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Objective To evaluate the advantages of confocal laser endomicroscopy(CLE)for function repairing of ulcerative colitis(UC). Methods Thirty patients with UC who were diagnosed and treated in the First Affiliated Hospital of Zhejiang University Medical College between July 2014 and December 2016 were enrolled in the study group. The control group consisted of 10 patients who were diagnosed as having colonic polyps with colonoscopy and underwent polypectomy in the same period. Both groups were examined with white light endoscopy and CLE,then the fluorescein leakage score was compared. Results There were 10 out of 30 cases in the study group whose whole intestinal mucosa were judged as normal under white light endoscopy. In the other 20 cases,there were parts of intestinal mucosa being judged as abnormal. All of the 10 cases in the control group were with normal colon mucosa. There was a significant difference on fluorescein leakage score by CLE between the study group which showed normal by white light endoscopy and the control group(P<0.05). The fluorescein leakage score by CLE was significant difference between the abnormal intestinal segment and normal intestinal segment in 20 patients with active UC(P<0.05). Spearman correlation analysis showed that there was non-ranked correlation between the fluorescein leakage score of CLE and histopathological findings of biopsy in UC patients with normal mucosa of the left colon under white light endoscopy(rs=0.394,P>0.05). Conclusion In the process of mucosal healing of UC patients,structural repair can be found firstly through CLE. Mucosal healing under white light endoscopy cannot represent the functional recovery. CLE is more effective than the histopathology in the evaluation of mucosal barrier function.
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Objective To set up a computer-assisted polyp detection system under colonoscopy,and to preliminarily verify its effectiveness.Methods Based on Faster R-CNN algorithm and the open source implementation of the open source framework tensorflow and Faster R-CNN,a computer-assisted polyp detection system under colonoscopy was constructed.According to the size and difficulty of the training set,five test groups were set up:test group one,two,three and four contained 1 000,2 000,4 000 and 6 000 training samples,respectively.Test group five increased the probability of selecting the difficult samples based on 6 000 training samples.In different training sets,the sensitivity,specificity,other classification evaluation parameters,and the evaluation parameters of target detection such as recall and precision of this polyps detection system were calculated.Results Classification evaluation parameters showed that the sensitivities of test group one,two,three,four and five were 90.1%,93.3%,93.3%,93.3 % and 93.5 %,respectively,and the difference was statistically significant (x2 =25.324,P<0.01).The sensitivities of test group two,three,four and five were all higher than that of test group one,and the differences were statistically significant (x2 =13.964,13.508,13.508 and 13.386,all P< 0.006 25).There were no significant differences in specificity and positive predictive value among test groups (both P>0.05).The negative predictive values of test group one,two,three,four and five were 90.4%,93.3%,93.3%,93.3% and 93.5%,respectively,and the differences were statistically significant (x2 =21.862,P<0.01).The negative predictive values of test group two,three,four and five were higher than that of test group one,and the differences were statistically significant (x2=11.447,11.564,11.755,13.760;all P<0.006 25).As the training sample size increased from 1 000 to 2 000,the area under curve (AUC) increased by 2%,and further increased the sample size to 6 000,AUC increased by less than 1 %.At this point maintaining the same sample size while increasing the proportion of difficult samples,AUC increased by 0.4%.The results of evaluation parameters of target detection showed that the recall rate of each test group was 73.6%,79.8%,79.5%,79.8% and 83.3%,respectively,and the differences were statistically significant (x2 =71.936,P<0.01).Among them,the recall rates of test group two,three and four were higher than that of test group one,and the differences were statistically significant (x2 =25.960,23.492 and 25.960,all P<0.006 25),and the recall rate of test group five was higher than those of test group one,two,three and four,and the differences were statistically significant (x2=67.361,9.899,11.527 and 9.899;all P<0.006 25).In addition,the precision rates of test group one,two,three,four and five were 87.9%,85.3%,90.2%,91.4% and 89.2%,respectively,and the difference was statistically significant (x2=48.194,P<0.01).The precision rates of test group three and five were higher than that of test group two,and the differences were statistically significant (x2 =24.508 and 15.223,both P<0.006 25),and the precision rate of test group four was higher than those of test group one and two,and the differences were statistically significant (x2=13.524 and 39.120,both P<0.006 25).As samples size and training difficulty increased,the values of F1-score and mean average precision increased steadily.Conclusions This study initially constructed a computer-assisted polyp detection system under colonoscopy.Currently the maximum sensitivity reached 93.5%,and the maximum recall rate reached 83.3%.Increasing the training set size may improve the polyp detection result to a certain degree,however it will reach a bottleneck.At this time,increasing the training difficulty can further improve the detection scores,especially the recall rate.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in clinical practice, and the spectrum of NAFLD includes nonalcoholic simple fatty liver, nonalcoholic steatohepatitis, and liver cirrhosis. Some patients may even progress to hepatocellular carcinoma. At present, the gold standard for the diagnosis of NAFLD is liver biopsy, but since this is an invasive examination and has high costs, its application is limited in clinical practice. More and more studies have focused on noninvasive diagnostic methods for NAFLD, including serological markers, fatty liver predictive model, and imaging examinations. Emerging diagnostic techniques, including genomics, proteomics, glycomics, and metabolomics, also play an important role in the diagnosis of NAFLD.
