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Chemokines and PI3K/AKT signaling pathway mediate the spontaneously ruptured hepatocellular carcinoma through the regulation of the cell cycle
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作者 Yan Zhang Yang-Liu Zhou +4 位作者 Na Xu Tao Meng Zhen-Zhen Wang fa-ming pan Li-Xin Zhu 《Hepatobiliary & Pancreatic Diseases International》 2025年第5期511-526,共16页
Background:The incidence of spontaneously ruptured hepatocellular carcinoma(srHCC)has been shown to significantly elevate mortality rates.However,the precise mechanisms underlying srHCC remain poorly understood.Method... Background:The incidence of spontaneously ruptured hepatocellular carcinoma(srHCC)has been shown to significantly elevate mortality rates.However,the precise mechanisms underlying srHCC remain poorly understood.Methods:Analysis was conducted on the data of 198 hepatocellular carcinoma(HCC)patients to inves-tigate the factors contributing to srHCC.The clinical data of 33 transcriptome HCC patients were served for verification.An in-depth transcriptome analysis was conducted to investigate the distinctions between 26 cases of srHCC and 35 cases of non-ruptured hepatocellular carcinoma(nrHCC).Weighted Gene Co-expression Network Analysis(WGCNA)tool was utilized to develop a gene co-expression network.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathways enrichment,and protein-protein interaction(PPI)network were carried out.The corresponding samples for spontaneously rup-tured hepatocellular carcinoma tissue(srHCC-T)and ruptured hepatocellular carcinoma paracancerous tissue(srHCC-P)were selected for verification.Transcriptional data were validated through reverse tran-scription quantitative polymerase chain reaction(RT-qPCR).Immunofluorescence(IF),immunohistochem-istry(IHC)and Western blot were used to detect the protein expression.Results:Our results showed that white blood cell(WBC)and monocyte levels were significant inde-pendent risk factors for srHCC(P<0.05).There was a strong association between the srHCC-T and the expression of cell cycle-related genes BUB1B and macrophage function-related gene MACRO.Furthermore,chemokines and the PI3K/AKT signaling pathway play a crucial role in regulating the cell cycle process through a complex network of interactions,ultimately impacting the occurrence of srHCC.Conclusions:Our study confirms that chemokines and the PI3K/AKT signaling pathway mediate the occur-rence of HCC rupture by regulating the cell cycle.We provide a theoretical basis for the clinical treatment of srHCC. 展开更多
关键词 Spontaneously ruptured hepatocellular carcinoma Non-ruptured hepatocellular carcinoma TRANSCRIPTOME Cell cycle CHEMOKINES
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TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways
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作者 Yan Zhang Zhen-Zhen Wang +4 位作者 An-Qi Han Ming-Ya Yang Li-Xin Zhu fa-ming pan Yong Wang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第2期195-209,共15页
Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate... Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC. 展开更多
关键词 TuBG1 Hepatocellular carcinoma APOPTOSIS Cell cycling IMMUNOMODULATORS
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Meta-analysis comparison of endoscopic papillary balloon dilatation and endoscopic sphincteropapillotomy 被引量:30
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作者 Hong-Chuan Zhao Liang He +2 位作者 Da-Chen Zhou Xiao-Ping Geng fa-ming pan 《World Journal of Gastroenterology》 SCIE CAS 2013年第24期3883-3891,共9页
AIM: To assess endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincteropapillotomy (EST) for common bile duct (CBD) stone removal using a meta-analysis. METHODS: Randomized controlled trials published ... AIM: To assess endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincteropapillotomy (EST) for common bile duct (CBD) stone removal using a meta-analysis. METHODS: Randomized controlled trials published from 1990 to 2012 comparing EPBD with EST for CBD stone removal were evaluated. This meta-analysis was performed to estimate short-term and long-term com-plications of these two treatments. The fixed random effect model or random effect model was established to analysis the data. Results were obtained by analyz-ing the relative risk, odds ratio, and 95%CI for a given comparison using RevMan 5.1. Statistical significance was defined asP < 0.05. Risk of bias was evaluated us-ing a funnel plot. RESULTS: Of the 1975 patients analyzed, 980 of them were treated with EPBD and 995 were treated with EST. Of the patient population, patients in the EPBDgroup were younger (OR=-1.16, 95%CI:-1.49 to 0.84, P<0.01). There were no significant differences in gender proportion, average size of stones, number of gallstones, previous cholecystectomy, the incidence of duodenal diverticulum, CBD diameter or the total follow-up time between EST and EPBD groups. Com-pared with EST, the total stone clearance in the EPBD group decreased (OR=0.64, 95%CI: 0.42 to 