High expression of death-associated protein 5 promotes glucose metabolism in gastric cancer cells and correlates with poor survival outcomes / 南方医科大学学报

OBJECTIVE@#To investigate the prognostic value of death-associated protein 5 (DAP5) in gastric cancer (GC) and its regulatory effect on aerobic glycolysis in GC cells.@*METHODS@#We analyzed DAP5 expression levels in GC and adjacent tissues and its association with survival outcomes of GC patients using public databases. We collected paired samples of GC and adjacent tissues from 102 patients undergoing radical resection of GC in our hospital from June, 2012 to July, 2017, and analyzed the correlation of DAP5 expression level detected immunohistochemically with the clinicopathological parameters of the patients. Cox regression analysis, Kaplan-Meier analysis, and ROC curves were used to explore the independent risk factors and the predictive value of DAP5 expression for 5-year survival of the patients. In the cell experiments, we observed the changes in aerobic glycolysis in MGC-803 cells following lentivirus-mediated DAP5 knockdown or overexpression by measuring glucose uptake and cellular lactate level and using qRT-PCR and Western blotting.@*RESULTS@#Analysis using the public databases showed that DAP5 was highly expressed in GC and correlated with tumor progression and poor survival outcomes of the patients (P < 0.05). In the clinical samples, DAP5 expression was significantly higher in GC than in the adjacent tissues (3.19±0.60 vs 1.00±0.12; t=36.863, P < 0.01), and a high expression of DAP5 was associated with a reduced 5-year survival rate of the patients (17.6% vs 72.5%; χ2=29.921, P < 0.05). A high DAP5 expression, T3-4, N2-3, and CEA≥5 ng/mL were identified as independent risk factors affecting 5-year survival outcomes of GC (P < 0.05), for which DAP5 expression showed a prediction sensitivity, specificity and accuracy of 73.2%, 80.4% and 79.0%, respectively. In MGC-803 cells, DAP5 knockdown significantly reduced glucose uptake, lactate level and the expressions of GLUT1, HK2 and LDHA, and DAP5 overexpression produced the opposite effects (P < 0.05).@*CONCLUSION@#A high expression of DAP5 in GC, which enhances cellular aerobic glycolysis to promote cancer progression, is correlated with a poor survival outcome and may serve as a biomarker for evaluating long-term prognosis of GC patients.

FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.

Analysis of infection composition and drug resistance to Gram-negative bacilli in children′s respiratory tract in Suzhou from 2007 to 2016 / 中华实用儿科临床杂志

Objective@#To analyze the infection composition and drug resistance to Gram-negative (G-) bacilli in children′s respiratory tract in Suzhou, in order to provide evidence for rational use of antibiotics clinically.@*Methods@#G- bacilli culture samples were collected from 21 561 cases of nasopharyngeal secretions from patients with respiratory tract infection admitted at the Department of Respiratory, Children′s Hospital of Soochow University from January 2007 to December 2016, including 21 246 cases in general wards, and 315 patients who were transferred to the respiratory department after treatment in the Intensive Care Unit(ICU), and the children were divided into the general ward group and the ICU group, and the pathogens were compared and the changes in bacterial susceptibility were dynamically observed between the 2 groups.@*Results@#The primary G-bacteria for respiratory infection was Haemophilus influenzae, followed by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii.The detection rates of Klebsiella pneumoniae and Pseudomonas aeruginosa in the ICU group were 16.8% (21/125 strains)and 14.4%(18/125 strains), respectively, which were significantly higher than those in the general ward group [10.0%(208/2 071 strains), 9.2%(190/2 071 strains)]. The detection rates of G-bacteria in the ICU group were 33.7%(106/315 cases), which were significantly higher than those in the general ward group [9.4%(1 997/21 246 cases)], and the difference was statistically significant(χ2=210.325, P<0.001). The rare G-bacillus such as Stenotrophomonas maltophilia, Acinetobacter junii and Burkholderia onion were higher in the ICU group [17.6%(22/125 strains)] than that in the general ward group [6.4% (132/2 071 strains)]. The rate that of G-bacteria with two or more mixed infection in ICU group [17.0% (18/106 cases)] was significantly higher than in the general ward group [3.4%(68/1 997 cases)], and the difference was statistically significant(χ2=47.3, P<0.05). For the mixed infection, the ICU group was mainly composed of Klebsiella pneumoniae mixed with Pseudomonas aeruginosa or Escherichia coli, while the general ward group was composed of Haemophilus influenzae mixed with Pseudomonas aeruginosa or Escherichia coli.The sensitivity of Haemophilus influenzae to Ampicillin, Sultamicillin, Cefuroxime, Cefaclor and Azithromycin decreased, and the sensitivity to Chloramphenicol, Tetracycline and Trimethoprim+ Sulfamethoxazole increased year by year, and there were statistically significant differences in different years (all P<0.05). The sensiti-vity to Escherichia coli to Ceftazidime decreased year by year, and the sensitivity to Ampicillin and Levofloxacin increased year by year, and there were statistically significant differences in different years (all P<0.05). The sensitivity to Klebsiella pneumoniae to Cefoperazone/Sulbactam and imipenem decreased, and the sensitivity to Ciprofloxacin and Levofloxacin increased, and there were statistically significant differences in different years (all P<0.05). The sensitivity to Pseudomonas aeruginosa, Cefoperazone/Sulbactam and Ceftriaxone decreased year by year, and the sensitivity to Levofloxacin increased, and there were statistically significant differences in different years (all P<0.05). The detection rate of carbapenem-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa showed an increasing trend, and there were statistically significant differences in different years (all P<0.05).@*Conclusions@#The primary G-bacteria for respiratory infections is Haemophilus influenzae, G-bacilli especially, the mixed infection of G-bacilli, is more likely to cause severe and critical respiratory infections.The resistance rate of G-bacteria infection in children′s respiratory tract to commonly used antibiotics is generally on the rise.

Source analysis of lymphocytes secreting interleukin-22 from spleen of mice infected with Trichinella spiralis at the early encapsulated stage / 中华地方病学杂志

Objective To investigate the cell origin of interleukin (IL)-22-secreting cell of mice infected with Trichinella spiralis (T.spiralis) at the early encapsulated stage.Methods Twelve Balb/c mice were divided into the infected group and the control group according to body weight by random number table.The infected mice were intragastrically administrated with 300 muscle larvae of T.spiralis,and the control mice were given the same amount of normal saline.The IL-22-secreting cell subsets in mouse splenic lymphocytes were detected by flow cytometry at the fourth week after infection.Results The proportion of IL-22-secreting cells in splenic lymphocytes of T.spiralis infected mice was increased when compared with control group [(0.88 ± 0.25)％ vs (0.28 ±0.17)％,t =-4.899,P ＜ 0.05].There was no significant difference between the proportion of CD3+IL-22+ cells and CD3-IL-22+ cells in the splenic lymphocytes of the infected group [(0.29 ± 0.17)％ vs (0.51 ± 0.17)％,t =-2.195,P ＞ 0.05],and the percentage of CD3-IL-22+ cells were similar between the infected group and the control group [(0.51 ± 0.17)％ vs (0.44 ± 0.22)％,t =-0.600,P ＞ 0.05].The proportion of CD3+IL-22+ cells in the infected group was significantly higher than that in the control group [(0.29 ± 0.17)％ vs (0.07 ± 0.06)％,t =-3.068,P ＜ 0.05],and the percentage of CD4+IL-22+ T cells and γδTCR+IL-22+ T cells were obviously increased in CD3+ lymphocytes [(1.28 ± 0.54)％ vs (0.16 ± 0.07)％,(0.33 ± 0.22)％ vs (0.02 ± 0.00)％,t =-4.997,-3.342,P ＜ 0.05].Conclusions The proportion of IL-22-secreting splenic lymphocytes is increased in mice infected with T.spiralis at the early encapsulated stage.The rise is caused by increased numbers of IL-22-secreting CD3 + lymphocytes,especially CD4+ T cells and γδT cells.

Analysis of infection composition and drug resistance to Gram-negative bacilli in children's respiratory tract in Suzhou from 2007 to 2016 / 中华实用儿科临床杂志

Objective To analyze the infection composition and drug resistance to Gram-negative (G-) bacilli in children's respiratory tract in Suzhou,in order to provide evidence for rational use of antibiotics clinically.Methods G-bacilli culture samples were collected from 21 561 cases of nasopharyngeal secretions from patients with respiratory tract infection admitted at the Department of Respiratory,Children's Hospital of Soochow University from January 2007 to December 2016,including 21 246 cases in general wards,and 315 patients who were transferred to the respiratory department after treatment in the Intensive Care Unit(ICU),and the children were divided into the general ward group and the ICU group,and the pathogens were compared and the changes in bacterial susceptibility were dynamically observed between the 2 groups.Results The primary G-bacteria for respiratory infection was Haemophilus influenzae,followed by Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa and Acinetobacter baumannii.The detection rates of Klebsiella pneumoniae and Pseudomonas aeruginosa in the ICU group were 16.8％ (21/125 strains) and 14.4％ (18/125 strains),respectively,which were significantly higher than those in the general ward group [10.0％ (208/2 071 strains),9.2％ (190/2 071 strains)].The detection rates of G-bacteria in the ICU group were 33.7％ (106/315 cases),which were significantly higher than those in the general ward group [9.4％ (1 997/21 246 cases)],and the difference was statistically significant (x2 =210.325,P ＜ 0.001).The rare G-bacillus such as Stenotrophomonas maltophilia,Acinetobacter junii and Burkholderia onion were higher in the ICU group [17.6％ (22/125 strains)] than that in the general ward group [6.4％ (132/2 071 strains)].The rate that of G bacteria with two or more mixed infection in ICU group [17.0％ (18/106 cases)] was significantly higher than in the general ward group [3.4％ (68/1 997 cases)],and the difference was statistically sigmficant(x2 =47.3,P ＜0.05).For the mixed infection,the ICU group was mainly composed of Klebsiella pneumoniae mixed with Pseudomonas aeruginosa or Escherichia coli,while the general ward group was composed of Haemophilus influenzae mixed with Pseudomonas aeruginosa or Escherichia coli.The sensitivity of Haemophilus infiuenzae to Ampicillin,Sultamicillin,Cefuroxime,Cefaclor and Azithromycin decreased,and the sensitivity to Chloramphenicol,Tetracycline and Trimethoprim + Sulfamethoxazole increased year by year,and there were statistically significant differences in different years (all P ＜ 0.05).The sensitivity to Escherichia coli to Ceftazidime decreased year by year,and the sensitivity to Ampicillin and Levofloxacin increased year by year,and there were statistically significant differences in different years (all P ＜ 0.05).The sensitivity to Klebsiella pneumoniae to Cefoperazone/Sulbactam and imipenem decreased,and the sensitivity to Ciprofloxacin and Levofloxacin increased,and there were statistically significant differences in different years (all P ＜ 0.05).The sensitivity to Pseudomonas aeruginosa,Cefoperazone/Sulbactam and Ceftriaxone decreased year by year,and the sensitivity to Levofloxacin increased,and there were statistically significant differences in different years (all P ＜ 0.05).The detection rate of carbapenem-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa showed an increasing trend,and there were statistically significant differences in different years (all P ＜ 0.05).Conclusions The primary G-bacteria for respiratory infections is Haemophilus influenzae,G-bacilli especially,the mixed infection of G-bacilli,is more likely to cause severe and critical respiratory infections.The resistance rate of G-bacteria infection in children's respiratory tract to commonly used antibiotics is generally on the rise.

CXC chemokine receptor 4 regulates breast cancer cell cycle through S phase kinase associated protein 2 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of CXC chemokine receptor 4 (CXCR4) on cell cycle of breast cancer and its molecular mechanisms.</p><p><b>METHODS</b>The expression of CXCR4 and S phase kinase associated protein 2 (Skp2) was detected by real-time fluorescence quantitative PCR (fqRT-PCR) and Western blot in breast cancer cells. The expression of signal proteins and the downstream genes of Skp2 was detected by Western blot. The effect of CXCR4, PI3K/Akt pathway inhibitor LY294002 and ERK pathway inhibitor U0126 on cell cycle of breast cancer was detected by propidium iodide staining.</p><p><b>RESULTS</b>Skp2 was significantly down-regulated in CXCR4-downregulated cells and up-regulated in CXCR4-upregulated cells. CXCR4 also regulated the expression of Skp2 and other downstream genes by signaling protein. The proportion of cells in G/Gphase increased and that in S phase declined in CXCR4-downregulated cell, and the effect was more significant when combined with the use of LY294002 or U0126.</p><p><b>CONCLUSIONS</b>CXCR4 can affect cell cycle and inhibit the proliferation of breast cancer cells by regulating Skp2 gene expression through PI3K/Akt and ERK signaling pathway.</p>

Effects of lncRNA RP11-770J1.3 and TMEM25 expression on paclitaxel resistance in human breast cancer cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of long non-coding RNA(lncRNA) RP11-770J1.3 and transmembrane protein 25 (TMEM25) on paclitaxel resistance in human breast cancer MCF-7/PR cell line.</p><p><b>METHODS</b>The expression of lncRNA RP11-770J1.3 and TMEM25 in human breast cancer MCF-7(paclitaxel sensitive) and MCF-7/PR(paclitaxel resistant) cells were detected by quantitative RT-PCR. The synthetic interfering fragments of lncRNA RP11-770J1.3 and TMEM25 were transfected into MCF-7/PR cells. Sulforhodamine B assay was used to detect the sensitivity of MCF-7/PR cells to paclitaxel after interference of lncRNA RP11-770J1.3 and TMEM25. The expression of multidrug-resistance genes and proteins were detected by qRT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>lncRNA RP11-770J1.3 and TMEM25 were highly expressed in MCF-7/PR cells, and were significantly down-regulated after transfection of synthetic interfering fragments. Down-regulation of lncRNA RP11-770J1.3 and TMEM25 enhanced the sensitivity of MCF-7/PR cells to paclitaxel, and inhibited the expression of MRP, BCRP and MDR1/P-gp (all<0.05). Such effects were more significant when lncRNA RP11-770J1.3 and TMEM25 were both down-regulated (all<0.05).</p><p><b>CONCLUSIONS</b>lncRNA RP11-770J1.3 and TMEM25 are highly expressed in MCF-7/PR cells, and the down-regulation of lncRNA RP11-770J1.3 and TMEM25 can enhance paclitaxel sensitivity in MCF-7/PR cells.</p>

Comparison of expression of growth hormone-releasing hormone and its receptor splice variant 1 in different stages of endometriosis

The present study aims to explore the significance of the expression of growth hormone-releasing hormone [GHRH] and its receptor splice variant 1 [GHRHSV1] in endometriosis [EM]. In this research paper 80 EM patients who received treatment between March 2009 and September 2010 were selected, among which 20 were in stages I, II, III and IV respectively. 50 non-EM patients who underwent hysterectomy because of myoma during the same period comprised the control group. GHRH, GHRH-SV1 and their corresponding mRNA expression in eutopic endometrium and endometriotic tissue as well as ectopic endometrium were detected using immunohistochemical streptavidin-peroxidase [SP] and RT-PCR methods. Analysis of Variance [ANOVA] with Tukey Post Hoc test was used for data analysis and p<0.05 was considered significant. GHRH, GHRH-SV1 and their corresponding mRNA were expressed in eutopic endometrium and endometriotic tissue as well as ectopic endometrium. The mean optical density [OD] values of the GHRH and GHRH-SV1 expression in the experimental group were significantly higher than those in the normal group [p<0.05], and the relative intensity [RI] of GHRH mRNA and GHRH-SV1 mRNA expression in the experimental group was also significantly higher [p<0.05]. The mean OD values of the GHRH and GHRHSV1 expression showed significant differences among endometriotic tissue at different stages of EM [p<0.05], and the RI of GHRH and GHRH-SV1 mRNA expression also showed significant differences [p<0.05]. GHRH and GHRH-SV1 expression levels differ significantly at different stages of endometriosis