BACKGROUND: The results of studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) reconstruction on the quality of life (QoL) are still inconsistent. The aim of this trial was to compare the long-term QoL of B-I with R-Y anastomosis after curative distal gastrectomy for gastric cancer. METHODS: A total of 140 patients undergoing curative distal gastrectomy with D2 lymphadenectomy in West China Hospital, Sichuan University from May 2011 to May 2014 were randomly assigned to the B-I group ( N  = 70) and R-Y group ( N  = 70). The follow-up time points were 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after the operation. The final follow-up time was May 2019. The clinicopathological features, operative safety, postoperative recovery, long-term survival as well as QoL were compared, among which QoL score was the primary outcome. An intention-to-treat analysis was applied. RESULTS: The baseline characteristics were comparable between the two groups. There were no statistically significant differences in terms of postoperative morbidity and mortality rates, and postoperative recovery between the two groups. Less estimated blood loss and shorter surgical duration were found in the B-I group. There were no statistically significant differences in 5-year overall survival (79% [55/70] of the B-I group vs. 80% [56/70] of the R-Y group, P  = 0.966) and recurrence-free survival rates (79% [55/70] of the B-I group vs. 78% [55/70] of the R-Y group, P  = 0.979) between the two groups. The scores of the global health status of the R-Y group were higher than those of the B-I group with statistically significant differences (postoperative 1 year: 85.4 ± 13.1 vs . 88.8 ± 16.1, P  = 0.033; postoperative 3 year: 87.3 ± 15.2 vs . 92.8 ± 11.3, P  = 0.028; postoperative 5 year: 90.9 ± 13.7 vs . 96.4 ± 5.6, P  = 0.010), and the reflux (postoperative 3 year: 8.8 ± 12.9 vs . 2.8 ± 5.3, P  = 0.001; postoperative 5 year: 5.1 ± 9.8 vs . 1.8 ± 4.7, P  = 0.033) and epigastric pain (postoperative 1 year: 11.8 ± 12.7 vs. 6.1 ± 8.8, P  = 0.008; postoperative 3 year: 9.4 ± 10.6 vs. 4.6 ± 7.9, P  = 0.006; postoperative 5 year: 6.0 ± 8.9 vs . 2.7 ± 4.6, P  = 0.022) were milder in the R-Y group than those of the B-I group at the postoperative 1, 3, and 5-year time points. CONCLUSIONS: Compared with B-I group, R-Y reconstruction was associated with better long-term QoL by reducing reflux and epigastric pain, without changing survival outcomes. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-10001434.
Humans ; Stomach Neoplasms/pathology* ; Anastomosis, Roux-en-Y/methods* ; Quality of Life ; Treatment Outcome ; Gastrectomy/methods* ; Postoperative Complications ; Gastroenterostomy/methods* ; Pain

Humans ; Female ; Breast Neoplasms/pathology* ; Retrospective Studies ; Prognosis ; Stomach Neoplasms/pathology* ; China/epidemiology*

