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miR-93 suppresses proliferation and colony formation of human colon cancer stem cells

World Journal of Gastroenterology 2011年第42期17卷 4711-4717页

作者： xiao-feng yu jian zou zhi-jun bao jie dong Department of Gastroenterology Huadong Hospital Fudan University Shanghai 200040 China

AIM： TO identify differentially expressed microRNAs （miRNAs） in human colon cancer stem cells （SW1116csc） and study their function in SW1116csc proliferation. METHODS： SW1116csc were isolated from the human colon cancer cell line, SW1116 and cultured in serum- free medium. A miRNA microarray was used to detect differential expression profiles of rniRNAs in SW1116csc and SW1116 cells. Real-time quantitative polymerase chain reaction （PCR） was performed to verify the dif- ferential expression of candidate miRNAs obtained from the microarray. Target mRNAs of differentially expressed miRNAs were predicted with target predic- tion tools, miRNA expression plasmids were transfected into SW1116csc using Lipofectamine 2000 reagent. Cell proliferation curves were generated with trypan blue staining, and the colony formation rate of transfected cells was measured with the soft agar colony formation assay. Expression of target mRNAs and proteins from differentially expressed miRNAs were detected using reverse transcription （RT）-PCR and western ***： Compared with expression in SW1116 cells, 35 miRNAs （including hsa-miR-192, hsa-miR-29b, hsa-miR-215, hsa-miR-194, hsa-miR-33a and hsa- miR-32） were upregulated more than 1.5-fold, and 11 miRNAs （including hsa-miR-93, hsa-miR-1231, hsa- miRPlus-F1080, hsa-miR-524-3p, hsa-miR-886-3p and hsa-miR-561） were downregulated in SW1116csc. The miRNA microarray results were further validated with quantitative RT-PCR. miR-93 was downregulated, and its predicted mRNA targets included BAMBI, CCND2, CDKNIA, HDACS, KIF23, MAP3K9, MAP3K11, MYCN, PPARD, TLE4 and ZDHHCl. Overexpressed miR-93 sig- nificantly inhibited cell proliferation and colony forma- tion by SW1116csc. Furthermore, miR-93 negatively regulated the mRNA and protein levels of HDAC8 and TLE4. CONCLUSION： Some miRNAs were differentially ex- pressed during differentiation of SW1116csc into SW1116 cells, miR-93 may inhibit SW1116csc proliferation and colony formation.

关键词： miR-93 Stem cell Colon cancer Expres-sion profile

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Proteome of human colon cancer stem cells:A comparative analysis

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World Journal of Gastroenterology 2011年第10期17卷 1276-1285页

作者： jian zou xiao-feng yu zhi-jun bao jie dong Department of Gastroenterology Huadong Hospital Fudan UniversityShanghai 200040 China

AIM： To isolate and identify the biological characteristics of human colon cancer stem cells （SW1116 cells） and further study their proteome. METHODS： SW1116 cells were isolated and cultured with a serum-free medium （SFM）. Sphere formation was assayed to observe the formation of colon cancer stem cell spheres. SW1116 cells were inoculated into a serum-containing medium for observing their differentiation characteristics. Proliferation curve and cross-resistance of SWl116 cells to different drugs were detected by MTT. Percentage of SP cells in SW1116 cells was detected with Hoechst33342 staining. Telomerase activity in SW1116cells was checked by polymerase chain reaction （PCR）-enzyme linked immunosorbent assay. Expressions of stem cell relevant genes and proteins were detected by reverse transcription-PCR and Western blot, respectively. Total protein was isolated from SW1116 cells by two-dimensional gel electrophoresis （2-DE） and differentially expressed proteins were identified by tandem mass spectrometry （MALDI-TOF/TOF）. RESULTS： The isolated SW1116 cells presented as spheroid and suspension growths in SFM with a strong self-renewal, proliferation, differentiation and drug-resistance ability. The percentage of SP cells in SW1116 cells was 38.9%. The SW1116 cells co-expressed the CD133 and CD29 proteins. The telomerase activity in SW1116 cells was increased. The expressions of different stem cell relevant genes and proteins were detected. The proteomic analysis showed that the 26 protein spots were differently expressed in SW1116 cells and 10 protein spots were identified as ubiquitin fusion- degradation l-like protein, nuclear chloride channel protein, tubulin 13, Raichu404X, stratifin, F-actin cap- ping protein α-1 subunit, eukaryotic translation elongation factor 1 delta isoform 2, hypothetical protein, glyceraldehyde-3-phosphate dehydrogenase and guanine nucleotide binding protein 13 polypeptide 2-like 1, respectively. CONCLUSION： SW1116 cells are biologically c