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Objective To explore the clinical characteristics and diagnosis of autoimmune pancreatitis(AIP) with the aim to raise awareness of AIP.Methods Clinical data of 32 patients with AIP were retrospectively analyzed,including clinical manifestations,imaging features,laboratory examination,histopathology and treatment from November 2009 to April 2013 in the First Affiliated Hospital of Medical School,Zhejiang University.Results All 32 AIP patients including 25 males and 7 females had a median age of (62.5 ± 12.6) years (27-84 years).The initial symptoms included obstructive jaundice in 50.0%patients (16/32),abdominal pain in 43.8% (14/32),fatigue and weight loss in 12.5% (4/32),and bloody stool in 6.3% (2/32).Laboratory findings revealed abnormal liver function in 6.3% (2/32)patients,increased immunoglobulins in 71.9% (23/32)patients and elevated IgG4 in 8/10 patients.Computerized tomography(CT) scan and ultrasonography were performed in all patients.Diffusely enlarged pancreas were found in 62.5% (20/32) patients and focally enlarged in 37.5% (12/32),additionally main pancreatic duct stenosis in 62.5% (20/32) patients.Nineteen patients obtained histopathological examination,indicating pancreatic interstitial fibrosis,and infiltration of lymphocytes and plasma cells.Conclusions Autoimmune pancreatitis is an autoimmune disease which may be misdiagnosed as pancreatic cancer.The clinical features,laboratory findings,imaging characteristics,and typical histopathologic presentation,as well as good response to glucocorticoids provide supportive evidence for the diagnosis of AIP.
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Objective To explore the role of caveolin-1 in nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet.Methods A total of 12 ten-week-old male C57BL/6 mice were fed with high-fat and high-cholesterol diet for 14 weeks to establish the NAFLD animal model.And six syngeneic mice fed with normal diet at the same time were taken as control.All the mice were sacrificed by the end of 14th week,body weight,liver weight and the changes of serum lipids of the two groups were compared.The changes of caveolin-1 at mRNA and protein levels in the liver of mice with NAFLD were detected by quantitative polymerase chain reaction (qPCR) and Western blot.The liver steatosis of the mice was observed under light microscopy after stained by hematoxylin and eosin.The changes of distribution of caveolin-1 in liver were examined by immunohistochemistry.The differences of caveolin-1 at mRNA and protein level in livers between the two groups were compared by t test.The differences of immunohistochemical scores of caveolin-1 expression in the livers of mice with different degree of fatty liver were analyzed by ordinal variables of two independent samples ranksum test analysis.Results After 14 weeks high-fat and high-cholesterol diet,all the mice of experiment group developed NAFLD.Nine of which were severe and three were moderate.Compared with the control group,serum total cholesterol,high density lipoprotein cholesterol and low density lipoprotein cholesterol of experiment group significantly increased ((1.940 ± 0.300) mmol/L vs (3.771±0.800) mmol/L,(1.120±0.066) mmol/L vs (2.224±0.420) mmol/L,(0.510±0.191) mmol/L vs (1.241±0.660) mmol/L,t=-3.760,-5.474,-3.332,all P<0.01),however there was no significant difference in triglyceride (P>0.05).The caveolin-1 of experiment group significantly increased at mRNA (1.536 ±0.226 vs 0.980± 0.272,t=3.371,P<0.05) and protein levels (0.643±0.240 vs 0.100±0.130,t=4.847,P<0.01).The immunohistochemical results indicated that the increased caveolin-1 expression mainly distributed in the membrane of hepatocytes,cytoplasm and membrane of lipid droplets.Conclusion The up-regulated caveolin-1 expression in the livers of NAFLD mice induced by high-fat and high-cholesterol may be involved in the mechanism of NAFLD.