Objective: To explore whether hsa_circ_0000670 promotes the progression of gastric cancer by regulating the miR-515-5p/SIX1 molecular axis. Methods: The gastric cancer and adjacent normal tissues of 35 gastric cancer patients admitted to Rugao Hospital Affiliated to Nantong University from 2014 to 2015 were collected. The expression levels of circ_0000670, miR-515-5p and Sine oculis homeobox 1 (SIX1) in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The correlations between circ_0000670 and miR-515-5p, miR-515-5p and SIX1, circ_0000670 and SIX1 were analyzed by the Pearson method. Patients were divided into low circ_0000670 expression group (17 cases) and high circ_0000670 expression group (18 cases) based on the median of circ_0000670 expression level, and Kaplan-Meier was used to analyze the 5-year survival of patients. Cell proliferation was assessed via clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. Wound healing and Transwell assays were used to detect cell migration and invasion ability. The targeting relationship between miR-515-5p and circ_0000670 or SIX1 was confirmed by the dual luciferase reporter assay. Nude mice were injected into HGC-27 cells transfected with sh-NC or sh-circ_0000670, and the volume and weight of the transplanted tumor were measured, also, the levels of circ_0000670, miR-515-5p and SIX1 in the transplanted tumor tissue were detected. Results: The expression levels of circ_0000670 and SIX1 in gastric cancer tissues and cell lines were significantly increased (P<0.05), while the expression levels of miR-515-5p were significantly decreased (P<0.05). The survival rate of patients in the low circ_0000670 expression group (82.4%) was significantly higher than that in the high circ_0000670 expression group (28.7%, P=0.034). Circ_0000670 was negatively correlated with miR-515-5p (r=-0.846, P<0.001), and miR-515-5p was negatively correlated with SIX1 (r=-0.615, P<0.001), but circ_0000670 was positively correlated with SIX1 (r=0.814, P<0.001). Transfection of si-circ_0000670 or miR-515-5p mimic could significantly reduce the number of clone-forming cells, migration distance, migration and invasion cells (P<0.05), and increase the ratio of G(0)/G(1) phase cells, apoptosis rate and the protein level of E-cadherin (P<0.05), decreased the proportion of S-phase cells and the protein level of Vimentin (P<0.05). The dual luciferase report assay confirmed that circ_0000670 could target miR-515-5p, and miR-515-5p could bind to SIX1. Co-transfection of si-circ_0000670 and miR-515-5p inhibitor could significantly attenuate the effects of si-circ_0000670 on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Co-transfection of miR-515-5p mimic and pcDNA-SIX1 could significantly reduce the effects of miR-515-5p mimic on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Compared with the sh-NC group [volume=(596.20±125.46) mm(3) and weight=(538.00±114.39) g], the volume and weight of transplanted tumors in the sh-circ_0000670 group [volume=(299.20±47.58) mm 3 and weight=(289.80±48.73 g)] were significantly reduced (P<0.05), the expression levels of circ_0000670 and SIX1 were significantly reduced (P<0.05), and the expression level of miR-515-5p was significantly increased (P<0.05). Conclusion: Knockdown of circ_0000670 could inhibit cell proliferation, migration, invasion of gastric cancer cells, induce cell cycle arrest in G(0)/G(1) phase and promote cell apoptosis by regulating the miR-515-5p/SIX1 axis.
Animals ; Mice ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Mice, Nude ; MicroRNAs/genetics* ; Stomach Neoplasms/genetics*

OBJECTIVE: To observe the clinical effect of acupuncture for functional delayed gastric emptying after gastric cancer surgery on the basis of routine treatment. METHODS: A total of 80 patients with functional delayed gastric emptying after gastric cancer surgery were randomly divided into an observation group (40 cases, 3 cases dropped off) and a control group (40 cases, 1 case dropped off). The control group was treated with routine treatment, e.g. continuous gastrointestinal decompression. On the basis of the treatment in the control group, the observation group was treated with acupuncture at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Gongsun (SP 4), Sanyinjiao (SP 6), 30 min each time, once a day, 5 days as a course, 1-3 courses were required. The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay were compared in the two groups, and the clinical effect was evaluated. RESULTS: The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay in the observation group were shorter than the control group (P<0.001). CONCLUSION On the basis of routine treatment, acupuncture could accelerate the recovery of patients with functional delayed gastric emptying after gastric cancer surgery.
Humans ; Stomach Neoplasms ; Gastroparesis ; Acupuncture Therapy ; Acupuncture Points

OBJECTIVE: To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis. METHODS: A total of 1,490 cancer patients (lung/gastric/liver/: 550/460/480) and 800 controls were recruited in this case-control study. The meta-analysis was performed by pooling the data from previous related studies and the present study. RESULTS: The results of this study showed that in the Hubei Han Chinese population, the rs10754339 gene was significantly associated with the risk of lung and gastric cancer but not liver cancer, and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer. The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339 and breast cancer risk, as well as between rs12976445 and lung cancer risk. CONCLUSION The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population, which should be validated in future studies with larger sample sizes in other ethnic populations.
Humans ; MicroRNAs/genetics* ; Stomach Neoplasms/genetics* ; Case-Control Studies ; Lung Neoplasms/genetics* ; Risk

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and β diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and β diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.
Humans ; Isobutyrates ; Gastrointestinal Microbiome ; Quality of Life ; Stomach Neoplasms/therapy* ; Immunotherapy ; Treatment Outcome