关键词： Proteome Stem cell Colon cancer Isola-tion Characterization

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Azithromycin-containing versus standard triple therapy for Helicobacter pylori eradication:A meta-analysis

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World Journal of Gastroenterology 2009年第48期15卷 6102-6110页

作者： jie dong xiao-feng yu jian zou Deoartment of Gastroenterology Huadong Hospital Fudan University Shanghai 200040 China

AIM： To evaluate whether adding azithromycin to firstline Helicobacter pylori （H pylorl） eradication improved eradication and reduced side effects. METHODS： Eligible articles were identified by searches of electronic databases. We included all randomized trials that compared azithromycin-containing with standard triple-therapy regimens for first-line treatment of H pylori infection. Statistical analysis was performed with Review Manager 5.0.10. Sub-analyses were also performed. RESULTS： We identified 14 randomized trials （1431 patients）. Pooled Hpylori eradication rates were 72.01% （95% CI： 58.09%-85.93%） and 69.78% （95% CI： 66.47%-73.09%） for patients with or without azithromycin by intention-to-treat analysis, and the odds ratio （OR） was 1.17 （95% CI： 0.64-2.14）. The occurrence of side effects differed significantly and was 15.81% （95% CI： 12.50%-19.12%） and 25.20% （95% CI： 21.44%-28.96%） for treatment with or without azithromycin, respectively, and the summary OR was 0.58 （95% CI： 0.41-0.82）. Furthermore, the azithromycin-containing group had a lower occurrence of diarrhea, nausea and taste disturbance. CONCLUSION： Our review suggests that azithromycincontaining triple-therapy regimens could be equally effective in eradication of Hpylori compared with standard first-line triple-therapy regimens.

关键词： Azithromycin He/icobacter pylori Combination drug therapy Adverse effects

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Coffee drinking and pancreatic cancer risk:A meta-analysis of cohort studies

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World Journal of Gastroenterology 2011年第9期17卷 1204-1210页

作者： jie dong jian zou xiao-feng yu Department of Gastroenterology Huadong Hospital Fudan University Shanghai200040 China

AIM:To quantitatively assess the relationship between coffee consumption and incidence of pancreatic cancer in a meta-analysis of cohort studies. METHODS:We searched MEDLINE,EMBASE,Science Citation Index Expanded and bibliographies of retrieved *** were included if they reported relative risks(RRs)and corresponding 95%CIs of pancreatic cancer with respect to frequency of coffee *** performed random-effects meta-analyses and metaregressions of study-specific incremental estimates to determine the risk of pancreatic cancer associated with a 1 cup/d increment in coffee consumption. RESULTS:Fourteen studies met the inclusion criteria, which included 671 080 individuals(1496 cancer events) with an average follow-up of 14.9 *** with individuals who did not drink or seldom drank coffee per day,the pooled RR of pancreatic cancer was 0.82 (95%CI:0.69-0.95)for regular coffee drinkers,0.86 (0.76-0.96)for low to moderate coffee drinkers,and 0.68(0.51-0.84)for high *** subgroup analyses,we noted that,coffee drinking was associated witha reduced risk of pancreatic cancer in men,while this association was not seen in *** associations were also similar in studies from North America,Europe, and the Asia-Pacific region. CONCLUSION:Findings from this meta-analysis suggest that there is an inverse relationship between coffee drinking and risk of pancreatic cancer.

关键词： Coffee Cohort study Meta-analysis Pancreatic neoplasm

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Fish consumption and risk of gastrointestinal cancers:A meta-analysis of cohort studies

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World Journal of Gastroenterology 2014年第41期20卷 15398-15412页

作者： xiao-feng yu jian zou jie dong Department of Gastroenterology Huadong Hospital Fudan University

AIM: To assess quantitatively the relationship between fish intake and the incidence of gastrointestinal cancers in a meta-analysis of cohort studies.

