With the development of instruments and the innovation of techniques, gastrointestinal endoscopy is expanding the scope and scale in its application. As an important component of endoscopic therapeutic techniques, the development of endoscopic resection techniques is undoubtedly remarkable. The representative techniques including endoscopic submucosal dissection, submucosal tunneling endoscopic resection and natural orifice transluminal endoscopic surgery have made endoscopic resectable scope gradually extend from the initial intramucosal to the submucosal, and even extraserosal lesions. This article reviews the state of the art and advances of main endoscopic resection techniques.

According to the latest research progress at home and abroad, and the domestic situation, China Diabetic Cellular and Interventional Therapy Technology Alliance forDiabetic Foot developed and issued the fifth edition of clinical guidelines for comprehensive interventional diagnosis and treatment of diabetic foot, which covers domestic evidence,references foreign evidence, and reflects the progress in China. The interpretation focuses on the updated key points.

ObjectiveThe role of human tumor-related calcium signal transductor 2 (TACSTD2) in promoting tumorigenesis has been noticed recently. We predicted the molecular structure and biological function of TACSTD2 by bioinformatic methods, in order to provide reference for further study of TACSTD2.MethodsThe homo sapiens TACSTD2 mRNA and protein amino acid sequences were obtained from the National Center for Biotechnology Information (NCBI) database. The bioinformatic methods were used to analyze the open reading frame(ORF) of TACSTD2, physicochemical properties, signal peptide and protein localization, subcellular localization, and prediction of transmembrane structure and secondary structure, tertiary structure, potential protein modification sites, domains, protein modification sites proteins, protein interacting with TACSTD2, biological functions of TACSTD2, and expression of TACSTD2 in human normal tissues and certain tumor types.ResultsAccording to the mRNA sequence of TACSTD2, there are 12 ORFs, and the longest is ORF1, with a total of 972bp, encoding 323 amino acids. The hydrophilic amino acid of TACSTD2 is more than that of hydrophobic amino acid, indicating that TACSTD2 belongs to hydrophilic protein. TACSTD2 is a highly conserved alkaline secreted protein with a transmembrane region both inside and outside the cytoplasm. The presence of nuclear localization signal(NLS) in the amino acid sequence of TACSTD2 suggests that TACSTD2 can locate in cell nucleus. TACSTD2 mainly distribute in cytoplasmic membrane, extracellular, nucleus and cytoplasm. The secondary structure prediction results showed that the main structure of TACSTD2 was random coil, followed by a α helix. TACSTD2 has 15 serine modification sites, 17 threonine modification sites, and 8 tyrosine modification sites. The TACSTD2 has protein interactions with Claudin(CLDN) protein family; and participating in signaling pathway such as cell surface receptor, cell proliferation, negative regulation of epithelial cell migration, and so on. Comparing with normal human tissues, its mRNA expression is up-regulated in most tumor types such as cervical cancer, lung cancer, thyroid cancer, uterine cancer, liver cancer, colorectal cancer.ConclusionAccording to the analysis of the structure and function of TACSTD2, TACSTD2 is highly-expression in multiple malignancies. It can participate in the process of proliferation, migration and adhesion of malignant tumor cells through cell surface receptor signaling pathways. This study provide reference for the further research about the function of TACSTD2.

ObjectiveTo investigate the effect of Baicalin on the apoptosis of cardiomyocytes and the expression of Akt/Amp activated protein kinase (AMPK)/mammalian rapamycin target protein (mTOR) signaling pathway in rats with chronic myocardial failure.MethodsSixty male SD rats of SPF grade were randomly divided into normal group, model group, positive control group and experimental group, with 15 rats in each group. Rats in the positive control group were given 40mg/kg losartan once a day. Rats in the experimental group were given 50mg/kg Baicalin once a day. Rats in the normal group and the model group were given the same dose of saline once a day. Each group was given gavage for 4 weeks. HE staining was used to observe the pathomorphology of cardiomyocytes. The myocardial tissue index (CAI) was detected by in situ end labeling. The expressions of Bax and bcl-2 protein in myocardium were detected by immunohistochemistry. The cardiac function was detected by echocardiography. The expression of Akt, AMPK and mTOR mRNA was detected by RT-PCR.ResultsCompared with the normal group, the apoptosis indexes of the model group, the positive control group and the experimental group were increased (P<0.05). Compared with the model group, the apoptosis indexes of the positive control group and the experimental group were decreased (P<0.05), while there was no significant difference between the positive control group and the experimental group (P>0.05). Compared with the model group, the expression of Bcl-2 protein was increased and Bax protein was decreased in the positive control group and the experimental group (P<0.05), while there was no significant difference between the positive control group and the experimental group (P>0.05). Compared with the normal group, the LVEFs of the model group, the positive control group and the experimental group were decreased, while the LVD and LVS were increased (P<0.05). Compared with the model group, the LVEFs of the positive control group and the experimental group were increased, while the LVD and LVS were decreased (P<0.05). The LVEF of the experimental group was higher than that of the control group, while the LVD and LVS of the experimental group were lower positive control group (P<0.05). Compared with the normal group, Akt, AMPK, mTOR mRNA expressions were decreased in the model group, positive control group and experimental group (P<0.05). Compared with the model group, Akt, AMPK, mTOR mRNA expressions were increased in the positive control group and experimental group (P<0.05), while there was no significant difference in Akt, AMPK, mTOR mRNA expression between the positive control group and experimental group (P>0.05).ConclusionBaicalin can alleviate myocardial injury in rats with chronic myocardial failure, and its mechanism may be related to the upregulation of Akt/AMPK/mTOR signaling pathway.

ObjectiveLymphatic epithelial cells (LECs) are important links involved in lymphatic metastasis in the microenvironment of cholangiocarcinoma. This study aims to detect the modulation of inflammatory factors and chemokines secreted by LECs after stimulation of cholangiocarcinoma cells, and observe the effects of highly expressed factors on lymphangiogenesis.MethodsThe culture medium of cholangiocarcinoma (RBE, HCCC9810), LECs stimulated by cholangiocarcinoma cell culture medium (CCM), and normal LECs were prepared. Inflammatory factors and chemokines in the culture medium were detected using protein chip. The experiments are divided into the following groups, including a blank control group, CCM group, CCM coupled with Anti-ENA-78 group, Anti-ENA-78 group, ENA-78 group, ENA-78 coupled with SB2252002, and SB225002 group. The relationship between the content of factor and time was investigated using ELISA, while the relation between target factors and lymphangiogenesis obtained by cell proliferation and tubule formation assay.ResultsWe found ENA-78, IP-10, GCP-2, MCP-2, MCP-3, MIP-3a, HCC-1, and Lymphotactin expression increased in LECs supernatant after CCM stimulation. However, I-TAC, MIP-1d, IL-10, MIG, PDGF-BB, and CXCL16 factors showed down-regulation. The secretion of ENA-78 in CCM was relatively low. By ELISA, we found that the ENA-78 protein in RBE-LECs and HCCC9810-LECs gradually increased over time, and reached the plateau phase at the point of 48h. The lymphatic tube forming ability of LECs cultured in CCM was significantly increased compared with that of the control group, and this ability could be partially weakened by ENA-78 neutralizing antibodies. In the exogenous ENA-78 protein group, the lymphatic tube formation ability was as well significantly increased compared with that in the control group, and this ability could be effectively blocked by the IL-8B inhibitor.ConclusionThe increased secretion ENA-78 of lymphatic epithelial cells induced by cholangiocarcinoma may play a role in promoting lymphangiogenesis through the IL-8B receptor.

