Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat co...Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.展开更多
AIM: To study a more accurate quantification of hepatic fibrosis which would provide dinically useful information for monitoring the progression of chronic liver disease. METHODS: Using a cDNA microarray containing ...AIM: To study a more accurate quantification of hepatic fibrosis which would provide dinically useful information for monitoring the progression of chronic liver disease. METHODS: Using a cDNA microarray containing over 22000 clones, we analyzed the gene-expression profiles of non-cancerous liver in 74 patients who underwent hepatic resection. We calculated the ratio of azanstained: total area, and determined the morphologic fibrosis index (MFI), as a mean of 9 section-images. We used the MFI as a reference standard to evaluate our method for assessing liver fibrosis. RESULTS: We identified 39 genes that collectively showed a good correlation (r 〉 0.50) between geneexpression and the severity of liver fibrosis. Many of the identified genes were involved in immune responses and cell signaling. To quantify the extent of liver fibrosis, we developed a new genetic fibrosis index (GFI) based on gene-expression profiling of 4 clones using a linear support vector regression analysis. This technique, based on a supervised learning analysis, correctly quantified the various degrees of fibrosis in both 74 training samples (r = 0.76, 2.2% vs 2.8%, P 〈 0.0001) and 12 independent additional test samples (r = 0.75, 9.8% vs 8.6%, P 〈 0.005). It was far better in assessing liver fibrosis than blood markers such as prothrombin time (r = -0.53), type IV collagen 7s (r = 0.48), hyaluronic acid (r = 0.41), and aspartate aminotransferase to platelets ratio index (APRI) (r = 0.38). CONCLUSION: Our cDNA microarray-based strategy may help clinicians to precisely and objectively monitor the severity of liver fibrosis.展开更多
The polymorphisms of variable number of tandem repeats (VNTR) 3’to the apolipoprotein B (apo B) gene were investigated using polymerase chain reaction (PCR) in a sample of 103 patients with documented coronary heart ...The polymorphisms of variable number of tandem repeats (VNTR) 3’to the apolipoprotein B (apo B) gene were investigated using polymerase chain reaction (PCR) in a sample of 103 patients with documented coronary heart disease (CHD) and 100 healthy individuals selected from Chinese Han nationality.Twelve segregating alleles (3’β29 -51) were observed in the pooled total of 203 subjects. The most common allele was 3’β 37. followed by 3’β39 with frequencies of 0. 362 and 0. 296, respectively. This model of allele distribution was coincident with the results form different ethnic groups, but the relative frequencies of alleles were different. In comparison with the allele frequencies between the patients and controls,alleles bigger than 3’β39 (3’VNTR-B) were significantly more common among the patients than among the controls (P<0. 001). Moreover. in the CHD group patients with plasma levels of TC≥3.88 mmol/L,LDL-C≥2. 59 mmol/L and HDL-C<l. 16mmol/L had significantly higher frequencies of 3’ VNTR-B allele (P<0. 01). Therefore,it is suggested that 3’ VNTR-B allele might be involved in the development of coronary atherosclerosis, presumably through their influences on lipid metabolism.This study supported by “8. 5” grant from Ministry of PublicHealth.展开更多
In order to analyze the nucleoprotein (NP) gene of Crimean-Congo hemorrhagic fever virus (CCHFV), viral RNA was amplified by RT-PCR by using the proof-reading DNA polymerase to produce the complete NP gene. The PCR pr...In order to analyze the nucleoprotein (NP) gene of Crimean-Congo hemorrhagic fever virus (CCHFV), viral RNA was amplified by RT-PCR by using the proof-reading DNA polymerase to produce the complete NP gene. The PCR product was sequenced, analyzed for phylogenesis and cloned into the expression vector pET32a and the recombinant plasmid expressed in E.coli BL-21 with high yield. The primarily purified fused protein was used to coat ELISA plates for the detect antibodies. It was found the similarities between NP gene of BA88166 and other XHFVs in nucleotide level and amino acid contents were very significant, and the NP gene of BA88166 encoded a nucleoprotein with 482 amino acid and a deduced molecular weight (MW) of 54?kDa. Western blot assay showed that the fusion protein expressed in bacteria possessed good antigenicity. The results with ELISA for the detection of the human and animal sera collected in endemic areas were found to be in good accordance to the clinical diagnosis. It concluded that the relations of NP genes of XHFV BA88166 and other XHFVs appeared to be evolutionally close. The methodologies established in this study were accurate, specific, rapid and reproducible for the clinical examinations and epidemiological survey.展开更多
AIM:To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy(EGD) over the past decade.METHODS:EGDs with the indication of dysphagia at an urban,universi...AIM:To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy(EGD) over the past decade.METHODS:EGDs with the indication of dysphagia at an urban,university medical center in 1999,2004 and 2009 were retrospectively identified from the electronic medical record.The entire patient chart,including EGD,pathology,manometry,radiographic and clinician reports,was reviewed for demographic and clinical data and to determine the etiology of dysphagia.The number of EGDs in which an esophageal biopsy was performed was also noted.Gastroesophageal reflux disease(GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition(PPI).Cases of eosinophilic esophagitis(EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field.PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008.Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999,2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect.RESULTS:A total of 1371 cases(mean age 54 years,43% male) met pre-specified inclusion criteria with 191,504 and 675 cases in 1999,2004 and 2009,respectively.Patients were older in 2004 compared to 2009(mean ± SD,54.0 ± 15.7 years vs 52.3 ± 16.8 years,P = 0.02) and there were more males in 1999 compared to 2004(57.5% vs 40.8%,P = 0.005).Overall,GERD(27.6%) and EoE(7.7%) were the most common identifiable causes of dysphagia.An unspecified diagnosis accounted for 21% of overall cases.There were no significant differences in the relative prevalence of achalasia or other motility disorders,peptic stricture,Schatzki's ring,esophageal cancer or unspecified diagnoses over the 10-year time period.There was,however,a decrease in the relative prevalence of GERD(39.3% vs 24.1%,P < 0.001) and increases in the relative prevalence of EoE(1.6% vs 11.2%,P < 0.001) and oropharyngeal disorders(1.6% vs 4.2%,P = 0.02) from 1999 to 2009.Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009(5.4% vs 11.6%,P < 0.001),but not between 1999 and 2004(1.6% P 5.4%,P = 0.21).On the other hand,the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004(39.3% vs 27.7%,P = 0.006),but not between 2004 and 2009(27.7% vs 24.1%,P = 0.36).There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009(36.7% vs 68.7%,P < 0.001) as well as between 2004 and 2009(37.5% vs 68.7%,P < 0.001).While total EGD volume did increase over the 10-year time period,the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE.CONCLUSION:EoE has emerged as a dominant cause of dysphagia in adults.Whether this was due to a rise in disease incidence or increased recognition is unclear.展开更多
基金Supported by The Swiss National Science Foundation, No. 32003B-134963/1"Sir Jules Thorn Trust Reg" Foundation+4 种基金Gustave and Simone Prévot Foundation to Montecucco FEU FP7 AtheroRemo, No. 201668Swiss National Science Foundation, No. 310030B-133127Novartis FoundationSwiss Heart Foundation to Mach F
文摘Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.
基金Supported partly by Grants-in-Aid for Scientific Research (S) (17109013) and for Scientific Research (C) (17591411 and 15591411)a Health and Labor Sciences Research Grant on Hepatitis and BSE (14230801)the Uehara Memorial Foundation, Yasuda Medical Research Foundation, Japanese Foundation for Multidisciplinary Treatment of Cancer, and Princes Takamatsu Cancer research Fund
文摘AIM: To study a more accurate quantification of hepatic fibrosis which would provide dinically useful information for monitoring the progression of chronic liver disease. METHODS: Using a cDNA microarray containing over 22000 clones, we analyzed the gene-expression profiles of non-cancerous liver in 74 patients who underwent hepatic resection. We calculated the ratio of azanstained: total area, and determined the morphologic fibrosis index (MFI), as a mean of 9 section-images. We used the MFI as a reference standard to evaluate our method for assessing liver fibrosis. RESULTS: We identified 39 genes that collectively showed a good correlation (r 〉 0.50) between geneexpression and the severity of liver fibrosis. Many of the identified genes were involved in immune responses and cell signaling. To quantify the extent of liver fibrosis, we developed a new genetic fibrosis index (GFI) based on gene-expression profiling of 4 clones using a linear support vector regression analysis. This technique, based on a supervised learning analysis, correctly quantified the various degrees of fibrosis in both 74 training samples (r = 0.76, 2.2% vs 2.8%, P 〈 0.0001) and 12 independent additional test samples (r = 0.75, 9.8% vs 8.6%, P 〈 0.005). It was far better in assessing liver fibrosis than blood markers such as prothrombin time (r = -0.53), type IV collagen 7s (r = 0.48), hyaluronic acid (r = 0.41), and aspartate aminotransferase to platelets ratio index (APRI) (r = 0.38). CONCLUSION: Our cDNA microarray-based strategy may help clinicians to precisely and objectively monitor the severity of liver fibrosis.
文摘The polymorphisms of variable number of tandem repeats (VNTR) 3’to the apolipoprotein B (apo B) gene were investigated using polymerase chain reaction (PCR) in a sample of 103 patients with documented coronary heart disease (CHD) and 100 healthy individuals selected from Chinese Han nationality.Twelve segregating alleles (3’β29 -51) were observed in the pooled total of 203 subjects. The most common allele was 3’β 37. followed by 3’β39 with frequencies of 0. 362 and 0. 296, respectively. This model of allele distribution was coincident with the results form different ethnic groups, but the relative frequencies of alleles were different. In comparison with the allele frequencies between the patients and controls,alleles bigger than 3’β39 (3’VNTR-B) were significantly more common among the patients than among the controls (P<0. 001). Moreover. in the CHD group patients with plasma levels of TC≥3.88 mmol/L,LDL-C≥2. 59 mmol/L and HDL-C<l. 16mmol/L had significantly higher frequencies of 3’ VNTR-B allele (P<0. 01). Therefore,it is suggested that 3’ VNTR-B allele might be involved in the development of coronary atherosclerosis, presumably through their influences on lipid metabolism.This study supported by “8. 5” grant from Ministry of PublicHealth.
文摘In order to analyze the nucleoprotein (NP) gene of Crimean-Congo hemorrhagic fever virus (CCHFV), viral RNA was amplified by RT-PCR by using the proof-reading DNA polymerase to produce the complete NP gene. The PCR product was sequenced, analyzed for phylogenesis and cloned into the expression vector pET32a and the recombinant plasmid expressed in E.coli BL-21 with high yield. The primarily purified fused protein was used to coat ELISA plates for the detect antibodies. It was found the similarities between NP gene of BA88166 and other XHFVs in nucleotide level and amino acid contents were very significant, and the NP gene of BA88166 encoded a nucleoprotein with 482 amino acid and a deduced molecular weight (MW) of 54?kDa. Western blot assay showed that the fusion protein expressed in bacteria possessed good antigenicity. The results with ELISA for the detection of the human and animal sera collected in endemic areas were found to be in good accordance to the clinical diagnosis. It concluded that the relations of NP genes of XHFV BA88166 and other XHFVs appeared to be evolutionally close. The methodologies established in this study were accurate, specific, rapid and reproducible for the clinical examinations and epidemiological survey.
文摘AIM:To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy(EGD) over the past decade.METHODS:EGDs with the indication of dysphagia at an urban,university medical center in 1999,2004 and 2009 were retrospectively identified from the electronic medical record.The entire patient chart,including EGD,pathology,manometry,radiographic and clinician reports,was reviewed for demographic and clinical data and to determine the etiology of dysphagia.The number of EGDs in which an esophageal biopsy was performed was also noted.Gastroesophageal reflux disease(GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition(PPI).Cases of eosinophilic esophagitis(EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field.PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008.Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999,2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect.RESULTS:A total of 1371 cases(mean age 54 years,43% male) met pre-specified inclusion criteria with 191,504 and 675 cases in 1999,2004 and 2009,respectively.Patients were older in 2004 compared to 2009(mean ± SD,54.0 ± 15.7 years vs 52.3 ± 16.8 years,P = 0.02) and there were more males in 1999 compared to 2004(57.5% vs 40.8%,P = 0.005).Overall,GERD(27.6%) and EoE(7.7%) were the most common identifiable causes of dysphagia.An unspecified diagnosis accounted for 21% of overall cases.There were no significant differences in the relative prevalence of achalasia or other motility disorders,peptic stricture,Schatzki's ring,esophageal cancer or unspecified diagnoses over the 10-year time period.There was,however,a decrease in the relative prevalence of GERD(39.3% vs 24.1%,P < 0.001) and increases in the relative prevalence of EoE(1.6% vs 11.2%,P < 0.001) and oropharyngeal disorders(1.6% vs 4.2%,P = 0.02) from 1999 to 2009.Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009(5.4% vs 11.6%,P < 0.001),but not between 1999 and 2004(1.6% P 5.4%,P = 0.21).On the other hand,the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004(39.3% vs 27.7%,P = 0.006),but not between 2004 and 2009(27.7% vs 24.1%,P = 0.36).There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009(36.7% vs 68.7%,P < 0.001) as well as between 2004 and 2009(37.5% vs 68.7%,P < 0.001).While total EGD volume did increase over the 10-year time period,the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE.CONCLUSION:EoE has emerged as a dominant cause of dysphagia in adults.Whether this was due to a rise in disease incidence or increased recognition is unclear.