0.96,P=0.03), the use of stone extraction baskets significantly increased (OR=1.91, 95%CI: 1.41 to 2.59, P<0.01), and the incidence of pancreatitis significantly increased (OR=2.79, 95%CI: 1.74 to 4.45, P<0.0001). The incidence of bleeding (OR=0.12, 95%CI: 0.04 to 0.34, P<0.01) and cholecystitis (OR=0.41, 95%CI: 0.20 to 0.84, P=0.02) significantly decreased. The stone re-currence rate also was significantly reduced in EPBD (OR=0.48, 95%CI: 0.26 to 0.90, P=0.02). There were no significant differences between the two groups with the incidence of stone removal at first attempt, hours of operation, total short-term complications and infection, perforation, or acute cholangitis. CONCLUSION: Although the incidence of pancreatitis was higher, the overall stone clearance rate and risk of bleeding was lower with EPBD compared to EST. 展开更多
关键词 Common BILE duct stone ENDOSCOPIC papil-lary BALLOON DILATATION ENDOSCOPIC sphincteropapilloto-my META-ANALYSIS
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Relationship between interleukin-6 polymorphism and susceptibility to chronic hepatitis B virus infection 被引量:1
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作者 Xiao-Miao Zhao Yu-Feng Gao +2 位作者 Qin Zhou fa-ming pan Xu Li 《World Journal of Gastroenterology》 SCIE CAS 2013年第40期6888-6893,共6页
AIM:To identify the relationship between tag single nucleotide polymorphisms(tag SNPs) of interleukin-6(IL-6) gene and susceptibility to chronic hepatitis B virus(HBV) infection in a Han Chinese population.METHODS:We ... AIM:To identify the relationship between tag single nucleotide polymorphisms(tag SNPs) of interleukin-6(IL-6) gene and susceptibility to chronic hepatitis B virus(HBV) infection in a Han Chinese population.METHODS:We performed a case-control study of501 Chinese patients with chronic HBV infection and301 self-limiting HBV-infected individuals as controls.Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract highdensity tubes. Tag SNPs were identified using genotype data from the panel(Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6(rs17147230A/T,rs2066992G/T,rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed.RESULTS:Five haplotypes were involved in the analysis,with frequencies higher than 0.03. One of the haplotypes,TTAA,was significantly different between the two groups. Overall haplotype P values were:ATAA,P = 0.605,OR(95%CI) = 1.056(0.860-1.297); TGAG,P = 0.385,OR(95%CI) = 1.179(0.813-1.709); TGGG,P = 0.549,OR(95%CI) = 1.087(0.827-1.429); TTAA,P = 0.004,OR(95%CI) = 0.655(0.491-0.873); TTAG,P = 0.266,OR(95%CI) = 1.272(0.832-1.944). However,the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were:rs17147230,P = 0.696,OR(95%CI) = 1.041(0.850-1.276); rs2066992,P = 0.460,OR(95%CI)= 1.090(0.868-1.369); rs2069837,P = 0.898,OR(95%CI) = 0.983(0.759-1.274); rs2069852,P = 0.165,OR(95%CI) = 0.859(0.693-1.064). Overall genotype P values were:rs17147230,P = 0.625; rs2066992,P= 0.500; rs2069837,P = 0.853; and rs2069852,P =0.380.CONCLUSION:The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population. 展开更多
关键词 Chronic HEPATITIS B virus infection INTERLEUKIN-6 Single NUCLEOTIDE POLYMORPHISM Genetic SUSCEPTIBILITY HAPLOTYPE
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Single Nucleotide Polymorphisms rs2227284, rs2243283 and rs2243288 in the IL-4 Gene show no Association with Susceptibility to Chronic Hepatitis B in a Chinese Han Population
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作者 Qin Zhou Yu-feng Gao +2 位作者 Xiao-miao Zhao fa-ming pan Xu Li 《国际感染病学(电子版)》 CAS 2014年第1期16-21,共6页
Objective To investigate the relationship between single nucleotide polymorphisms(SNPs) of the interleukin-4(IL-4) gene and outcome of hepatitis B virus(HBV) infection in a Chinese Han population.Methods Total of 501 ... Objective To investigate the relationship between single nucleotide polymorphisms(SNPs) of the interleukin-4(IL-4) gene and outcome of hepatitis B virus(HBV) infection in a Chinese Han population.Methods Total of 501 patients with chronic hepatitis B virus(HBV) infection and 301 controls with selflimiting HBV infection were studied. Three tag SNPs in the IL-4 gene(rs2227284G/T, rs2243283C/G and rs2243288A/G) were genotyped by the Multiplex snapshot technique. The genotype and allele frequencies were calculated and analyzed.Results The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were: rs2227284, P = 0.655, odds ratio(OR) [95% confidence interval(CI)] = 1.070(0.793-1.445); rs2243283, P = 0.849, OR(95% CI) = 0.976(0.758-1.257); rs2243288, P = 0.659, OR(95% CI) = 1.060(0.818-1.375). Overall genotype P values were: rs2227284, P = 0.771; rs2243283, P = 0.571; rs2243288, P = 0.902. There were no statistically significant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs also had no significant differences between the two groups. Conclusions The three tag SNPs of IL-4 were not associated with the outcome of HBV infection in the Han Chinese population. 展开更多
关键词 Hepatitis B virus IL-4 gene POLYMORPHISM
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