关键词： Diet Cancer prevention Fish intake Gastrointestinal cancer

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A meta-analysis of the effects of energy intake on risk of digestive cancers

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World Journal of Gastroenterology 2012年第48期18卷 7362-7370页

作者： xiao-feng yu Yi-Qian Wang jian zou jie dong Department of Gastroenterology Huadong HospitalFudan University

AIM:To quantitatively assess the relationship between energy intake and the incidence of digestive cancers in a meta-analysis of cohort ***:We searched MEDLINE,EMBASE,Science Citation Index Expanded,and the bibliographies of retrieved *** were included if they reported relative risks(RRs) and corresponding 95% CIs of digestive cancers with respect to total energy *** RRs were not available in the published article,they were computed from the exposure *** were extracted independently by two investigators and discrepancies were resolved by discussion with a third *** performed fixed-effects meta-analyses and meta-regressions to compute the summary RR for highest versus lowest category of energy intake and for per unit energy intake and digestive cancer incidence by giving each study-specific RR a weight that was proportional to its ***:Nineteen studies consisting of 13 independent cohorts met the inclusion *** studiesincluded 995 577 participants and 5620 incident cases of digestive cancer with an average follow-up of 11.1 years.A significant inverse association was observed between energy intake and the incidence of digestive *** RR of digestive cancers for the highest compared to the lowest caloric intake category was 0.90(95% CI 0.81-0.98,P 0.05) or pancreatic(RR 0.79,95% CI 0.49-1.09,P > 0.05) *** were also similar in studies from North America and *** RR was 1.02(95% CI 0.79-1.25,P > 0.05) when considering the six studies conducted in North America

关键词： Diet Cancer prevention Energy intake Digestive cancer

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Interaction of 14-3-3σ with KCMF1 suppresses the proliferation and colony formation of human colon cancer stem cells

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World Journal of Gastroenterology 2013年第24期19卷 3770-3780页

作者： jian zou Lin Mi xiao-feng yu jie dong Department of Gastroenterology Huadong Hospital Fudan University

AIM: To investigate the biological function of 14-3-3σ protein and to look for proteins that interact with 14-3-3σ protein in colon cancer stem cells. METHODS: Reverse transcription polymerase chain reaction was performed to amplify the 14-3-3σ gene from the mRNA of colon cancer stem cells. The gene was then cloned into the pGEM-T vector. After being sequenced, the target gene 14-3-3σ was cut from the pGEM-T vector and cloned into the pGBKT7 yeast expression plasmid. Then, the bait plasmid pGBKT7-14-3-3σ was transformed into the yeast strain AH109. After the expression of the pGBKT7-14-3-3σ fusion protein in the AH109 yeast strain was accomplished, a yeast two-hybrid screening assay was performed by mating AH109 with Y187 that contained a HeLa cDNA library plasmid. The interaction between the 14-3-3σ protein and the proteins obtained from positive colonies was further confirmed by repeating the yeast two-hybridscreen. After extracting and sequencing the plasmids from the positive colonies, we performed a bioinformatics analysis. A coimmunoprecipitation assay was performed to confirm the interaction between 14-3-3σ and the proteins obtained from the positive colonies. Finally, we constructed 14-3-3σ and potassium channel modulatory factor 1 (KCMF1) siRNA expression plasmids and transfected them into colon cancer stem cells. RESULTS: The bait plasmid pGBKT7-14-3-3σ was constructed successfully, and the 14-3-3σ protein had no toxic or autonomous activation effect on the yeast. Nineteen true-positive colonies were selected and sequenced, and their full-length sequences were obtained. We searched for homologous DNA sequences for these sequences from GenBank. Among the positive colonies, four coding genes with known functions were obtained, including KCMF1 , quinone oxidore-ductase (NQO2 ), hydroxyisobutyrate dehydrogenase (HIBADH ) and 14-3-3σ . For the subsequent coimmu-noprecipitation assay, the plasmids PCDEF-Flag-14-3-3σ, PCDEF-Myc-KCMF1, PCDEF-Myc-NQO2 and PCDEF-Myc

关键词： 14-3-3σ protein Interacting proteins Yeast two-hybrid system Colon cancer stem cells

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XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer:An open-labeled,multicenter,randomized,prospective phase III trial(EXELOX)

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Cancer Communications 2022年第4期42卷 314-326页

作者： xiao-dong Zhu Ming-Zhu Huang yu-Sheng Wang Wan-Jing feng zhi-yu Chen Yi-Fu He xiao-Wei Zhang Xin Liu Chen-Chen Wang Wen Zhang jie-Er Ying jun Wu Lei Yang Yan-Ru Qin jian-feng Luo xiao-Ying Zhao Wen-Hua Li Zhe Zhang Li-Xin Qiu Qi-Rong Geng jian-Ling zou jie-yun Zhang Hong Zheng Xue-feng Song Shu-Sheng Wu Cheng-Yan Zhang Zhe Gong Qin-Qin Liu xiao-feng Wang Qi Xu Qi Wang jian-Mei Ji jian Zhao Wei-jian Guo Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032P.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032P.R.China Department of Gastroenterology Shanxi Cancer HospitalTaiyuanShanxi 030013P.R.China Department of Medical Oncology The First Affiliated HospitalDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230031P.R.China Department of Abdominal Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Cancer and Basic Medicine(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310005P.R.China Department of Medical Oncology The First People’s Hospital of ChangzhouChangzhouJiangsu 213004P.R.China Department of Gastroenterology Nantong Tumor HospitalNantongJiangsu 226006P.R.China Department of Oncology Zhengzhou University First Affiliated HospitalZhengzhouHenan 450052P.R.China Department of Biostatistics School of Public HealthFudan UniversityShanghai 200032P.R.China Department of medical oncology Cancer Hospital of Fudan UniversityMinhang BranchShanghai 200032P.R.China

Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating ***:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor *** primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat ***:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two *** patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX *** rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during ***:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC ***,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

关键词： Advanced gastric cancer chemotherapy XELOX doublet regimen EOX triplet regimen noninferiority quality of life phase III trial

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Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis:a prospective,comparative study

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World Journal of Pediatrics 2021年第6期17卷 643-652页

作者： Jing-Jing Wang dong-jie Wang Hai-dong Fu De-Xuan Wang Qing Yang xiao-jie Peng Rui Fu Huan-Dan Yang Rui-feng Zhang xiao-Wen Wang jiang-Wei Luan Fei Zhao Qiu-Xia Chen Fang-Fang Liang Lu Cao jian-jiang Zhang Ying-jie Li Yang dong Hui-Mei Huang Ying bao xiao-yu Shen Wei Zhou Guang-Hai Cao Cui-Hua Liu Yan-Yan Jin Mei-Lin Ma Li jiang Qian Shen Hong Xu jian-Hua Mao Department of Nephrology TChildren's Hospital of Zhejiang University School of MedicineNational Clinical Research Center of Child HealthHangzhouChina Department of Nephrology The Second Attiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhouChina Department of Nephrology Jiangxi Provincial Children's HospitalNanchangChina Department of Nephrology Xuzhou Children's HospitalXuzhou Medical UniversityXuzhouChina Department of Nephrology Wuhan Children's Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Nephrology Children's Hospital of Nanjing Medical UniversityNanjingChina Department of Rheumatology Shenzhen Children's HospitalShenzhenChina Department of Pediatrics The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina Department of Nephrology Guangzhou Women and Children's Medical CenterGuangzhouChina Department of Nephrology Anhui Provincial Children's HospitalHefeiChina Department of Nephrology The Affiliated Children Hospital of Xi'an Jiaotong UniversityXi'anChina Department of Nephrology Shanghai Children's Medical CenterShanghaiChina Department of Nephrology and Rheumatology Children's Hospital Affiliated to ZhengZhou UniversityHenan Children's HospitalZhengZhou Children's HospitalZhengZhouChina Medical Affairs Department Ferring Pharmaceuticals(Asia)Company LimitedShanghaiChina Marketing Department Ferring Pharmaceuticals(Asia)Company LimitedShanghaiChina Department of Nephrology The Children's Hospital of Fudan UniversityShanghaiChina

Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding *** A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding *** primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two *** secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to *** Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified *** diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS *** addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to *** The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

关键词： Children Compliance Nocturnal enuresis Voiding diary

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Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates

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Virologica Sinica 2022年第6期37卷 804-812页

作者： xiao-Li feng Dandan yu Mi Zhang xiaohong Li Qing-Cui zou Wentai Ma jian-bao Han Ling Xu Cuixian Yang Wang Qu Zhong-Hua Deng junyi Long Yanghaopeng Long Mingkun Li Yong-Gang Yao Xing-Qi dong jianxiong Zeng Ming-Hua Li Kunming National High-level Biosafety Research Center for Non-Human Primates Center for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunming650107China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming650201China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunming650107China Department of Infectious Diseases Yunnan Provincial Infectious Diseases HospitalKunming650301China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciencesand China National Center for BioinformationBeijing100101China University of Chinese Academy of Sciences Beijing100049China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming650201China Kunming College of Life Science University of Chinese Academy of SciencesKunming650204China yunnan Key Laboratory of Biodiversity Information Kunming Institute of ZoologyChinese Academy of SciencesKunming650201China

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally,from B.1.17(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta) to B.1.1.529(Omicron). The emerging or reemerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics,pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2(hACE2)transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

关键词： SARS-CoV-2 Variants of concern(VOC) Alpha Delta hACE2 transgenic mice Hamster

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