ObjectiveTo investigate the protective mechanism of emodin(大黄素) on intestinal mucosal injury induced by intestinal ischemia/reperfusion(I/R) in rats.Methods Thirty male Wistar rats were randomly divided into three groups,namely sham operation group(Group A),group of ischemia 45 minutes followed by reperfusion 6 hours(Group B),emodinpretreated group(Group C).The superior mesenteric artery was occluded and then released to produce the intestinal I/R model in rats.Group C was administrated emodin intravenously(2.5 mg/kg) before 30 minutes of the operation.In the sham operation group and model group,similar volume of normal saline was administered respectively.After 45 minutes of ischemia and 6 hours of reperfusion, the blood was collected from the inferior vena cava respectively in each group.Afterwards,the rats were sacrificed,and the mesenteric lymph node(MLN) and small intestinal tissues were taken for pathological analysis by light microscopy.The serum levels of intestinal fatty acid binding protein(IFABP),nitrogen monoxidum(NO),tumor necrosis factor-?(TNF-?),and the activities of malondialdehyde(MDA),superoxide dismutase(SOD),myeloperoxidase(MPO)in the small intestinal tissues were measured,and the rates of bacterial translocation(BT) in blood and MLN were examined at 6 hours after reperfusion in each group. Results The contents of IFABP,NO,TNF-?,MDA and MPO were significantly lower(all P

Objective To screen the high specific and sensitive monitoring indications in the diagnosis of intestinal barrier dysfunction.Methods A total of 70 critical patients with intestinal barrier dysfunction and acute physiology and chronic health evaluation (APACHE) Ⅱ score≥8 and over the same period 41 patients without intestinal barrier dysfunction and APACHE Ⅱ score≤6 were recruited.The general information,histories,symptoms,physical signs,24 hours urine output and the condition of mechanical ventilation treatment were recorded.The venous blood was taken for bacteria culture,white blood cell counting,creatinine level,diamine oxidase (DAO) activity,D-lactic acid,intestinal fatty acid binding protein (IFABP) and endotoxin level testing.The urine was taken for urinary IFABP level testing.Twenty-four hours urine was reserved for 24 hours total urinary IFABP testing.The factors which might influence intestinal barrier dysfunction were analyzed by univariate analysis and multivariate analysis.The measurement data were analyzed by t test and the count data were analyzed by x2 test.The factors were screened according to receiver operating characteristic (ROC) curve.Results The factors related with intestinal barrier dysfunction were white blood cell counting (OR=3.971,P=0.046),plasma endotoxin level (OR=7.857,P=0.005)and 24 hours total urinary IFABP (OR=11.154,P=0.001).The areas under the ROC curve (AUC)of plasma endotoxin level and 24 hours total urinary IFABP were 0.852 and 0.820 respectively (both P＜0.01).The critical value was 8.0 pg/ml and 17.12 ng respectively.The sensitivity was 97.8％ and 84.4％.The specificity was 66.7％ and 72.7％.Conclusion Once critical patients presented certain gastrointestinal symptoms and physical signs with plasma endotoxin level ＞8.0 pg/ml and or 24 hours total urinary IFABP ＞17.12 ng,which might indicate intestinal barrier dysfunction.

