Mammalian target of rapamycin ( mTOR) is a kind of Ser/Thr kinase existing in mammalian cells can regulate cell proliferation, migration and angiogenesis.mTOR including two different complex forms as mTORC1 and mTORC2 .Rapamycin and rapalogs were soon found to have powerful immunosuppressant prop-erties and thus be valuable for preventing the progress of the artery atheromatous by inhibiting the function of mTORC1.But long-term rapalogs administration may increase the side actions such as mTORC1 resistance, mTORC2 inhibition, dyslipidemia.The clinical application of drug combination and dosage optimization may reduce adverse events.

Objective To analyze the nutritional status of patients with continuous ambulatory peritoneal dialysis and explore reasonable and effective nursing measures.Methods Nutritional assessment was performed in 60 patients with continuous ambulatory peritoneal dialysis,using subjective integrated nutritional assessment,dietary analysis,measurement of biochemical indexes of the human body to analyze the factors that might affect the nutritional status of patients.Results 60 cases of malnutrition occurrd in 20 patients (33.3per cent),mainly due to insufficient protein and energy intake,inadequate dialysis,peritoneal inflammation,metabolic acidosis,psychosocial factors and not using erythropoietin,and so on.Conclusions Measures such as emphasis paid to malnutrition status of continuous ambulatory peritoneal dialysis patients,giving guidance of rational diet,performing full implementation of nursing measures according to the related factors,can improve the nutritional status of patients and improve patients' quality of life.

Objective To explore the mechanism of LMWH therapy for SAP.Methods 48 wistar rats were random divided into 3 groups,sham group(S group),severe acute pancreatitis group(SAP group)and LMWH therapy group(H group).Serum amylase,IL-6,acinar cell apoptosis and the activity of NF-κB were detected and compared.Results The expression of amylase and IL-6 in SAP group was significantly higher than that in H group(P＜0.01).The apoptosis index of acinar cell in SAP group wag significantly lower than that in H group(P＜0.01),while the activity of NF-κB in SAP groupwas stronger than that in H group.Conclusions LMWH therapy may ameliorate SAP by inducing acinar cell apoptosis through suppressing the activity of NF-κB.

Objective To evaluate the role of renal cell apoptosis in acute kidney injury (AKI) induced by sepsis in mice. Methods Forty-five male C57BL/6 mice were randomly assigned into 3 groups ( n = 15 each):sham operation group (group S), cecum ligation and puncture group (group CLP) and CLP + caspase-3 inhibitor Ac-DEVD-CHO group (group CI). Intra-abdominal infection was induced by CLP. Ac-DEVD-CHO 4 μg/g was infused subcutaneously 30 min before CLP in group CI. Five mice in each group were sacrificed after collection of blood samples at 6, 12 and 24 h after CLP. The levels of serum blood urea nitrogen (BUN) and creatinine (Cr)were detected. The apoptosis rate and expression of caspase-3 protein and caspase-3 mRNA were determined.Pathological changes in renal tissues were observed with light microscope. Results The serum BUN and Cr concentratiors, apoptosis rate and expression of caspase-3 mRNA and caspase-3 protein were significantly higher in group CLP than in group S, but lower in group CI than in group CLP ( P ＜ 0.05). Light microscopic examination showed that the pathologic changes induced by Ac-DEVD-CHO were less severe in group CI than in group CLP.Conclusion The renal cell apoptosis is one of the mechanism of AKI induced by sepsis.