ObjectiveNano-graphene oxide quantum dots (GOQDs) can be used to target fluorescent markers. The stem cell labeling is an important method in studying stem cell treatments. Our study aims to explore the possibility of using GOQDs as living cell fluorescent marker materials for human periodontal ligament stem cells (hPDLSCs), and to evaluate the biosecurity and effect as live cell fluorescence markers of GOQDs.Methods GOQDs were testified by TEM, DLS, UV-vis, and PL spectra. hPDLSCs were obtained by tissue cultivation and separated by single cell-derived colony selection. Then the source of the cells was carried out by immunocytochemical staining of anti-vimentin, anti-cytokeratin, and multipotent differentiation was used in the identification of stem cells. hPDLSCs were incubated with different concentrations of GOODs (0, 10, 25, and 50 μg/mL) for 24h and 72 h. Cytotoxicity and proliferation effects were determined using CCK-8, and cell cycles were detected using flow cytometry after the co-culture of GOQDs and hPDLSCs. The fluorescent labeling effect of GOQDs was tested using laser scanning confocal microscopy.ResultsThe characterization of GOQDs showed that the nanoparticles were evenly dispersed in water and showing blue light at 365 nm. TEM and DLS showed GOQDs had good dispersion, and the particle size was (6.36±1.41) nm. Immunocytochemical staining of anti-vimentin was positive while anti-cytokeratin was negative. The results of cytotoxicity showed there were no significant differences in cell activity after incubated with different concentrations of GOODs (0, 5, 10, 25, 50, 100, 200, and 400 μg/mL) (P>0.05), and there was no significant decrease in cell activity between 24h and 72h (P>0.05). There was no significant difference in the proportional distribution of G1, G2, and S phases between the two concentrations of GOQDs (0 μg/mL and 50 μg/mL) (P>0.05). Fluorescent images showed that GOQDs could enter the cell membrane and increase the fluorescence intensity at the concertation of 50 μg/mL.ConclusionGOQDs were confirmed to have good biocompatibility and could be used for live cell labeling of hPDLSCs.

ObjectiveRenal fibrosis is the basic pathological process of chronic kidney disease. To explore the protective effect of sildenafil (Sil) on renal fibrosis in mice, and provide experimental evidence for the clinical application of sildenafil in the treatment of renal fibrosis.Methods90 Kunming mice were randomly divided into three groups. Sham operation group (n=30), the mice only had ureteral separation, no ligation and ureteral clipping, which was subcutaneously injected with 0.9% NaCl solution in dose of 1 mL/(10 g·d); UUO model group (n=30), the UUO model was prepared by separating and ligating ureters in mice, and those were given subcutaneous injection with 0.9% NaCl solution in 1 mL/(10 g·d); UUO+Sil medicated group (n=30), mice were subcutaneously injected with sildena in 12 mg/(kg·d) at the same time every day for 14 days from the 1st day of UUO model. On the 3rd, 7th and 14th day, 10 mice whoes blood from eyeball was collected to determine serum creatinine and urea nitrogen were randomly selected from each group. HE and Masson staining were performed on the left kidney tissue to observe the pathological changes of the kidney tissue. The levels of Akt and GSK-3β protein and its phosphorylation in renal tissue were determined by western blot.ResultsAfter 3 days in UUO model, the contents of serum creatinine (63.10±2.90mol/L ) and urea nitrogen (12.87±0.40mmol/L) in the UUO group were significantly higher than those in the sham group [(26.00±3.70) mol/L, (8.07±0.60) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (13.59±0.30) mmol/L] on the 7th day were higher than those in the sham group [(29.18±3.50) mol/L, (9.14±0.50) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (15.03±0.50) mmol/L] on the 14th day were also significantly higher than those in the sham group [(29.74±2.50) mol/L, (9.90±0.20) mmol/L] (P<0.05). Compared with UUO group, the creatinine of mice on the 3rd, 7th and 14th day in the medicated group was lower (P<0.05). Compared with UUO group , urea nitrogen on the 3rd, 7th and 14th day in the medicated group was decreased (P<0.05). Compared with the sham operation group, the expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the UUO group were significantly decreased (P<0.05), while the protein expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the medicated group were significantly increased compared with the UUO group (P<0.05). On the 7th day in UUO model, there were many changes included atrophic renal tubular epithelial cells, dilated lumen, widened interstitium and more infiltrated inflammatory cells. On the 14th day in UUO, the above changes were more obvious, interstitial fibroblast hyperplasia and interstitial fibrosis, and the above pathological changes were reduced in the medicated group compared with the UUO model group. The collagen fibers in the UUO model group increased gradually with time. On the 14th day in UUO, the collagen fibers in the interstitium increased significantly, the tubular epithelium was damaged, and the red staining cells became lighter. These findings were less severe in the medicated group than in the UUO model group.ConclusionSildenafil can alleviate renal damage caused by renal fibrosis. Sildenafil inhibited renal fibrosis in UUO model, and its mechanism may be related to up-regulation of Akt/GSK3β pathway.