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OBJECT: To observe the inhibitory effect of Hypoxia inducible factor-1 antisense oligonuclecotide on growth of human hepatocellular carcinoma cells and gene expression of HIF-1, in order to seek a new gene therapy for hepatocellular carcinoma. METHODS: Six Hypoxia inducible factor-1 antisense oligonuclecotides with various concentrations (0.2 micromol/l, 0.4 micromol/l, and 0.8 micromol/l) were transformed into HepG2 cells by lipofectamine reagent. 72 h after transfection, MTS assay was used to detect cellular proliferation. In addition, Hypoxia inducible factor-1 antisense oligonuclecotide2 with various concentrations (0.2, 0.4, 0.8, and 1.0 micromol/l) were transformed into HepG2 cells. About 48 h after transfection, reverse transcription-polymerase chain reaction assay and Western Blot assay were employed to detect the expression of Hypoxia inducible factor-1 gene and the synthesis of Hypoxia inducible factor-1 protein respectively. RESULTS: HepG2 cell growth was inhibited by 6 Hypoxia inducible factor-1 antisense oligonuclecotides at various concentrations. Among them, Hypoxia inducible factor-1 antisense oligonuclecotide2 showed the most effective inhibition ability (P < 0.01), the inhibitory rate was 89.66% at the concentration of 1.0 micromol/l. About 48 h after transfection, Hypoxia inducible factor-1 mRNA expression was downregulated and Hypoxia inducible factor-1 protein synthesis was decreased by antisense oligonuclecotide2. CONCLUSIONS: The hepatocellular carcinoma cell proliferation was inhibited by Hypoxia inducible factor-1 antisense oligonuclecotide. Moreover, the gene expression and protein synthesis of Hypoxia inducible factor-1 were reduced by Hypoxia inducible factor-1 antisense oligonuclecotide. The findings suggested that antisense technique targeting Hypoxia inducible factor-1 might be an effective gene therapy of human hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular/pathology , Hypoxia-Inducible Factor 1/antagonists & inhibitors , Liver Neoplasms/pathology , Oligonucleotides, Antisense/pharmacology , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Hypoxia-Inducible Factor 1/analysis , Hypoxia-Inducible Factor 1/genetics , Liver Neoplasms/therapy , RNA, Messenger/analysisABSTRACT
Objective To compare and analyze gene expression patterns in rat model of nonalcoholic fatty liver disease (NAFLD).Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.The histopathologic changes of the liver were observed and gene expression patterns were analyzed and compared by cDNA mieroarray.Results Hepatocellular steatosis and inflammatory infiltration were observed in model group after high-fat diet for 4 weeks.Fifty-one differential genes were found in model group,20 of which were up-regulated (sterol regulatory element binding factor 1,stearoyl-coenzyme A desaturase 1 and Bcl 2 modifying factor)and 31 were down-regulated (peroxisomal enoyl coenzyme A hydratase 1,heat shock 70 protein 1A and ATPase inhibitory factor 1). The up-regulating genes were involved in lipogenesis and cell apoptosis,while down-regulated genes were involved in fatty acid oxidation, protein modification and energy metabolism.Conclusions The differential expression of genes may involve in the pathogenesis of NAFLD.
