Objective : To explore the potential targets, pathways and related mechanisms of artesunate(ART) in the treatment of hepatocellular carcinoma(HCC) based on network pharmacology and Bioinformatics. Methods: The potential targets of ART were screened through pharmmapper database, PPI network was constructed and visual analysis was performed.The data of 424 HCC samples were downloaded from TCGA database, the data information of potential target genes were screened, and the differentially expressed target genes were analyzed.The key target genes were screened by univariate-multivariate COX regression analysis.Molecular docking software was used to conduct molecular docking between ART and key target genes.Differential expression and survival analysis of key target genes were performed using network database GEPIA2. KEGG pathway enrichment analysis was performed by R language. The effects of ART on the proliferation and migration of HCC cells were verified by MTS assay and scratch test. The expression of FABP5 in HCC cells was verified by qPCR and Western blot. Western blot was used to verify the protein changes of PI3K/AKT pathway. Results : A total of 282 potential target genes were screened by network pharmacology. Finally,three key target genes were screened out. The survival analysis of FABP5 in HCC was statistically significant(P<0. 01). Molecular docking showed that ART and FABP5 had the highest binding energy. Pathway enrichment analysis showed that FABP5 was mainly enriched in PI3K/AKT signaling pathway. Cell experiments verified that ART could inhibit the expression level of FABP5,that ART could regulate the PI3K/AKT pathway,and that ART could inhibit the proliferation and migration of HCC cells. Conclusion FABP5 may regulate the PI3K/AKT pathway by inhibiting FABP5 and thus affect HCC cell proliferation and migration,and FABP5may serve as a new target gene for ART therapy of HCC.

Objective:To investigate the impact of Notch signaling pathway on the migration of human hepatic carcinoma cells and the expression of E-cadherin and COX-2 in these cells.Methods:Cultured hepatic carcinoma cell lines (SMMC-7721,MHCC97H),and normal non tumor liver cell line (HL-7702) in vitro.Transwell cell was used to measure the cell's capacity of invasion and migration.Western blot was used to measure the expression level ofNotch1,E-cadherin,COX-2 protein.DAPT was used to block the Notch signaling pathway,and compared the ability of invasion and migration between hepatic carcinoma cell lines and normal non tumor liver cell line,and the change of expression level of E-cadherin and COX-2 protein in hepatic carcinoma cells.Results:The migration ability of SMMC-7721 cells and MHCC97H cells were higher than HL-7702 cells,the difference was statistically significant (P＜0.05);Compared to HL-7702 cells,the expression level of Notch1 and COX-2 in MHCC97H cells and SMMC-7721 cells significantly increased,the expression level of E-cadherin decreased significantly (P＜0.05);After DAPT treatment,the migration ability of SMMC-7721 cells,MHCC97H cells were weaker than the control group,the difference was statistically significant (P＜0.05);After DAPT treatment,the expression of COX-2 and Notch1 in SMMC-7721 and MHCC97H cells decreased significantly,while the expression of E-cadherin significantly increased (P＜0.05).Conclusion:Notch signaling pathway plays an important role in the process of liver cancer cell migration and invasion,and its mechanism is related to the expression of E-cadherin and COX-2.

BACKGROUNDEndoscopic submucosal dissection of the esophagogastric junction is the most difficult gastric and esophageal dissection procedure. No reports of endoscopic submucosal dissection for Siewert type II carcinoma of the esophagogastric junction have compared the outcomes of endoscopic submucosal dissection for all three Siewert types of adenocarcinoma. This study aimed to evaluate the efficacy and safety of endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction.

METHODSFrom October 2008 to June 2013, 73 patients underwent endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction. The patients were prospectively evaluated regarding the executability of the technique, short-term results of the procedure, en bloc resection rate, curative resection rate, complications and additional treatment after endoscopic submucosal dissection, and follow-up outcomes.

RESULTSSixty-eight of the 73 patients (93.2%) underwent en bloc resection; the mean maximum specimen diameter was 33.7 mm. Fifty-seven of 61 patients (93.4%) who underwent curative resection were successfully followed-up for 1.0 to 56.0 months (average, 24.1 months). Local recurrence developed in one patient with high-grade intraepithelial neoplasm. Twelve patients underwent noncurative resection, including lateral resection margin residues in three, vertical resection margin residues in one, signet ring cell carcinoma or undifferentiated adenocarcinoma in four, lymphatic or vessel invasion in one, vertical residual margin residues combined with signet ring cell carcinoma in one, and undifferentiated adenocarcinoma with lymphatic or vessel invasion in two. In the noncurative resection group, one patient was lost to follow-up, seven underwent additional surgery, and the remaining four were periodically followed up; none had local recurrence or distant metastases. The only complication was delayed bleeding in three patients, which was successfully controlled by conservative treatment or endoscopic therapy.

CONCLUSIONSEndoscopic submucosal dissection is safe and effective for intraepithelial neoplasia of the esophagogastric junction. R0 en bloc resection is possible and can avoid the risk of local recurrence.

Adult ; Aged ; Aged, 80 and over ; Carcinoma in Situ ; surgery ; Dissection ; adverse effects ; methods ; Esophageal Neoplasms ; surgery ; Esophagogastric Junction ; surgery ; Female ; Gastric Mucosa ; surgery ; Humans ; Male ; Middle Aged ; Prospective Studies

This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness. Twenty-four Wistar rats were randomly divided into three groups: CON group (n=8), control; SUS-14 d group (n=8), tail-suspension for 14 days; SUS-21 d group (n=8), tail-suspension for 21 days. Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR. Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry. Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups. The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group, and significantly lower than those in CON group (Occldin: 0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1: 0.82±0.01 vs 1.00±0.02 vs 1.55±0.01, P<0.01). Moreover, the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group, and significantly higher than those in CON group (DAO: 27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate: 37.86±0.74 vs 28.26±1.01 vs 17.76±0.91, P<0.01). There were significant negative correlations between occludin or ZO-1 expression levels and DAO (r (2)=0.9014, r (2)=0.9355, P<0.01) or d-lactate levels (r (2)=0.8989, r (2)=0.9331, P<0.01). Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model. The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.

This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness.Twenty-four Wistar rats were randomly divided into three groups:CON group (n=8),control; SUS-14 d group (n=8),tail-suspension for 14 days;SUS-21 d group (n=8),tail-suspension for 21 days.Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR.Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry.Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups.The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group,and significantly lower than those in CON group (Occldin:0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1:0.82±0.01 vs 1.00±0.02 vs 1.55±0.01,P＜0.01).Moreover,the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group,and significantly higher than those in CON group (DAO:27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate:37.86±0.74 vs 28.26±1.01 vs 17.76±0.91,P＜0.01).There were significant negative co rrelations between occludin or ZO-1 expression levels and DAO (r2=0.9014,r2=0.9355,P＜0.01) or d-lactate levels (r2=0.8989,r2=0.9331,P＜0.01).Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model.The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.

