Objective: To explore the characteristics of NF-闎 activation in the progress of pancreatitis, the relationship with expression of TNF- in the inflammatory reaction, and prevent the exacerbation of pancreatitis by usi...Objective: To explore the characteristics of NF-闎 activation in the progress of pancreatitis, the relationship with expression of TNF- in the inflammatory reaction, and prevent the exacerbation of pancreatitis by using NAC. Method: Forty-eight rats were divided into three groups: therapy (group C), pancreatitis (group B) and control (group A). NAC served as the inhibitor of NF-闎 activation. In the time intervals of 1.5, 3.0, 6.0, 12.0 hour, NF-闎 activation was detected with flow cytometry (FCM) and the expression of TNF- mRNA and protein with in situ hybridization (ISH) and enzyme-linked immuno-sorbent assay (ELISA) respectively. Meanwhile, the level of lipase and amylase in the serum was assayed and the pathological change was evaluated. Result: NF-闎 activation in the pancreatitis group was higher than that in the control group (P<0.01), peaked at 3 hours, and was depressed by the inhibitor of NF-闎, NAC. The expression of TNF- as well as the level of lipase and amylase in the serum also rose synchronously with activation of NF-闎. In contrast to group A, it was significantly different (P<0.01) in group B. After using NAC in group C, all of these values were decreased and the in-flammatory reaction in the pancreas abated evidently. The pathology changes of the pancreas were shown to be alleviated in group C. Conclusion: First, NF-闎 activity is intensively initiated in the course of pancreatitis and shown to have closely relationship with the release of cytokines. Second, use of NAC markedly depressed NF-闎 activation. TNF- expression is down regulated by cytokines. It is suggested that NAC probably acts as a useful agent for treatment of pancreatitis by indirectly inhibiting activation of NF-闎.展开更多
Hepatitis C virus（HCV）-specific CD8^＋ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the vi...Hepatitis C virus（HCV）-specific CD8^＋ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 （PD-1）. This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8^＋ T cells are exhausted with impairment of several effector mechanisms, such as： type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand （PD-L1）. After this blockade, HCV-specific CD8^＋ T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-l-expressing intrahepatic HCV-specific CD8^＋ T cells do not restore their effector abilities after PD-1/ PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gClq receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response aclainst HCV to succeed in clearing the infection.展开更多
Objective: To investigate whether bacterial DNA involving in the pathogenesis of systemic inflammatory response syndrome (SIRS) and possible mechanism. Methods: Escherichia coli DNA (EC DNA) was extracted from Escheri...Objective: To investigate whether bacterial DNA involving in the pathogenesis of systemic inflammatory response syndrome (SIRS) and possible mechanism. Methods: Escherichia coli DNA (EC DNA) was extracted from Escherichia coli 25922 with alkaline lysis method. The mice mortality was observed after EC DNA was injected into mice via caudal vein. The changes of serum TNF-α and IL-6 levels in rats were measured with ELISA after rats were given EC DNA. Calf thymus DNA and lipopolysaccharide (LPS) were used as the control, respectively. Results: EC DNA led mice to death with notable dose-effect relationship (LD50=11.51 mg/kg), but CT DNA didn't. The peak level of TNF-αwas lower in EC DNA group than in LPS group (P＜0. 05), though the former reaching the peak I h earlier than the latter. However, they had coordinate ability to induce IL-6 release in rats, and no significant difference was seen in serum IL-6 peak level between 2 groups. Conclusion: EC DNA leads mice to death, and induces the increases of serum TNF-αand IL-6 levels in rats. EC DNA has the effect equal to LPS in inducing SIRS by triggering cytokines cascade.展开更多
The differential diagnosis of Behcet's disease(BD) from inflammatory bowel disease(IBD) is sometimes difficult and challenging.Hereby,we suggested the utility of anti-saccharomyces cerevisiae antibody(ASCA) and an...The differential diagnosis of Behcet's disease(BD) from inflammatory bowel disease(IBD) is sometimes difficult and challenging.Hereby,we suggested the utility of anti-saccharomyces cerevisiae antibody(ASCA) and anti-neutrophilic cytoplasmic antibody(p-ANCA) in the differential diagnosis of BD from IBD.展开更多
AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were ad...AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.展开更多
Objective: To build a cell model of LPS-induced hyper- and hypo-responsiveness in macrophage cells . Methods: Macrophage cell line RAW264. 7 was pre-cultured with or without 10 ng/ml LPS for 18 h, then challenged with...Objective: To build a cell model of LPS-induced hyper- and hypo-responsiveness in macrophage cells . Methods: Macrophage cell line RAW264. 7 was pre-cultured with or without 10 ng/ml LPS for 18 h, then challenged with lipopolysaccharide(LPS) , or MDP, Zymosan, PAF, FMLP, PMA for 24 h. The levels of TNF-α , IL-1 , IL-6, IL-10 , NO and O2-, were measured. Results: LI'S pretreatment markedly inhibited TNF-a NO and IL-6 production, but increased IL-1, IL-10 and O2- release to LPS challenge. LPS pretreatment also altered macrophage responsiveness to the other stimuli. Conclusion: LPS can induce hyper- and hypo-responsiveness simultaneously in the macrophage cell lines. Changes in macrophage responsiveness depend on stimuli and effectors which are measured.展开更多
Inflammatory bowel disease （IBD） results from the interaction between an individual＇s immune response and precipitant environmental factors, which generatean anomalous chronic inflammatory response in thosewho are ...Inflammatory bowel disease （IBD） results from the interaction between an individual＇s immune response and precipitant environmental factors, which generatean anomalous chronic inflammatory response in thosewho are genetically predisposed. Various feeding practices have been implicated in the origin of IBD based on epidemiological observations in developed countries, but we do not have solid evidence for the etiological role played by specific food types. IBD is associated with frequent nutritional deficiencies, thepattern and severity of which depends on the extent,duration and activity of the inflammation. Nutritional support allows these deficiencies in calories, macro and micronutrients to be rectified. Enteral nutrition is also aprimary therapy for IBD, especially for Crohn＇s disease,as it allows the inflammatory activity to be controlled,kept in remission, and Drevents or delays the need forsurgery. Nutritional support is especially important in childhood IBD as an alternative to pharmacological treatment. This report discusses the complex relationship between diet and IBD.展开更多
AIM： To evaluate the effect of single nucleotide poly- morphisms of interleukin （IL）-28B, rs12979860 on progression and treatment response in chronic hepatitis C. METHODS： Patients （n = 64; 37 men, 27 women; mean...AIM： To evaluate the effect of single nucleotide poly- morphisms of interleukin （IL）-28B, rs12979860 on progression and treatment response in chronic hepatitis C. METHODS： Patients （n = 64; 37 men, 27 women; mean age, 44 ＋ 12 years） with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was per- formed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, ami- notransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured. RESULTS： A sustained virological response （SVR） was significantly associated with IL28B polymorphism （CC vs -l-r allele： odds ratio （OR）, 25; CC vs CT allele： OR, 5.4）, inflammation activity （G 〈 1 vs G 〉 1： OR, 3.9）, fibrosis （F 〈 1 vs F 〉 1： OR, 5.9）, platelet count （〉 200 × 109/L vs 〈 200 ×109/L： OR, 4.7; OR in patients with genotype CT： 12.8）, fatty liver （absence vs presence of steatosis： OR, 4.8）, insulin resistance index （〈 2.5 vs 〉 2.5： OR, 3.9）, and baseline HCV viral load （〈 106 IU/mL vs 〉 106 IU/mL： OR, 3.0）. There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance （P = 0.064） of increased fibrosis in patients with the I-I allele, and no differences in the insulin resistance index between groups of patients with CC, CT and -IF alleles （P = 0.12）. Spearman＇s rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively （P 〈 0.001）. Significant dif- ferences were found in the insulin resistance index （P = 0.01） between patients with and without steatosis. Patients with the C-I- allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon （P = 0.07）. CONCLUSION： IL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.展开更多
Crohn's disease and ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in man,are complex diseases in which genetic and environmental factors interact to promote an excessive mucosal immune res...Crohn's disease and ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in man,are complex diseases in which genetic and environmental factors interact to promote an excessive mucosal immune response directed against normal components of the bacterial microflora.There is also evidence that the pathologic process is due to defects in counterregulatory mechanisms,such as those involving the immunosuppressive cytokine transforming growth factor(TGF)-1.Indeed,studies in human IBD tissues and murine models of colitis have documented a disruption of TGF-1 signalling marked by a block in the phosphorylation of Smad3,a signalling molecule associated with the activated TGF-receptor,due to up-regulation of Smad7,an intracellular inhibitor of Smad3 phosphorylation.Knock-down of Smad7 with a specific antisense oligonucleotide restores TGF-1/Smad3 signalling,thus resulting in a marked suppression of inflammatory cytokine production and attenuation of murine colitis.These findings together with the demonstration that Smad7 antisense oligonucleotide is not toxic when administered in mice have paved the way for the development of a Smad7 antisense oligonucleotidebased pharmaceutical compound that is now ready to enter the clinics.In this article we review the available data supporting the pathogenic role of Smad7 in IBD and discuss whether and how Smad7 antisense therapy could help dampen the ongoing inflammation in IBD.展开更多
Objectives’ To observe the effects of reflux esophagitis(RE) on the lung function and alrway reactivity,and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE.Methods. Lung function measuremen...Objectives’ To observe the effects of reflux esophagitis(RE) on the lung function and alrway reactivity,and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE.Methods. Lung function measurements and airway provocation tests were performed in 31 RE patientsand 35 control subjects’ TXB, and PGF,. were determined in 20 cases of each group.Results. In RE patients the lung function was lower and the rate of AHR was higher than control sub-jects (P<0. 05). Among RE patients 25 % had higher airway sensitivity (Dminr 3u ). The TXB2 of REpatients with AHR was higher than those without AHR’ Dmin correlated significantly with TXB2 (r=0. 653, P<0. 05).Concluswhs’ RE could damage the lung function. The rate of AHR was 61 %, the high airway sensltivity was probably potential asthma, and TXB2 may play a role in the pathogenesis of AHR.展开更多
文摘Objective: To explore the characteristics of NF-闎 activation in the progress of pancreatitis, the relationship with expression of TNF- in the inflammatory reaction, and prevent the exacerbation of pancreatitis by using NAC. Method: Forty-eight rats were divided into three groups: therapy (group C), pancreatitis (group B) and control (group A). NAC served as the inhibitor of NF-闎 activation. In the time intervals of 1.5, 3.0, 6.0, 12.0 hour, NF-闎 activation was detected with flow cytometry (FCM) and the expression of TNF- mRNA and protein with in situ hybridization (ISH) and enzyme-linked immuno-sorbent assay (ELISA) respectively. Meanwhile, the level of lipase and amylase in the serum was assayed and the pathological change was evaluated. Result: NF-闎 activation in the pancreatitis group was higher than that in the control group (P<0.01), peaked at 3 hours, and was depressed by the inhibitor of NF-闎, NAC. The expression of TNF- as well as the level of lipase and amylase in the serum also rose synchronously with activation of NF-闎. In contrast to group A, it was significantly different (P<0.01) in group B. After using NAC in group C, all of these values were decreased and the in-flammatory reaction in the pancreas abated evidently. The pathology changes of the pancreas were shown to be alleviated in group C. Conclusion: First, NF-闎 activity is intensively initiated in the course of pancreatitis and shown to have closely relationship with the release of cytokines. Second, use of NAC markedly depressed NF-闎 activation. TNF- expression is down regulated by cytokines. It is suggested that NAC probably acts as a useful agent for treatment of pancreatitis by indirectly inhibiting activation of NF-闎.
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda para proyectos de investigación en salud PI-2007/32)+5 种基金"Fundación de Investigación Médica Mutua Madrileń a" (Beca Ayudas a la Investigación FMMM 2548/2008) from SpainBenito-Martínez S was supported by a research grant from "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad de investigadores" MOV-2007_JI/18), SpainCalvino M was supported by a research grant from "Instituto de Salud Carlos III" (Contrato de apoyo a la investigación en el SNS’’ CA07/00157), Spain
文摘Hepatitis C virus（HCV）-specific CD8^＋ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 （PD-1）. This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8^＋ T cells are exhausted with impairment of several effector mechanisms, such as： type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand （PD-L1）. After this blockade, HCV-specific CD8^＋ T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-l-expressing intrahepatic HCV-specific CD8^＋ T cells do not restore their effector abilities after PD-1/ PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gClq receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response aclainst HCV to succeed in clearing the infection.
基金National Natural Science Foundation of China (No. 30070299)
文摘Objective: To investigate whether bacterial DNA involving in the pathogenesis of systemic inflammatory response syndrome (SIRS) and possible mechanism. Methods: Escherichia coli DNA (EC DNA) was extracted from Escherichia coli 25922 with alkaline lysis method. The mice mortality was observed after EC DNA was injected into mice via caudal vein. The changes of serum TNF-α and IL-6 levels in rats were measured with ELISA after rats were given EC DNA. Calf thymus DNA and lipopolysaccharide (LPS) were used as the control, respectively. Results: EC DNA led mice to death with notable dose-effect relationship (LD50=11.51 mg/kg), but CT DNA didn't. The peak level of TNF-αwas lower in EC DNA group than in LPS group (P＜0. 05), though the former reaching the peak I h earlier than the latter. However, they had coordinate ability to induce IL-6 release in rats, and no significant difference was seen in serum IL-6 peak level between 2 groups. Conclusion: EC DNA leads mice to death, and induces the increases of serum TNF-αand IL-6 levels in rats. EC DNA has the effect equal to LPS in inducing SIRS by triggering cytokines cascade.
文摘The differential diagnosis of Behcet's disease(BD) from inflammatory bowel disease(IBD) is sometimes difficult and challenging.Hereby,we suggested the utility of anti-saccharomyces cerevisiae antibody(ASCA) and anti-neutrophilic cytoplasmic antibody(p-ANCA) in the differential diagnosis of BD from IBD.
文摘AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.
基金Supported by National Natural Science Foundation of China (No.39730210)
文摘Objective: To build a cell model of LPS-induced hyper- and hypo-responsiveness in macrophage cells . Methods: Macrophage cell line RAW264. 7 was pre-cultured with or without 10 ng/ml LPS for 18 h, then challenged with lipopolysaccharide(LPS) , or MDP, Zymosan, PAF, FMLP, PMA for 24 h. The levels of TNF-α , IL-1 , IL-6, IL-10 , NO and O2-, were measured. Results: LI'S pretreatment markedly inhibited TNF-a NO and IL-6 production, but increased IL-1, IL-10 and O2- release to LPS challenge. LPS pretreatment also altered macrophage responsiveness to the other stimuli. Conclusion: LPS can induce hyper- and hypo-responsiveness simultaneously in the macrophage cell lines. Changes in macrophage responsiveness depend on stimuli and effectors which are measured.
文摘Inflammatory bowel disease （IBD） results from the interaction between an individual＇s immune response and precipitant environmental factors, which generatean anomalous chronic inflammatory response in thosewho are genetically predisposed. Various feeding practices have been implicated in the origin of IBD based on epidemiological observations in developed countries, but we do not have solid evidence for the etiological role played by specific food types. IBD is associated with frequent nutritional deficiencies, thepattern and severity of which depends on the extent,duration and activity of the inflammation. Nutritional support allows these deficiencies in calories, macro and micronutrients to be rectified. Enteral nutrition is also aprimary therapy for IBD, especially for Crohn＇s disease,as it allows the inflammatory activity to be controlled,kept in remission, and Drevents or delays the need forsurgery. Nutritional support is especially important in childhood IBD as an alternative to pharmacological treatment. This report discusses the complex relationship between diet and IBD.