Objective To observe the effect of excretory/secretory products from Trichinella spiralis adult worms(AES)on cecal ligation and puncture(CLP)?induced sepsis in mice. Methods Forty?eight BALB/c mice were randomly divided into 3 groups:a sham operation group(PBS+sham group,Group A),a CLP?induced sepsis group(PBS+CLP group,Group B)and an AES treatment group(AES+ CLP group,Group C). The mice of each group were intraperitoneally injected with 25 μg of AES or PBS only as a control in a total volume of 200μl. Eight mice from each group were selected randomly for survival analy?sis of 96 hours. The other 8 mice in each group were observed for pathological changes in the lung,liver and kidney tissues by HE staining 12 h after CLP,and then determined for the detection of cytokines including TNF?α,IL?1β,IL?6,IL?10 and TGF? βin the sera by ELISA. Results The difference among the survival rates of mice in the 3 groups was statistically significant (χ2=21.16,P<0.05). Compared to Group A(100%),the survival rate of mice in Group B(0)decreased significantly(P<0.05),and also the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group B increased signifi?cantly after CLP. Compared with the mice in group B,the survival rate of those in Group C(70%)increased significantly(P<0.05),and the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group C decreased significantly after the treatment with AES. The differences among the levels of pro?inflammatory cytokines TNF?α(F=27.11,P<0.05),IL?1β(F=18.75,P<0.05)and IL?6(F=100.93,P<0.05)in the sera of the mice in the three groups were statistically signifi?cant. Compared with the mice in Group A,the levels of the 3 cytokines of those in Group B increased significantly(all P <0.05). However,after the treatment with AES,the levels of the pro?inflammatory cytokines of those in Group C decreased signifi?cantly(all P<0.05). The differences among the levels of immunoregulatory cytokines IL?10(F=10.88,P<0.05)and TGF?β(F=11.37,P<0.05)in the sera of the mice in the three groups were also statistically significant. Compared with the mice in Group B,the levels of IL?10 and TGF?β of those in Group C were higher after treatment with AES(both P<0.05). Conclu?sion T. spiralis AES has a therapeutic potential for alleviating sepsis induced by CLP in mice.

OBJECTIVE: To investigate the differentially expressed genes between gastric cancer and normal gastric mucosa by bioinformatics analysis, identify the important gene participating in the occurrence and progression of gastric cancer, and predict the functions of these genes. METHODS: The gene expression microarray data GSE100935 (including 18 gastric cancer samples and normal gastric mucosal tissues) downloaded from the GEO expression profile database were analyzed using Morpheus to obtain the differentially expressed genes in gastric cancer, and a cluster analysis heat map was constructed. The online database UALCAN was used to obtain the expression levels of these differentially expressed genes in gastric cancer and normal gastric mucosa. The prognostic value of the differentially expressed genes in gastric cancer was evaluated with Kaplan-Meier survival analysis. GO functional enrichment analysis was performed using Fun-Rich software, and the STRING database was exploited to establish a PPI network for the differentially expressed genes. RESULTS: A total of 45119 differentially expressed genes were identified from GSE100935 microarray data. Analysis with UALCAN showed an obvious high expression of EXD3 gene in gastric cancer, and survival analysis suggested that a high expression level of EXD3 was associated with a poorer prognosis of the patients with gastric cancer. GO functional enrichment analysis found that the differentially expressed genes in gastric cancer were involved mainly in the regulation of nucleotide metabolism and the activity of transcription factors in the cancer cells. CONCLUSIONS EXD3 may be a potential oncogene in gastric cancer possibly in relation to DNA damage repair. The up-regulation of EXD3 plays an important role in the development and prognosis of gastric cancer, and may serve as an important indicator for prognostic evaluation of the patients.
Computational Biology ; Databases, Genetic ; Exonucleases ; genetics ; Gastric Mucosa ; chemistry ; enzymology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins ; genetics ; Prognosis ; Stomach Neoplasms ; enzymology ; genetics ; mortality

Objective: To investigate the prognosis and influencing factors of postoperative low anterior resection syndrome (LARS) for rectal cancer patients undergoing laparoscopic sphincter-preserving radical resection. Methods: A retrospective case-control study was used in this study. Clinical data of 268 rectal cancer patients undergoing laparoscopic sphincter-preserving radical resection at Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2016 to January 2018 were retrospectively collected. Inclusion criteria: (1) operation procedure was total mesorectal excision (TME) and sphincter-preserving radical resection; (2) rectal cancer was confirmed by postoperative pathology; (3) age of patient was ≥ 18 years old. Exclusion criteria: (1) patient who had history of pelvic surgery and pelvic fractures, which would affect the anorectal function; (2) patient who had history of preoperative chronic constipation and irritable bowel syndrome, which would affect defecation; (3) patient who developed postoperative complications, such as anastomotic leakage, which would affect defecation function; (4) patient who received long-term use of drugs, which would affect the function of gastrointestinal tract or anus; (5) patient suffered from mental illness, who was unable to communicate properly; (6) patient who was lack of clinical data or had incomplete clinical data. Patients were followed up at 3, 6 and 12 months postoperatively, and LARS was diagnosed and graded according to the LARS score scale. The LARS score ranged from 0 to 42 points, and 0 to 20 was difined as no LARS, 21 to 29 was mild LARS, and 30 to 42 was severe LARS. LARS score >20 points at any time point was defined as postoperative LARS. Severe LARS transferring into mild LARS and mild LARS transferring into no LARS was defined as symptom improvement. Incidence and outcomes of LARS were evaluated. The factors associated with LARS outcomes were analyzed using χ² test and logistic regression model. Results: A total of 268 patients were enrolled. The incidence of LARS was 42.9% (115/268), 32.5% (87/268) and 20.1% (54/268) at 3, 6, and 12 months postoperatively respectively, and no new case of LARS was found after 3 months postoperatively. The incidence of mild LARS was 25.7% (69/268), 17.2% (46/268) and 8.6% (23/268) at 3, 6, and 12 months postoperatively respectively, and mild LARS incidence at 6 months was significantly lower than that at 3 months (χ²=5.857, P=0.016), and was significantly higher than that at 12 months (χ²=8.799, P=0.003). The incidence of severe LARS was 17.2% (46/268), 15.3% (41/268) and 11.6% (31/268) at 3, 6, and 12 months postoperatively respectively, without significant difference among 3 time points (all P>0.05). The improvement rate within one year after surgery in patients with mild LARS diagnosed at 3 months was significantly higher than that in patients with severe LARS (88.4% vs. 32.6%, χ²=38.340, P<0.001). Univariate analysis showed that female, distance from anastomosis to anal verge < 5 cm and tumor diameter ≥ 5 cm were associated with unsatisfied LARS outcomes (all P<0.05). Logistic regression analysis showed that distance from anastomosis to anal verge <5 cm was an independent risk factor for LARS outcome (OR=3.589, 95% CI: 1.163 to 2.198, P<0.001). Conclusions The incidence of LARS after laparoscopic sphincter-preserving radical resection decreases with time. The improvement rate within postoperative 1-year of severe LARS is lower than that of mild LARS. Low anastomotic position may lead to impaired improvement of LARS.

OBJECTIVE: To explore association of the expression levels of adenylate cyclase-associated protein 2 (CAP2) in gastric cancer tissues with the histopathology and long-term prognosis of the malignancy. METHODS: This study was conducted among a total of 105 patients with gastric cancer undergoing radical gastrectomy in our hospital between January, 2010 and October, 2013. Immunohistochemistry was used to quantitatively assess the expression of CAP2 in gastric cancer tissues and the adjacent tissues. Based on the median relative expression level of CAP2 of 3.5, the patients were divided into low CAP2 expression group (=52) and high CAP2 expression group (=53). The Cox regression model was used to analyze the effect of CAP2 expression on the 5-year survival rate of the patients, and ROC curve analysis was used to assess the predictive value of CAP2 expression for the patients' long-term survival. RESULTS: Immunohistochemical analysis showed that the expression levels of CAP2 ( < 0.01) and Ki67 ( < 0.01) were significantly higher in gastric cancer tissues than in the adjacent tissues, and the expression level of CAP2 was positively correlated with Ki67 ( < 0.01), peripheral blood CEA ( < 0.01) and CA19-9 ( < 0.01). The percentages of patients with CEA≥5 μg/L, CA19-9≥37 kU/L, pathological grade of G3-G4, T stage of 3-4, and N stage of 2-3 were significantly higher in patients with high CAP2 expression than in those with low CAP2 expression ( < 0.05). Kaplan- Meier survival analysis showed that the 5-year survival rate was significantly lower in patients with a high CAP2 expression ( < 0.01). A high expression level of CAP2, CEA≥5μg/L, CA19-9≥37 and pathological grades G3-G4 were all independent risk factors for shortened 5-year survival after radical gastrectomy ( < 0.01). With the relative expression level of 3.45 as the cut-off value, the sensitivity of CAP2 was 70.15% for predicting death 5 years after the surgery, with a specificity of 71.05% and an area under the curve of 0.779 ( < 0.01). CONCLUSIONS CAP2 is highly expressed in gastric cancer tissues in close relation with the tumor progression. CAP2 is an independent risk factor for 5-year survival rate after radical gastrectomy for gastric cancer and can be of clinical value in prognostic evaluation of the patients.