Background and purpose:It was reported that zinc ifnger protein 139 (ZNF139) was expressed aberrantly in gastric cancer. But the relationship between ZNF139 and multidrug resistance (MDR) of gastric cancer is still not clear. The purpose of this research was to investigate the expressions and signiifcance of ZNF139, MRP-1, MDR1/P-gp, GST-π in human gastric carcinoma cell lines SGC7901 and SGC7901/ADR. Methods: The expressions of ZNF139, MRP-1, MDR1/P-gp, GST-πwere determined with RT-PCR and Western blot in SGC7901 and SGC7901/ADR cell lines. Then siRNA recombinant plasmid of targeting ZNF139 gene was constructed and imported into gastric cancer cell line SGC7901/ADR, and the expressions of MRP-1, MDR1/P-gp, GST-πwere tested simultaneously. Results:The expressions of ZNF139, MRP-1, MDR1/P-gp, GST-πwere higher in SGC7901/ADR than in SGC7901(P<0.05). ZNF139 was inhibited obviously after siRNA-ZNF139 was transfected into SGC7901/ADR, and expression of MRP-1, MDR1/P-gp, GST-πdecreased(P<0.05). Conclusion:ZNF139 may be invovled in multidrug resistance (MDR) of gastric cancer by up-regulating MRP-1, MDR1/P-gp and GST-π.

Objective:To investigate the effect of tumor deposits on the prognosis and lymph node staging in patients with gastric cancer.Methods:The clinicopathological data of 907 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from Jan to Dec 2016 were retrospectively analyzed. According to the pathological diagnosis, the patients were divided into tumor deposits positive group (121 cases) and tumor deposits negative group (786 cases), and the relationship between tumor deposits and clinicopathological features and prognosis was analyzed.Results:Tumor deposits were found in 121 patients among 907 cases. Univariate analysis showed that tumor deposits were correlated with pT stage, pN stage, pTNM stage, tumor diameter, nerve invasion and vascular invasion (all P<0.05). Multivariate analysis showed that pT stage ( P<0.001), pN stage ( P=0.002), pTNM stage ( P=0.001), tumor diameter ( P=0.033),nerve invasion ( P=0.017), vascular invasion ( P=0.011) were the independent influencing factors of positive tumor deposits. The prognosis of patients with tumor deposits was worse than those without ( χ2=77.869, P<0.001). By univariate analysis, age, tumor location, size, pT stage, pN stage, pTNM stage, tumor thrombus, nerve invasion, tumor deposits and number affected prognosis (all P<0.05). Multivariate analysis showed that age, pT stage, pN stage, pTNM stage, nerve invasion, vascular invasion and the number of tumor deposits were independent prognostic factors (all P<0.05). By stratified analysis tumor deposits were found to have statistical difference in N0~N3a stage (all P<0.05). Conclusion:Tumor deposits is an independent risk factor affecting the prognosis of gastric cancer patients.

OBJECTIVETo discuss the effect of modified double tracks anastomosis in patients with type Siewert II-III( adenocarcinoma of the esophagogastric junction(AEG) treated with radical gastrectomy.

METHODSClinical data of 763 patients with type Siewert II-III AEG undergoing radical operation in our department from January 2004 to December 2008 were analyzed retrospectively. Patients were randomized into 3 groups according to the different procedures modes: radical proximal gastrectomy with modified double tracks anastomosis(266 cases), radical proximal gastrectomy with esophageal gastric stump end-to-side anastomosis(252 cases), and radical total gastrectomy with esophageal jejunum Roux-en-Y anastomosis(245 cases). There were no significant differences in general information and biological characteristics among the 3 groups(all P>0.05). Radical degree, safety, quality of life and prognosis were compared among 3 groups.

RESULTSThere were no significant differences in postoperative complications among the three groups(P>0.05). Six months after operation, in modified double tracks anastomosis group, food intake recovery percentage was superior to the other two groups, and the Visick scores and endoscopic grading were better than esophageal gastric stump end-to-side anastomosis group(all P<0.05). There was no significant difference in recurrent rate of gastric stump between modified double tracks anastomosis group and esophageal gastric stump end-to-side anastomosis group(P>0.05). The 5-year overall survival rate of these 3 groups was 48.7%, 46.3% and 50.2% respectively, and no significant difference was found(all P>0.05).

CONCLUSIONModified double tracks anastomosis is an ideal surgical method for type II-III AEG.

Adenocarcinoma ; Anastomosis, Roux-en-Y ; Esophageal Neoplasms ; Esophagogastric Junction ; Gastrectomy ; Gastric Stump ; Humans ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms ; Survival Rate

OBJECTIVETo screen and identify the proteins related with tumor metastasis of gastric cancer in a nude mouse model bearing orthotopic transplanted tumor.

METHODSZinc finger protein 139 (ZNF139)-specific siRNA was synthesized and transfected into gastric cancer cell line SGC7901, which was then screened by G418. ZNF139-siRNA-transfected cells, negative plasmid-transfected cells and untreated SGC7901 cells were orthotopically transplanted separately on the stomach wall of BALB/c nude mice. The primary tumors and metastatic lymph nodes were harvested to separate the proteins by 2-D fluorescence difference gel electrophoresis (2-D DIGE); after gel digestion, the differential proteins were subjected to liquid chromatography-mass spectrometry (LC-MS) for identification and their functions were analyzed. Western blotting was performed to verify the identified proteins.

RESULTSZNF139 expression was effectively inhibited in siRNA-transfected SGC7901 cells. ZNF139-siRNA-transfected cells showed obviously suppressed tumor growth with a lowered lymph node metastasis rate in nude mice compared with untreated cells and the negative control cells (P<0.05). Proteomic study with 2-D DIGE showed that fascin and hnRNPA2/B1 were down-regulated while ANXA1 was up-regulated in the primary tumors, and ANXA5 was down-regulated in the metastatic lymph nodes in ZNF139-siRNA-transfected group. Western blotting confirmed the results of proteomic analysis.

CONCLUSIONZNF139 gene may promote lymph node metastasis of gastric cancer by regulating fascin, hnRNPA2/B1, ANXA1, and ANXA5.

Animals ; Annexins ; metabolism ; Blotting, Western ; Cell Line, Tumor ; Chromatography, Liquid ; Electrophoresis, Gel, Two-Dimensional ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B ; metabolism ; Humans ; Kruppel-Like Transcription Factors ; metabolism ; Lymphatic Metastasis ; Mice ; Mice, Nude ; Neoplasm Proteins ; metabolism ; Neoplasm Transplantation ; Proteomics ; RNA, Small Interfering ; Stomach Neoplasms ; pathology ; Transfection

Objective To investigate the expression of TIP 30 protein in gastric cancer tissues,and effect of TIP30 over-expression on migration and invasion of gastric cancer cell line SGC7901.Methods Immunohistochemistry streptavid-in-peroxidase (SP) methods were used to detect the expression levels of TIP30 in 93 cases of gastric cancer tissues.Previously constructed pcDNA3.1-TIP30 plasmid were transiently transfected into SGC7901 cells.The proliferation of cells were detected by using MTT assay when TIP30 was overexpressed.Transwell assay to determine migration and invasion ability of SGC7901.Western blot was used to examine the changes of concentration of E-cadherin,N-cadherin and MMP9.Results The positive expression rate of TIP30 was 39％ significantly lower in gastric cancer tissues than 92％ in normal gastric mucosa tissues (x2 =32.68,P ＜ 0.05),there was a significant correlation between reduced expression of TIP30 and depth of infiltration,including nodal metastasis,TNM stage (x2 =3.535,7.421,6.754,all P ＜ 0.05);MTT showed that the proliferation of SGC7901 cells in the pcDNA3.1-TIP30 transfected group significantly decreased when TIP30 was overexpressed at respective time of 72,96 hours (t =6.528,7.249,both P ＜ 0.05),Transwell assay showed that overexpression of TIP30 significantly decreased migratory and invasive numbers of SGC7901 cells (t =5.769,P ＜ 0.05;t =7.886,P ＜ 0.05);the expression level of MMP-9 and N-cadherin in TIP30 overexpressing cells group significantly decreased (t =9.811,10.362,both P ＜ 0.05),mean while E-cadherin expression was significantly higher than before (t =6.137,P ＜ 0.05).Conclusion TIP30 protein is low expressed in gastric cancer and the overexpression of TIP30 inhibits the proliferation,migration and invasion of gastric cell line SGC7901.

Objective: To explore the clinical significance of laparoscopic exploration combined with abdominal exfoliative cytology in the diagnosis and treatment of patients with locally advanced gastric cancer. Methods: Inclusion criteria: (1) cancer confirmed by gastroscopy and pathology without preoperative anti-tumor treatment; (2) no distant metastases found in preoperative imaging examinations; (3) patients without surgical contraindications and being tolerant to surgery; (4) patients were willing to undergo laparoscopic exploration and abdominal exfoliative cytology examination, and signed informed consent. A retrospective cohort study method was used to collect and analyze the clinicopathological data of 225 patients with advanced gastric cancer based on the above inclusion criteria from a prospective, multicenter, open, randomized controlled phase III clinical trial (registration No. NCT01516944) conducted between February 2012 and December 2018 in The Fourth Hospital of Hebei Medical University, including 162 males and 63 females with age ranged from 23 to 78 years old. Forty-five patients (20.0%) were classified as Borrmann type I to II, and 180 (80.0%) were classified as type III to IV. All the patients underwent laparoscopy and peritoneal lavage cytology under general anesthesia. Laparoscopic exploration sequence: left and right diaphragm→liver and spleen→parietal peritoneum→pelvic cavity→greater omentum, small intestine, mesentery→transverse colon mesentery →stomach. Contents of exploration: (1) with or without ascites; (2) whether metastatic lesions existed in the peritoneum, mesentery, omentum and Douglas pouch; (3) whether metastasis existed on the liver surface; (4) whether the gastric lymph nodes were swollen; (5) whether infiltration occurred on the gastric serosa surface; (6) whether gastric wall was stiff. The left and right subphrenic, the abdominal and pelvic peritoneum, and the mesentery were rinsed with 500 ml of sterilized normal saline. Position of the reverse Trendelenburg was used in the Douglas pouch. The peritoneal lavage fluid under the liver and spleen fossa was collected. Cytological examination was carried out for exfoliative tumor cells. Evaluation criteria: (1) peritoneal metastasis (P): P0 meant no peritoneal metastasis, P1 meant peritoneal metastasis; (2) free peritoneal cancer cells (CY): CY0 meant no cancer cells in peritoneal lavage fluid cytology, CY1 meant cancer cells in peritoneal lavage fluid cytology. The results of patients undergoing laparoscopic exploration combined with abdominal exfoliative cytology, treatment options and prognosis were analyzed. Kaplan-Meier method was used to calculate the survival rate and a survival curve was drawn. Log-rank test was used for survival analysis. Results: After laparoscopic exploration in 225 patients, clinical staging was corrected in 68 (30.2%) patients, of whom 7 (3.1%) downstaged and 61 (27.1%) increased in staging. Of 164 patients evaluated as P0CY0 after the first laparoscopy and peritoneal cytology examination, 126 underwent radical D2 surgery, and the other 38 patients were found to have later local lesions or extensive fusion of local lymph nodes, so then received neoadjuvant chemotherapy. Twenty-nine patients evaluated as P1CY0 or P1CY1 and 32 patients as P0CY1 underwent intraperitoneal hyperthermic chemotherapy+conversion therapy, and then a second laparoscopic exploration was performed to determine the treatment plan. In total, the original treatment regimens were changed after laparoscopic exploration in 99(44.0%) cases. The follow-up period ended in January 2019. The overall 2-year survival rate of 225 patients was 64.0%. As for those who were evaluated as P0CY0, P0CY1 and P1CY0-1 after the first laparoscopic exploration, the 2-year overall survival rate was 70.7%, 65.6% and 24.1%, respectively (P=0.002). The stratified analysis showed that among 180 patients with stage III tumor, after laparoscopic exploration combined with abdominal exfoliative cytology, 125 patients were found to be P0CY0, 28 were P0CY1, and 27 were P1CY0-1, whose 2-year overall survival rates were 70.4%, 64.3%, and 29.6% respectively, and the difference among these 3 groups was statistically significant (P=0.009). Conclusion Laparoscopic exploration combined with abdominal exfoliative cytology in patients with locally advanced gastric cancer has important clinical guiding significance in improving accurate staging, treatment options and prognosis evaluation, and can avoid non-therapeutic open-close abdominal surgery.