqing CUI ; Qiongxiang HU ; Fei ZHANG ; Chungen XING ; Yongyou WU ; Kui ZHAO
Chinese Journal of Gastrointestinal Surgery 2023;26(12):1202-1209
The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.
4.Rapamycin affects radiosensitivity of colorectal cancer by activating the autophagy of M2 macrophage
Lening SHAO ; Baosong ZHU ; Xiaodong YANG ; Jianping CAO ; Chungen XING
Chinese Journal of Radiological Medicine and Protection 2022;42(9):657-663
Objective:To investigate the effects of rapamycin on the autophagy activation of M2 macrophages and the radiosensitivity in colorectal cancer xenograft.Methods:THP-1 cells were induced into Type-Ⅱ macrophages with PMA and/or IL-4. Rapamycin and Bafilomycin A1 were uesd to activate and suppress autophagy of M2 macrophage, respectively. Colorectal cancer LoVo cells were inoculated on BALB/c-nu/nu nude mice. After the xenograft tumor size approached to 10 mm in diameter, the nude mice were divided into the following groups randomly: M2 macrophage autophagy inactive group and active group, autophagy downregulation of the activated group, and nontreatment control group. The tumors in mice were irradiated with 8 Gy X-rays in two fractions, and the radiosensitivity of colorectal cancer xenograft in each group was analyzed.Results:The expression levels of M2 macrophage markers Arg-1 and CCL-22 were significantly higher than those in M0 macrophage. The tumor weight, volume [(1.93±0.05)g, (2.14±0.06)cm 3] and micro-vessel density (36.37±1.04) in M2 autophagy inactive group were higher than those in control group [(1.35±0.05)g, (1.77±0.02)cm 3, 25.69±1.34] ( t=20.07, 14.56, 10.92, P < 0.05). After activation of M2 autophagy, the tumor weight, volume and micro-vessel density were significantly decreased to (0.89±0.03)g, (1.24±0.01)cm 3, and 13.60±1.52 ( t=44.37, 40.32, 21.43, P < 0.05). After down-regulation of M2 autophagy with bafilomycin A1, the tumor weight, volume and micro-vessel density were increased to (1.02±0.07)g, (1.37±0.02)cm 3, and 21.06±1.41 ( t=4.67, 13.79, 6.23, P < 0.05). Autophagy inaction suppressed the expression of Livin and Survivin in tumor ( t=2.64, 7.90, P < 0.05), and the activation of M2 autophagy further down-regulated the expression of Livin, Survivin ( t=5.43, 9.39, P < 0.05). The expression levels of Livin and Survivin were increased after the treatment with bafilomycin A1 ( t=2.80, 3.17, P<0.05). Conclusions:M2 macrophagy promoted the growth of colorectal cancer xenograft by inducing the formation of micro-vessels in the tumor, which is one of the mechanisms of tumor-associated macrophages participating in the radiotherapy resistance of colorectal cancer. Activation of M2 autophagy by rapamycin inhibited the ability of M2 macrophagy in promoting tumor growth, and induced apoptosis of colorectal cancer cells after radiotherapy by down-regulating the expression of anti-apoptotic genes Livin and Survivin, thus increased the radiosensitivity of colorectal cancer.
5.Clinical Comparison of Proximal Gastrectomy With Double-Tract Reconstruction Versus Total Gastrectomy With Roux-en-Y Anastomosis for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction
Xiaoming MA ; Mingzuo ZHAO ; Jian WANG ; Haixing PAN ; Jianqiang WU ; Chungen XING
Journal of Gastric Cancer 2022;22(3):220-234
Purpose:
The incidence of adenocarcinoma of the esophagogastric junction (AEG) has increased in recent years, and the optimal surgical strategy for AEG remains highly controversial. We aimed to evaluate the safety and efficacy of proximal gastrectomy with double-tract reconstruction (PG-DT) for the treatment of patients with AEG.
Materials and Methods:
We retrospectively analyzed patients with Siewert type II/III AEG between January 2013 and July 2018. Clinicopathological characteristics, survival, surgical outcomes, quality of life (QOL), and nutritional status were compared between the PG-DT and total gastrectomy with Roux-en-Y anastomosis (TG-RY) groups.
Results:
After propensity score matching, 33 patients in each group were analyzed. There were no statistical differences between the 2 groups in terms of disease-free survival and overall survival. The surgical option was not an independent prognostic factor based on the multivariate analysis. In addition, no differences were found in terms of surgical complications. There were no significant differences in QOL assessed by the Visick grade, Gastrointestinal Symptom Rating Scale, or endoscopic findings. Furthermore, the long-term nutritional advantage of the PG-DT group was significantly greater than that of the TG-RY group.
Conclusions
PG-DT is a safe and effective procedure for patients with local Siewert type II/III AEG, regardless of the TNM stage.
6.The analysis of peripheral blood T lymphocyte subsets in patients with colorectal cancer : a single center cross-section study
Tixian XIAO ; Guannan ZHANG ; Zhifeng QIU ; Chungen XING ; Taisheng LI
Chinese Journal of Internal Medicine 2019;58(6):453-455
The distribution of peripheral blood lymphocyte subsets were compared between patients with colorectal cancer and healthy controls.The number of natural killer(NK) cells and CD8+T cells and the percentage of naive CD4+T cells were all decreased significantly in patients.On the contrary,the percentages of memory CD4+T cells,HLA-DR+ CD8+ T cells and CD38+ CD8+ T cells were significantly increased.It suggests that the tumor killing effect of cytotoxic lymphocytes in peripheral blood is impaired in patients with colorectal cancer,whereas the immune response is over stimulated.
7.Comparative study of clinical efficacy between video-assisted anal fistula treatment and traditional fistula resection plus seton in treatment of complex anal fistula.
Li ZHENG ; Jinyan LU ; Yuwei PU ; Chungen XING ; Kui ZHAO
Chinese Journal of Gastrointestinal Surgery 2018;21(7):793-797
OBJECTIVETo explore the efficacy of video-assisted anal fistula treatment (VAAFT) in treatment of complex anal fistula.
METHODSClinical data of 87 patients with complex anal fistula undergoing operation at Department of General Surgery, the Second Affiliated Hospital of Suzhou University from September 2015 to December 2016 were collected to conduct a cohort study. The operative procedure depended on economic conditions and patient preference. Patients were divided into VAAFT group (42 cases) and traditional fistula resection plus seton (FRS) group (45 cases). The procedure of FRS was to completely remove the fistula along external wall, the inner opening and surrounding scar tissues, then, the inner opening was closed with absorbable suture. For deeper and more complex fistula, the above procedure should be combined with seton. Based on the concept of endoscopic minimally invasive surgery, VAAFT could deal with the fistula and inner opening under direct vision. The brief steps were as follows: insertion of the anal fistula scope through external opening into the fistula; continuous injection of glycine-mannitol solution to expand and clean the foul fistula; electrocoagulation of all lesions; clearance of burnt tissues from the lumen with endoscopic brush and forceps; injection of medical fibrin glue through the inner opening; closing the inner opening by suture. Intraoperative and postoperative indices were compared between two groups.
RESULTSVAAFT group included 33 males and 9 females with mean age of (37.4±13.5) years, mean BMI of (24.3±3.2) kg/m, and mean disease course of (4.8±3.9) months. Of 42 cases, 5 had preoperative diabetes mellitus, 31 were high fistula and 11 were low fistula. FRS group included 32 males and 13 females with mean age of (42.1±15.6) years, mean BMI of (24.8±3.7) kg/m, and mean disease course of (5.7±3.6) months. Of 45 cases, 4 had preoperative diabetes mellitus, 37 were high fistula and 8 were low fistula. There were no significant differences in baseline data between two groups(all P>0.05). Compared with FRS group, VAAFT group had significantly shorter operative time [(44.6±10.5) minutes vs. (57.4±12.3) minutes, t=5.203, P=0.000], lower incidence of postoperative bleeding (14.3% vs. 33.3%,χ²=4.304, P=0.038), less pain (Visual Analogue Scale,VAS) (2.9±1.8 vs. 7.3±1.2, t=13.500, P=0.000), faster pain relief [(1.0±0.8) days vs. (4.5±1.2) days, t=15.890, P=0.000] and shorter hospital stay [(4.1±3.5) days vs.(7.5±2.3) days, t=5.389, P=0.000]. However, there were no significant differences between two groups in urinary retention rate, first postoperative fecal time and postoperative infection rate(all P>0.05). All patients were followed up for more than 6 months, FRS group had significantly higher incidence of anal incontinence than VAAFT group (20.0% vs. 2.4%, Fisher P=0.015). However, no significant difference in recurrence rate was found between VAAFT and FRS group(7.1% vs. 15.6%, Fisher P=0.317).
CONCLUSIONSCompared to traditional FRS treatment, VAAFT possesses some advantages in less injury, less pain, faster recovery, and lower postoperative anal incontinence rate. Thus, VAAFT is a superior operative choice in treatment of patients with complex anal fistula.
Adult ; Cohort Studies ; Fecal Incontinence ; Female ; Humans ; Male ; Middle Aged ; Rectal Fistula ; surgery ; Treatment Outcome ; Video-Assisted Surgery ; Young Adult
8.The efficacy and safety of morinidazole combined with appendectomy in treating purulent or gangrenous appendicitis: a randomized, controlled, double-blind, multi-center clinical trial
Yun TANG ; Mingqing TONG ; Hao YU ; Yanping LUO ; Mingzhang LI ; Yongkuan CAO ; Mingfang QIN ; Lie WANG ; Xiaoqiang WANG ; Bo PENG ; Yong YANG ; Shuguang HAN ; Chungen XING ; Bing CAI ; Jianming HUANG ; Jiazeng XIA ; Bainan LYU ; Liang XU ; Jilin YI ; Dechun LI ; Guoqing LIAO ; Xiaofeng ZHEN ; Daogui YANG ; Zhongcheng HUANG ; Haibo WANG
Chinese Journal of General Surgery 2017;32(8):678-682
Objective To assess the efficacy and safety of morinidazole combined with appendectomy in treating purulent or gangrenous appendicitis.Methods Double-blind randomized controlled multicenter clinical trial was designed and conducted.Totally 437 patients were included,219 in the control group and 218 in the experimental group.Cases of purulent or gangrenous appendicitis were enrolled and assigned to each of the two groups.The control group received ornidazole injection for 5 to 7 days while the experimental group received morinidazole injection.Both groups underwent appendectomy.Clinical response,micrombiological outcomes,overall response were evaluated.Adverse events and side effects were recorded.Results No significant difference was observed between the two groups regarding the clinical healing rate at 5-10 days after medicine withdrawal,anaerobia clearance and overall healing rates.Adverse events occurred in 140 patients (32.1%).Incidence of adverse events in the control group and the experimental group was 34.7% and 29.4%,respectively (P > 0.05).The overall incidence of side effects was 15.1% (66 cases).Side effects were less seen in the experimental group compared with that in the control group (11.5% vs.18.7%,P < 0.05).The most frequent side effects were aminotransferase rising,thrombocytosis,nausea,vomiting and electrocardiographic abnormality.Conclusions The effect of morinidazole plus operation was comparable with ornidazole in treating purulent or gangrenous appendicitis.The safety of morinidazole is better than ornidazole.
9.MicroRNA-146a polymorphism and susceptibility to gastrointestinal cancer: a meta-analysis.
Xiaohui XU ; Yiqiang ZHANG ; Qingjun LEI ; Yi WANG ; Chungen XING ; Xiaodong YANG ; Shuyu ZHANG ; Jianping CAO
Chinese Journal of Gastrointestinal Surgery 2015;18(7):718-722
OBJECTIVETo investigate the association between microRNA (miR)-146a gene polymorphisms and susceptibility to gastrointestinal cancer.
METHODSPubMed, Medline and Ovid full text databases, China Journal Full-text Database (CNKI), Articles Database and Chinese Biomedical Literature Database were researched to retrieved literatures about the association between miR-146a gene polymorphism and susceptibility to gastrointestinal cancer published from July 2010 to March 2014. Modified Jadad quality score was used to evaluate the quality of the literatures and Stata 11.0 software was used to analyze and calculate OR value of the following 5 different genotypes: allele (G vs. C), the dominant genetic model (GC+GG vs. CC), a recessive genetic model (GG vs. GC+CC) and homozygote (GG vs. CC) and heterozygote (GC vs. CC) to assess the association.
RESULTSA total of 16 studies were enrolled, including 7090 cancer patients and 9928 healthy controls. Meta-analysis showed that people with G allele was more susceptible to gastrointestinal cancer than those with C(gastric cancer: OR=1.1,95% CI:1.04-1.17, P=0.001, colorectal cancer: OR=1.09,95% CI:1.01-1.18, P=0.020); dominant model (GC+GG) was more susceptible to gastric cancer than CC (OR=1.12, 95% CI:1.02-1.22, P=0.016); recessive genetic model GG was more susceptible to gastrointestinal cancer than CC+GC (gastric cancer: OR=1.16, 95% CI:1.05-1.27, P=0.004, colorectal cancer: OR=1.13, 95%CI:1.00-1.28, P=0.047); GG homozygote was more susceptible to gastrointestinal cancer than CC (gastric cancer: OR=1.20, 95% CI:1.06-1.35, P=0.003, colorectal cancer: OR=1.19, 95% CI:1.01-1.41, P=0.042). Dominant genetic model GC+GG and CC in colorectal cancer as well as heterozygous GC and CC in gastrointestinal cancer were not significantly different(P>0.05).
CONCLUSIONmiR-146a cancer susceptibility gene polymorphism is closely associated with gastrointestinal cancers.
Alleles ; Asian Continental Ancestry Group ; China ; Gastrointestinal Neoplasms ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; MicroRNAs ; Polymorphism, Genetic
10.MicroRNA-146a polymorphism and susceptibility to gastrointestinal cancer:a meta-analysis
Xiaohui XU ; Yiqiang ZHANG ; Qingjun LEI ; Yi WANG ; Chungen XING ; Xiaodong YANG ; Shuyu ZHANG ; Jianping CAO
Chinese Journal of Gastrointestinal Surgery 2015;(7):718-722
Objective To investigate the association between microRNA (miR)-146a gene polymorphisms and susceptibility to gastrointestinal cancer. Methods PubMed, Medline and Ovid full text databases, China Journal Full-text Database (CNKI), Articles Database and Chinese Biomedical Literature Database were researched to retrieved literatures about the association between miR-146a gene polymorphism and susceptibility to gastrointestinal cancer published from July 2010 to March 2014. Modified Jadad quality score was used to evaluate the quality of the literatures and Stata 11.0 software was used to analyze and calculate OR value of the following 5 different genotypes: allele(G vs. C), the dominant genetic model(GC+GG vs. CC), a recessive genetic model (GG vs. GC+CC) and homozygote (GG vs. CC) and heterozygote (GC vs. CC) to assess the association. Results A total of 16 studies were enrolled, including 7090 cancer patients and 9928 healthy controls. Meta-analysis showed that people with G allele was more susceptible to gastrointestinal cancer than those with C (gastric cancer:OR=1.1,95% CI:1.04-1.17, P=0.001, colorectal cancer: OR=1.09,95% CI:1.01-1.18, P=0.020)﹔dominant model (GC+GG) was more susceptible to gastric cancer than CC (OR=1.12, 95% CI:1.02-1.22, P=0.016)﹔ recessive genetic model GG was more susceptible to gastrointestinal cancer than CC+GC (gastric cancer: OR=1.16, 95% CI:1.05-1.27, P=0.004, colorectal cancer: OR=1.13, 95%CI:1.00-1.28, P=0.047)﹔ GG homozygote was more susceptible to gastrointestinal cancer than CC(gastric cancer: OR=1.20, 95% CI:1.06-1.35, P=0.003, colorectal cancer: OR=1.19, 95% CI:1.01-1.41, P=0.042). Dominant genetic model GC+GG and CC in colorectal cancer as well as heterozygous GC and CC in gastrointestinal cancer were not significantly different (P>0.05). Conclusion miR-146a cancer susceptibility gene polymorphism is closely associated with gastrointestinal cancers.

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