Adaptor Proteins, Signal Transducing ; metabolism ; Gastrectomy ; Humans ; Immunohistochemistry ; Membrane Proteins ; metabolism ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; diagnosis ; metabolism ; pathology ; Survival Rate

Objective : To explore the mechanism of Wenyang Shengji Ointment (温阳生肌膏, WYSJO) in the treatment of diabetic wounds from the perspective of network pharmacology, and to verify it by animal experiments. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and related literature were used to screen active compounds in WYSJO and their corresponding targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), DrugBank, PharmGkb, and Therapeutic Target Database (TTD) databases were employed to identify the targets associated with diabetic wounds. Cytoscape 3.9.0 was used to map the active ingredients in WYSJO, which was the diabetic wound target network. Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) platform was utilized to construct protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) andGene Ontology (GO) enrichment analyses were performed to identify signaling pathways between WYSJO and diabetic wounds. AutoDock 1.5.6 was used for molecular docking of core components in WYSJO to their targets. Eighteen rats were randomly divided into control, model, and WYSJO groups (n = 6). The model and WYSJO groups were used to prepare the model of refractory wounds in diabetes rats. The wound healing was observed on day 0, 5, 9, and 14 after treatment, and the wound tissue morphology was observed by hematoxylin-eosin(HE) staining. The expression levels of core genes were detected by quantitative real-timepolymerase chain reaction (qPCR). Result: A total of 76 active compounds in WYSJO, 206 WYSJO drug targets, 3 797 diabetic wound targets, and 167 diabetic wound associated WYSJO targets were screened out through network pharmacology. With the use of WYSJO-diabetic wound target network, core targets of seven active compounds encompassing quercetin, daidzein, kaempferol, rhamnetin, rhamnocitrin, strictosamide, and diisobutyl phthalate (DIBP) in WYSJO were found. GO enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve lipopolysaccharide, bacteria-derived molecules, metal ions, foreign stimuli, chemical stress, nutrient level, hypoxia, and oxidative stress in the biological processes. KEGG enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve advanced glycation end products (AGE-RAGE), p53, interleukin (IL)-17, tumor necrosis factor (TNF),hypoxia inducible factor-1 (HIF-1), apoptosis, lipid, atherosclerosis, etc. The results of animal experiments showed that WYSJO could significantly accelerate the healing process of diabetic wounds (P < 0.05), alleviate inflammatory response, promote the growth of granulation tissues, and down-regulate the expression levels of eight core genes [histone crotonyltransferase p300 (EP300), protoc gene-oncogene c-Jun (JUN), myelocytomatosis (MYC), hypoxia inducible factor 1A (HIF1A), mitogen-activated protein kinase 14 (MAPK14), specificity protein 1 (SP1), tumor protein p53 (TP53), and estrogen receptor 1 (ESR1)] predicted by the network pharmacology (P < 0.05). Conclusion The mechanism of WYSJO in treating diabetes wounds may be closely related to AGE-RAGE, p53, HIF-1, and other pathways. This study can provide new ideas for the pharmacological research of WYSJO, and provide a basis for its further transformation and application.