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<p><b>OBJECTIVE</b>To explore the relationship between genetic polymorphisms of the ethanol metabolizing enzymes and the occurrence of alcoholic liver disease (ALD).</p><p><b>METHODS</b>Sixty-five healthy male controls and 165 alcoholisms (including 122 ALD patients and 43 male alcohol abusers without liver complications defined as alcohol-dependent) were analyzed by polymerase chain reaction and hybridized with oligonucleotide microarray to detect the polymorphisms of the ethanol metabolizing enzymes genes.</p><p><b>RESULTS</b>The frequencies of alcohol dehydrogenase gene 2 * 1 ( ADH2 * 1 ) allele were shown as 37.69%, 46.51% and 59.02% in control, alcohol-dependent and ALD groups respectively; while those of ADH2 * 2 allele were shown as 62.31 %, 53.49% and 40.98% respectively. No ADH2 * 3 was detected in any of the subjects. The frequency of ADH2 * 1 was significantly higher in alcoholisms (ALD group and alcohol-dependent group) than in healthy controls ( P < 0. 01), and significantly higher in ALD group than in alcohol-dependent group ( P < 0.05) . The frequency of ADH3 * 2 was significantly higher in alcohol-dependents than in healthy controls ( P < 0.05) . The frequencies of ALDH2 * 2 allele mutation were significantly lower in alcoholisms than that in the healthy controls, and the deference between ALD group and alcohol-dependent group was significant. No homozygotes for the mutant ALDH2 * 2 allele were found in either alcoholic groups.</p><p><b>CONCLUSIONS</b>Polymorphic ADH2, ADH3 and ALDH2 genes can affect the propensity for alcohol drinking in Chinese. The alleles of ADH2 * 2, ADH3 * 1 and ALDH2 * 2 are most likely to play a protective role against excessive consumption. ADH2 * 2 and ALDH2 X 2 may contribute to susceptibility for ALD.</p>
Subject(s)
Humans , Male , Alcohol Dehydrogenase , Genetics , Aldehyde Oxidoreductases , Genetics , Genotype , Isoenzymes , Genetics , Liver Diseases, Alcoholic , Genetics , Oligonucleotide Array Sequence Analysis , Polymorphism, GeneticABSTRACT
Objective To investigate the risk factors of death in patients with severe acute pancreatitis within 24 hours after admission. Methods Sixty patients with severe acute pancreatitis admitted from Jan. 2000 to Dec. 2003 were divided into two groups , death group 21 cases and survival group 39 cases. Clinical and laboratory data within 24 hours after admission of those patients were analyzed retrospectively, and Logistic regression analysis was performed. Results The average age in death group was (66.6?16.1)years,breath rate in admission (29?9)/min, urine volume within 24 hours(1062?815) ml,serum creatinine(190.6?120.1) ?mol/L, arterial pressure of O2 (58.5?17.3) mm Hg, APACHE Ⅱ score 19.3?7.5;while correspondent data in survival group were (52.4?13.1) years,(20?2)/min, (1648?575) ml, (94.4?56.0) ?mol/L,(78.8?18.0) mm Hg and 9.1?2.0,respectively. Significant differences were existed between two groups(P
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Objectives Esophageal cancer development and progression is driven by the accumulation of genetic changes. In this study, we used tissue microarray to survey the expression of p53, p16 and COX-2 in esophageal cancer progression and their clinical implication. Methods We tested p53, p16 and COX-2 proteins by immunohistochemistry and tissue microarray in 86 specimens from different stages of esophageal cancer and 40 specimens from adjacent non-cancer tissue. Results The expression of p53 and COX-2 was significantly higher in tumor tissue than that in non-tumor ones. As for the expression of pl6, no significant difference was found between tumor and adjacent tissue. An obvious relation was observed among p53, p16 and COX-2 expression that esophageal carcinogenesis was highly correlated with the positive expression of p53 or COX-2, however, no reciprocal relationship to neoplastic progression was recognized with p53, p16 and COX-2. Conclusion We observed that the tissue with the positive expression of p53 or COX-2 was more likely to develop esophageal cancer. Further work will verify the hypothesis that the expression level of p53 and COX-2 in biopsy specimen is applicable to predict early outset of esophageal cancer.