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

ObjectiveLupus mesenteric vasculitis (LMV) can lead to extensive necrosis of the small intestine, and it is easy to be misdiagnosed and missed in the early stage of the disease. This study aims to evaluate the clinical significance of serum D-dimer level in the early diagnosis of LMV.MethodsRetrospective analysis was performed on 38 patients with systemic lupus erythematosus (SLE) admitted to Nanjing Drum Tower Hospital from January 2006 to January 2019. There were 15 LMV patients (LMV Group) and 23 non-LMV patients (Non-LMV Group). The main observation indicators of statistical analysis were serum D-dimer level on the first day of treatment in the two groups, while the secondary indicators included patient general condition, SLE disease activity index (SLEDAI), enhanced CT examination results, laboratory examination results and serum D-dimer level after treatment.ResultsThere was no significant difference in age, SLE duration and SLEDAI between the two groups (P>0.05). On admission, CT showed LMV patients with intestinal dilatation, mesenteric edema and typical target symptoms. After high-dose hormone therapy, the dilatation of intestinal canal and intestinal wall were significantly relieved, and the target signs on CT disappeared before discharge. The serum D-dimer level of patients in the LMV Group [917 (756,1848) μg/L] was significantly higher than that in the Non-LMV Group [570 (356,896) μg/L], and the difference was statistically significant (P=0.006). ROC curve analysis showed that the critical value of serum D-dimer in early diagnosis of LMV was 624 μg/L, and the sensitivity and specificity were 93% and 61%, respectively (AUC=0.77).ConclusionSerum D- dimer level can be used as an effective index for early diagnosis of LMV patients.

ObjectiveAt present, there are few reports on the therapeutic effect of probiotic supplements in patients with dietary-controlled gestational diabetes mellitus (GDM). This study aims to evaluate the effect of probiotic supplements on insulin resistance in patients with dietary-controlled GDM.Methods122 pregnant women with dietary-controlled GDM who could control blood glucose less than 92 mg/dL through diet and exercise were selected from the Obstetrics Department in Bayannur Hospital from February to December 2018. The patients were randomly divided into two groups: Probiotics Group (probiotic supplements containing bifidobacterium and lactobacillus) and Placebo Group (placebo capsules). 61 patients in each group were treated continuously for 4 weeks. The main evaluation index was the mean difference of fasting blood glucose, fasting plasma insulin and insulin resistance index (HOMA-IR) between the two groups, and the secondary evaluation index was the change of maternal weight after intervention.ResultsThe increase of fasting blood glucose [(0.59±6.42)mg/dL], fasting plasma insulin [(1.14±1.95)mIU/mL] and HOMA-IR (0.27±0.45) in the Probiotics Group after intervention were significantly lower than those in the Placebo Group [(4.78±7.47 mg/dL), (3.86±1.82) mIU/mL, (0.86±0.59)], and the difference was statistically significant (P < 0.05). There was no significant difference in total weight gain, neonatal birth weight and neonatal hypoglycemia between the two groups (P>0.05).ConclusionDuring pregnancy, probiotic supplements for four weeks in patients with dietary-controlled GDM can reduce fasting blood glucose and increase insulin sensitivity. Therefore, probiotic supplements can be used as adjunctive therapy for blood glucose control in patients with dietary-controlled GDM.