Objective To investigate the impacts of forkhead box M1(FOXM1)on the proliferation,invasion,and drug resistance of gastric cancer cells by regulating the circular RNA circ_NOTCH1.Methods Western blotting and real-time quantitative PCR were performed to determine the expression of FOXM1 protein and circ_NOTCH1,respectively,in the gastric cancer tissue,para-carcinoma tissue,human normal gastric mucosa epithelial cell line GES-1 and gastric cancer cell lines MGC-803,HGC-27,and BGC-823.BGC-823 cells were classified into the following groups:control,short hairpin RNA FOXM1(sh-FOXM1)and negative control(sh-NC),small interfering RNA circ_NOTCH1(si-circ_NOTCH1)and negative control(si-NC),and sh-FOXM1+circ_NOTCH1 overexpression plasmid(sh-FOXM1+pcDNA-circ_NOTCH1)and sh-FOXM1+negative control(sh-FOXM1+pcDNA).CCK-8 assay and clone formation assay were employed to measure the cell proliferation,and Transwell assay to measure cell invasion.After treatment with 1.0 mg/L adriamycin for 48 h,the cell resistance in each group was analyzed.Western blotting was employed to determine the expression levels of FOXM1,proliferating cell nuclear antigen(PCNA),Bax,multi-drug resistance-associated protein 1(MRP1),and multi-drug resistance gene 1(MDR1).RNA pull-down and RNA immunoprecipitation were employed to examine the binding of circ_NOTCH1 to FOXM1 protein.Results Compared with those in the para-carcinoma tissue,the expression levels of FOXM1 protein and circ_NOTCH1 in the gastric cancer tissue were up-regulated(all P<0.001).Compared with GES-1 cells,MGC-803,HGC-27,and BGC-823 cells showed up-regulated expression levels of FOXM1 protein and circ_NOTCH1(all P<0.001).Compared with the control group and sh-NC group,the sh-FOXM1 group with down-regulated expression of FOXM1 protein and circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with the control group and the si-NC group,the si-circ_NOTCH1 group with down-regulated expression of circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with sh-FOXM1 group and sh-FOXM1+pcDNA group,the sh-FOXM1+pcDNA-circ_NOTCH1 group with up-regulated expression of circ_NOTCH1 showed increased optical density value,clone formation rate,cell invasion number,and cell viability,up-regulated expression of PCNA,MRP1,and MDR1,and down-regulated expression of Bax protein(all P<0.001).FOXM1 protein was able to interact with circ_NOTCH1.Conclusion Interference with FOXM1 may inhibit the proliferation,invasion,and drug resistance of gastric cancer cells by silencing circ_NOTCH1 expression.
Humans ; bcl-2-Associated X Protein/metabolism* ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Drug Resistance ; Forkhead Box Protein M1/metabolism* ; Gene Expression Regulation, Neoplastic ; MicroRNAs/genetics* ; Proliferating Cell Nuclear Antigen/metabolism* ; Receptor, Notch1/metabolism* ; RNA, Small Interfering/genetics* ; Stomach Neoplasms/genetics*

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.
Humans ; Stomach Neoplasms/genetics* ; Cyclin D1/metabolism* ; Tumor Suppressor Protein p53 ; Phosphoproteins/metabolism* ; Ki-67 Antigen ; Cell Line, Tumor ; Prognosis ; Cell Proliferation ; Phosphoprotein Phosphatases/metabolism* ; Threonine ; Serine

Objective To investigate the expression and prognostic significance of mediator complex subunit 8 (MED8) in gastric cancer and its impact on the cell cycle.Methods The expression of MED8 in gastric cancer and adjacent tissues and its correlation with patients' prognosis were analyzed using public databases.A validation cohort of 104 patients who underwent radical resection for gastric cancer in the First Affiliated Hospital of Bengbu Medical College from June 2012 to July 2017 was included.The receiver operating characteristic curve was established to evaluate the predictive value of MED8 for postoperative 5-year survival.Bioinformatics tools were used to predict the biological roles of MED8 in gastric cancer.The effect of the MED8 level on the G1/S phase transition of gastric cancer cells (MGC-803) was analyzed via lentivirus transduction and flow cytometry.Western blotting was carried out to assess the impact of MED8 expression on the protein levels of cyclin-dependent kinase 4(Cdk4) and G1/S-specific cyclin-D1(CyclinD1) in MGC-803 cells.Results The high expression of MED8 in the gastric cancer tissue was associated with poor prognosis (P<0.001) and had prognostic significance (area under curve=0.733,P<0.001).Gene enrichment analysis suggested that MED8 may participate in the cell cycle process.Flow cytometry results revealed that the upregulation of MED8 expression promoted the transition of MGC-803 cells from the G1 phase to the S phase (P<0.001),while the downregulation of MED8 had the opposite effect (P<0.001).Western blotting showed increases in the protein levels of Cdk4 and CyclinD1 in MGC-803 cells with upregulated MED8 expression (all P<0.001),and decreases in the cells with downregulated MED8 expression (all P<0.001).Conclusion MED8 is highly expressed in gastric cancer and may affect its progression and prognosis by regulating the G1/S phase transition of gastric cancer cells.
Humans ; Stomach Neoplasms ; Prognosis ; Cell Proliferation ; Cell Cycle ; Mediator Complex/metabolism* ; Cell Line, Tumor

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Tumor Suppressor Protein p53 ; Network Pharmacology ; ErbB Receptors ; Protein Serine-Threonine Kinases ; Serine ; Adenosine Triphosphate ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology*