Objective·To explore the expression of sorting nexin 1(SNX1)in colorectal cancer(CRC)and its impact on the proliferation and migration of CRC cells.Methods·Transcriptomic data and clinical pathological information of CRC were obtained from The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx),and Gene Expression Omnibus(GEO)databases for enrichment analysis with Gene Set Enrichment Analysis(GSEA)software.The expression of SNX1 in CRC tissues and cells was detected by quantitative real-time polymerase chain reaction(qPCR),Western blotting,and immunohistochemistry staining(IHC).Small interfering RNA(siRNA)was used to knock down the expression of SNX1 to observe its effect on tumor cell proliferation and migration.Correlation analysis was conducted to explore the potential molecular mechanisms underlying SNX1-mediated CRC cell migration,and mRNA level validation was performed in SNX1 knockdown cell lines.Results·Analysis of CRC patients data in TCGA and tissue microarrays revealed that SNX1 expression was downregulated in CRC tissues and correlated with tumor diameter and distant metastasis.Knockdown of SNX1 enhanced tumor cell proliferation and migration.The expression of SNX1 was negatively correlated with metastasis associated in colon cancer 1(MACC1),mesenchymal to epithelial transition factor(MET),and Notch;knockdown of SNX1 led to upregulation of these genes.Silencing SNX1 resulted in the downregulation of the epithelial marker cadherin 1(CDH1)and the upregulation of vimentin(VIM)and Snail family transcriptional repressor 1(SNAI1).Conclusion·SNX1 expression was significantly downregulated in CRC tissues and correlated with patient prognosis.Low expression of SNX1 enhanced the proliferation and migration of CRC cells and was associated with the MACC1-MET pathway and EMT.SNX1 may serve as a potential biomarker for poor prognosis and a novel therapeutic target in CRC.

Objective:To investigate the expression of FGD6(FYVE,RhoGEF,and PH domain containing 6)in lung adenocarcinoma(LUAD)tissues and explore its impact on LUAD cells proliferation,apoptosis,migration,invasion,and the possible mechanism.Methods:By searching bioinformatics websites and databases,the differences in the expression of FGD6 gene in LUAD,paracancerous tissues and normal lung tissues were analyzed,and further analyzed the correlation between the expression of FGD6 and the survival prognosis of LUAD patients as well as the correlation with the clinicopathological features of LUAD patients.Two different siRNAs(si-FGD6-1,si-FGD6-2)targeting FGD6 gene were transfected into LUAD cell lines(A549 and NCI-H23)using lipofection.The knockdown efficiency of the siRNAs was detected by real-time fluorescence quantitative PCR and Western blotting.CCK-8 assay,clone formation assay and FCM assay were used to detect the effects of silencing FGD6 expression on the proliferation and apoptosis of A549 and NCI-H23 cells;Wound healing assay assay and Transwell assay were used to detect the effects of silencing FGD6 expression on the migratory and invasive ability of A549 and NCI-H23 cells.Subsequently,Gene Set Enrichment Analysis(GESA)was performed based on the transcriptome data of LUAD patients in The Cancer Genome Atlas(TCGA)database,and it was hypothesized that FGD6 might regulate the Hippo signaling pathway in LUAD cells.Real-time fluorescence quantitative PCR and Western blotting were used to detect the effects of silencing FGD6 expression on the connective tissue growth factor(CTGF)and cysteine-rich 61(CYR61)genes and the phosphorylation of the Hippo signaling pathway downstream in LUAD cells.The effect of the expression level of phosphorylated Yes-associated protein(YAP)in the Hippo signaling pathway.Results:Database analysis showed that FGD6 expression was up-regulated in a variety of tumors,and the expression level in LUAD was significantly higher than that in normal tissues(P<0.001).The overall survival time of patients with high expression of FGD6 was less than that of those with low expression(P<0.05),and it was positively correlated with the clinical stage and lymph node metastatic status of LUAD patients.After knocking down FGD6 expression,the expression levels of FGD6 mRNA and protein in A549 and NCI-H23 cells were significantly down-regulated,and their cell proliferation,anti-apoptosis,migration and invasion abilities were significantly reduced(all P<0.01).The results of real-time fluorescence quantitative PCR showed that knockdown of FGD6 expression led to significant down-regulation of the expression levels of CTGF and CYR61 mRNA,the downstream targeting factors of the Hippo signaling pathway(both P<0.01),while the results of Western blotting showed that the expression levels of phosphorylated Yes-associated protein(p-YAP)were significantly down-regulated in the Hippo signaling pathway(P<0.01).Conclusion:FGD6 is highly expressed in LUAD tissues,and its high expression is associated with poor prognosis.Knockdown of FGD6 gene can inhibit LUAD cells proliferation,apoptosis,migration and invasion,and activate the Hippo pathway,suggesting its potential as a therapeutic target in LUAD.

Objective:To evaluate the efficacy and safety of high-dose injectable dexlansoprazole in the treatment of acute upper gastrointestinal ulcer hemorrhage.Methods:This study was a randomized, double-blind, positive drug parallel controlled, multicenter clinical trial led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), with participation from 43 hospitals such as Yichun People′s Hospital, Army Medical Center of PLA (Chongqing Daping Hospital), etc. From August 31, 2019 to May 25, 2020, 346 patients with upper gastrointestinal hemorrhage caused by acute gastric and (or) duodenal ulcer were selected. The subjects were randomly divided into experimental group and control group according to a 2 to 1 stratification scheme using the SAS 9.4 software. The medication regimen for the experimental group was intravenous injection of dexlansoprazole 30 mg/times, once every 12 h, while the medication regimen for the control group was intravenous injection of lansoprazole and dexlansoprazole mimetics, 30 mg/times, once every 12 h; the treatment course was 5 days. The primary efficacy indicator (72 h effective hemostasis rate), the secondary efficacy indicator(clinical hemostasis rate at 24, 48, and 120 h, and the proportion of subjects who underwent endoscopic treatment or surgical procedures again due to hemorrhage within 5 days), and the incidence of adverse reactions were compared between the 2 groups. Binomial distribution normal approximation method was performed to calculate the 95% confidence interval (95% CI) of the difference in hemostasis rate between the experimental group and the control group. Fisher′s exact test was used for statistical analysis. Results:A total of 329 patients (219 cases in the experimental group and 110 cases in the control group) were enrolled. The 72 h effective hemostasis rate (95% CI) of the experimental and control group was 95.9%(210/219, 92.3% to 98.1%) and 93.6%(103/110, 87.3% to 97.4%), respectively, and the difference was not statistically significant ( P>0.05). The difference in the 72-hour effective hemostasis rate(95% CI) between the experimental and the control group was 2.3% (-3.0% to 7.5%). The clinical hemostasis rates at 24, 48, and 120 h of the treatment were 82.2% (176/214), 99.1%(210/212), and 100.0%(210/210) in the experimental group, and 85.2%(92/108), 98.1%(104/106), and 100.0%(105/105) in the control group, respectively, and the differences were not statistically significant (all P>0.05). The proportion of subjects who underwent endoscopic treatment and surgical procedure again within 5 days (95% CI)of the experimental group and control group was 0 (0 to 1.7%) and 1.9% (0.2% to 6.5%), respectively, and the difference was not statistically significant ( P>0.05). The result of safety evaluation showed that the overall incidence of adverse reactions of the experimental group and the control group was 6.4% (14/219) and 11.8% (13/110), respectively, and the difference was not statistically significant ( P>0.05). Conclusion:High dose injectable dexlansoloprazole is an effective and safe treatment for upper gastrointestinal ulcer hemorrhage, and suitable for clinical application.

Objective:To investigate the expression of FGD6(FYVE,RhoGEF,and PH domain containing 6)in lung adenocarcinoma(LUAD)tissues and explore its impact on LUAD cells proliferation,apoptosis,migration,invasion,and the possible mechanism.Methods:By searching bioinformatics websites and databases,the differences in the expression of FGD6 gene in LUAD,paracancerous tissues and normal lung tissues were analyzed,and further analyzed the correlation between the expression of FGD6 and the survival prognosis of LUAD patients as well as the correlation with the clinicopathological features of LUAD patients.Two different siRNAs(si-FGD6-1,si-FGD6-2)targeting FGD6 gene were transfected into LUAD cell lines(A549 and NCI-H23)using lipofection.The knockdown efficiency of the siRNAs was detected by real-time fluorescence quantitative PCR and Western blotting.CCK-8 assay,clone formation assay and FCM assay were used to detect the effects of silencing FGD6 expression on the proliferation and apoptosis of A549 and NCI-H23 cells;Wound healing assay assay and Transwell assay were used to detect the effects of silencing FGD6 expression on the migratory and invasive ability of A549 and NCI-H23 cells.Subsequently,Gene Set Enrichment Analysis(GESA)was performed based on the transcriptome data of LUAD patients in The Cancer Genome Atlas(TCGA)database,and it was hypothesized that FGD6 might regulate the Hippo signaling pathway in LUAD cells.Real-time fluorescence quantitative PCR and Western blotting were used to detect the effects of silencing FGD6 expression on the connective tissue growth factor(CTGF)and cysteine-rich 61(CYR61)genes and the phosphorylation of the Hippo signaling pathway downstream in LUAD cells.The effect of the expression level of phosphorylated Yes-associated protein(YAP)in the Hippo signaling pathway.Results:Database analysis showed that FGD6 expression was up-regulated in a variety of tumors,and the expression level in LUAD was significantly higher than that in normal tissues(P<0.001).The overall survival time of patients with high expression of FGD6 was less than that of those with low expression(P<0.05),and it was positively correlated with the clinical stage and lymph node metastatic status of LUAD patients.After knocking down FGD6 expression,the expression levels of FGD6 mRNA and protein in A549 and NCI-H23 cells were significantly down-regulated,and their cell proliferation,anti-apoptosis,migration and invasion abilities were significantly reduced(all P<0.01).The results of real-time fluorescence quantitative PCR showed that knockdown of FGD6 expression led to significant down-regulation of the expression levels of CTGF and CYR61 mRNA,the downstream targeting factors of the Hippo signaling pathway(both P<0.01),while the results of Western blotting showed that the expression levels of phosphorylated Yes-associated protein(p-YAP)were significantly down-regulated in the Hippo signaling pathway(P<0.01).Conclusion:FGD6 is highly expressed in LUAD tissues,and its high expression is associated with poor prognosis.Knockdown of FGD6 gene can inhibit LUAD cells proliferation,apoptosis,migration and invasion,and activate the Hippo pathway,suggesting its potential as a therapeutic target in LUAD.