BACKGROUND: Crohn's disease is complex and lack of specificity; meanwhile, it is related to diseased regions, areas,severity and complications in intestine. Otherwise, it is difficult to diagnose. The etiological factors are still unclear and radical therapy is lack recently. Therefore, clinical manifestations and therapeutic measures of Crohn' disease at home are different from those abroad.OBJECTIVE: To compare the clinical characteristics and therapeutic differences between the Chinese and American patients with Crohn's disease.DESIGN: Retrospective case analysis.SETTING: Department of Digestion, General Hospital of Chinese PLA.PARTICIPANTS: A total of 85 Chinese patients with Crohn's disease were selected from General Hospital (the 301 Hospital) of Chinese PLA from 1985 to 2004; meanwhile, a total of 68 American patients with Corhn's disease were selected from Cleveland Clinic Florida (CCF) from 1985 to 2004. Diagnostic criteria were based on WHO standards and all patients were diagnosed according to endoscope, X-ray manifestations and pathological characteristics.METHODS: Clinical data, including age, sex, family history, external manifestations of intestine, diseased regions and characteristics, drug treatment and surgical therapy, were compared between Chinese and American patients.Otherwise, enumeration data were compared with Chi-square test.MAIN OUTCOME MEASURES: Age, sex, family history, extra intestinal manifestations, diseased regions and characteristics, drug treatment and surgical therapy of Crohn's disease.RESULTS: ① General status and extra intestinal manifestations of intestine: The ratio of male and female patients in the 301 hospital was 1.74:1 and in CCF was 1:1.43. The incidences of positive family history and extra intestinal manifestations were 7% and 34%, which were higher in CCF than those in the 301 hospital (1%, 14%, x2=4.631 2, 8.315 0,P ＜ 0.05). ② Diseased regions and pathological characteristics: The terminal ileum was involved at most (69%) and no patients had perianal diseases in the 301 hospital and the main pathological characteristics were ulcer (66%) and obstruction (14%). Those were higher than those of patients in CCF (25%, 4%, x2=25.309 2, 4.024 6, P＜ 0.05).Compared with the 301 hospital, the patients in CCF had more pathological changes in colon and rectum and more perianal diseases and intra-abdominal fistulas were involved (51%). The incidences of perianal diseases and intra-abdominal fistulas were 51% and 9%, which were higher than those of patients in the 301 hospital (0, 6%, x2=38.429 0, 0.148 2, P ＜ 0.05). ③ Therapy: The main selections of medicine were sulfasalazine salicylazosulfapyridine (SASP, 54%), 5-aminosalicvlic acid (5-ASA, 19%) and metronidazole (21%) in 301 hospital, but in CCF, steroids (60%),azathioprine (34%) and infliximab (46%) were the main selections of medicine. Rates of surgical therapy were higher in CCF than those in the 301 hospital (96%, 49%, x2=36.145 9, P ＜ 0.01).CONCLUSION: There are significant differences in clinical characteristics and therapeutic measures between Chinese and American patients with Crohn's disease, which is one of the reasons for the two hospitals to take different treatments.

Objective To investigante the effect on the count of intestinal mast cell in rats of botulinum toxin-A.Methods 40 Wistar rats of 8 weeks age were divided into four groups randomly and evenly.4 units,2 units,1 unit BTA was injected in every rat peritoneally in group A,B,C.D was control group.The samples of small intestine,ileocecal junction and distal colon was stained with toluidine blue improved staining method for mast cell at 4 weeks after injection.Results The counts of mast cell in all the samples in group A and B[small intestine (5.16?2.74) and (4.50?3.19);ileocecal junction (3.83?1.78) and (3.33?2.50);distal colon (7.00?2.53) and (7.50?3.29),respectively] were smaller than those of group D[(11.16?4.48),(8.50?3.04),(13.66?4.83),P

Data warehouse of Fuzhou General Hospital as the example, the basic conception and requirements of data warehouse are introduced in this paper. The design and construction of data warehouse are described from the aspects of subject determination, data preparation, model building, model evaluation and interpretation, and model application and consolidation. The main function of the data warehouse of Fuzhou General Hospital is also mentioned.

Objective: In recent years,botulinum toxin type A(BTX-A) has been investigated for the treatment of pain.This experiment was to investigate the antinociceptive effect of BTX-A intraperitoneal injection on visceral pain of rats and its effect on intestinal AChE and SP expression.Methods: 72 male adult Wistar rats were divided into four groups: BTX-A(2U,4U,and 6U) or vehicle(2ml) was injected intraperitoneally in B,C,D and A group.6 Rats of every group were challenged with acetic acid intraperitoneal injection after 1,4 and 8 weeks respectively.After abdominal writhing behaviors were monitored,the intestinal samples were immunohistochemical stained for AChE and SP examination.Results: At the end of one week,writhing test scores of rats in group C and D were decreased significantly compared with group A(P

Objective To compare the clinical characteristics and therapeutic differences between the Chinese and American patients with Crohn′s disease. Methods 85 patients in the Chinese PLA General Hospital (301 Hospital) and 68 patients in the Cleveland Clinic Florida (CCF), USA with Crohn′s disease from 1985 to 2004 were studied retrospectively. The statistic data were analyzed with Chi-square tests. Results The ratio of male and female patients in 301 Hospital was 1.74∶1 and in CCF was 1∶1.43. The incidence of positive family history and extra intestinal manifestations in CCF were higher than in 301 Hospital (P