文摘AIM： To evaluate the effect of single nucleotide poly- morphisms of interleukin （IL）-28B, rs12979860 on progression and treatment response in chronic hepatitis C. METHODS： Patients （n = 64; 37 men, 27 women; mean age, 44 ＋ 12 years） with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was per- formed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, ami- notransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured. RESULTS： A sustained virological response （SVR） was significantly associated with IL28B polymorphism （CC vs -l-r allele： odds ratio （OR）, 25; CC vs CT allele： OR, 5.4）, inflammation activity （G 〈 1 vs G 〉 1： OR, 3.9）, fibrosis （F 〈 1 vs F 〉 1： OR, 5.9）, platelet count （〉 200 × 109/L vs 〈 200 ×109/L： OR, 4.7; OR in patients with genotype CT： 12.8）, fatty liver （absence vs presence of steatosis： OR, 4.8）, insulin resistance index （〈 2.5 vs 〉 2.5： OR, 3.9）, and baseline HCV viral load （〈 106 IU/mL vs 〉 106 IU/mL： OR, 3.0）. There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance （P = 0.064） of increased fibrosis in patients with the I-I allele, and no differences in the insulin resistance index between groups of patients with CC, CT and -IF alleles （P = 0.12）. Spearman＇s rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively （P 〈 0.001）. Significant dif- ferences were found in the insulin resistance index （P = 0.01） between patients with and without steatosis. Patients with the C-I- allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon （P = 0.07）. CONCLUSION： IL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.
基金Supported by The Fondazione "Umberto di Mario" Onlus, Romethe Broad Medical Research Foundation,No.IBD0301RGiuliani SpA,Milan,Italy
文摘Crohn's disease and ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in man,are complex diseases in which genetic and environmental factors interact to promote an excessive mucosal immune response directed against normal components of the bacterial microflora.There is also evidence that the pathologic process is due to defects in counterregulatory mechanisms,such as those involving the immunosuppressive cytokine transforming growth factor(TGF)-1.Indeed,studies in human IBD tissues and murine models of colitis have documented a disruption of TGF-1 signalling marked by a block in the phosphorylation of Smad3,a signalling molecule associated with the activated TGF-receptor,due to up-regulation of Smad7,an intracellular inhibitor of Smad3 phosphorylation.Knock-down of Smad7 with a specific antisense oligonucleotide restores TGF-1/Smad3 signalling,thus resulting in a marked suppression of inflammatory cytokine production and attenuation of murine colitis.These findings together with the demonstration that Smad7 antisense oligonucleotide is not toxic when administered in mice have paved the way for the development of a Smad7 antisense oligonucleotidebased pharmaceutical compound that is now ready to enter the clinics.In this article we review the available data supporting the pathogenic role of Smad7 in IBD and discuss whether and how Smad7 antisense therapy could help dampen the ongoing inflammation in IBD.
文摘Objectives’ To observe the effects of reflux esophagitis(RE) on the lung function and alrway reactivity,and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE.Methods. Lung function measurements and airway provocation tests were performed in 31 RE patientsand 35 control subjects’ TXB, and PGF,. were determined in 20 cases of each group.Results. In RE patients the lung function was lower and the rate of AHR was higher than control sub-jects (P<0. 05). Among RE patients 25 % had higher airway sensitivity (Dminr 3u ). The TXB2 of REpatients with AHR was higher than those without AHR’ Dmin correlated significantly with TXB2 (r=0. 653, P<0. 05).Concluswhs’ RE could damage the lung function. The rate of AHR was 61 %, the high airway sensltivity was probably potential asthma, and TXB2 may play a role in the pathogenesis of AHR.