Objective:To evaluate the efficacy and safety of high-dose injectable dexlansoprazole in the treatment of acute upper gastrointestinal ulcer hemorrhage.Methods:This study was a randomized, double-blind, positive drug parallel controlled, multicenter clinical trial led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), with participation from 43 hospitals such as Yichun People′s Hospital, Army Medical Center of PLA (Chongqing Daping Hospital), etc. From August 31, 2019 to May 25, 2020, 346 patients with upper gastrointestinal hemorrhage caused by acute gastric and (or) duodenal ulcer were selected. The subjects were randomly divided into experimental group and control group according to a 2 to 1 stratification scheme using the SAS 9.4 software. The medication regimen for the experimental group was intravenous injection of dexlansoprazole 30 mg/times, once every 12 h, while the medication regimen for the control group was intravenous injection of lansoprazole and dexlansoprazole mimetics, 30 mg/times, once every 12 h; the treatment course was 5 days. The primary efficacy indicator (72 h effective hemostasis rate), the secondary efficacy indicator(clinical hemostasis rate at 24, 48, and 120 h, and the proportion of subjects who underwent endoscopic treatment or surgical procedures again due to hemorrhage within 5 days), and the incidence of adverse reactions were compared between the 2 groups. Binomial distribution normal approximation method was performed to calculate the 95% confidence interval (95% CI) of the difference in hemostasis rate between the experimental group and the control group. Fisher′s exact test was used for statistical analysis. Results:A total of 329 patients (219 cases in the experimental group and 110 cases in the control group) were enrolled. The 72 h effective hemostasis rate (95% CI) of the experimental and control group was 95.9%(210/219, 92.3% to 98.1%) and 93.6%(103/110, 87.3% to 97.4%), respectively, and the difference was not statistically significant ( P>0.05). The difference in the 72-hour effective hemostasis rate(95% CI) between the experimental and the control group was 2.3% (-3.0% to 7.5%). The clinical hemostasis rates at 24, 48, and 120 h of the treatment were 82.2% (176/214), 99.1%(210/212), and 100.0%(210/210) in the experimental group, and 85.2%(92/108), 98.1%(104/106), and 100.0%(105/105) in the control group, respectively, and the differences were not statistically significant (all P>0.05). The proportion of subjects who underwent endoscopic treatment and surgical procedure again within 5 days (95% CI)of the experimental group and control group was 0 (0 to 1.7%) and 1.9% (0.2% to 6.5%), respectively, and the difference was not statistically significant ( P>0.05). The result of safety evaluation showed that the overall incidence of adverse reactions of the experimental group and the control group was 6.4% (14/219) and 11.8% (13/110), respectively, and the difference was not statistically significant ( P>0.05). Conclusion:High dose injectable dexlansoloprazole is an effective and safe treatment for upper gastrointestinal ulcer hemorrhage, and suitable for clinical application.

Objective To investigate blood glucose,HbA1c and GA levels in patients with acute cerebral infarction.Methods 129 patients with acute cerebral infarction and 102 healthy persons were recruited.Blood glucose,HbA1c and GA levels were com-pared between acute infarction patients and healthy people.The correlation of blood glucose,HbA1c and GA with different degree of neurological deficits,number and sizes of infarct lesions and prognosis were explored.Results Fasting plasma glucose,HbA1c and GA levels in patients with acute cerebral infarction were significantly higher than in healthy people(P <0.05).GA and HbA1c levels were higher in patients with more severe degree of neurological deficit,larger infarct volume and poorer prognosis,and the differences were statistically significant (P <0.05).GA level was significantly higher in patients with multifocal infraction than pa-tients with single(P <0.05),however,there were no differences of HbA1c between the two groups.No significantly differences of fasting blood glucose were found among the patients classified with neurological deficit,number and sizes of infarct lesion and prog-nosis(P >0.05).Conclusion Blood glucose,HbA1c and GA levels were closely related with neurological deficit,severity and prog-nosis of acute cerebral infarction,thus determination of these indicators is of important clinical significance.