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With the improvement of living standard, the incidence rate of nonalcoholic fatty liver disease (NAFLD) is gradually increasing year by year and its age of onset tends to become younger, but its pathogenesis remains unclear. Macrophages are important cells involved in the pathogenesis of NAFLD and have attracted great attention. This article elaborates on the origin and classification of liver macrophages, the role of macrophages in liver inflammation and related activation mechanism, and the drugs targeting macrophages, in order to provide a reference for the clinical treatment of NAFLD.
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Objective:To explore the risk factors, clinical features, endoscopic characteristics and the efficacy of antiviral therapy in ulcerative colitis (UC) patients complicated with cytomegaloviremia (CMV) and Epstein-Barr (EB) viremia.Methods:From April 1, 2014 to January 31, 2019, at The Second Hospital of Hebei Medical University, a total of 320 UC patients hospitalized at the Department of Gastroenterology were enrolled. According to the pathogens, the patients were divided into four groups: complicated with CMV and EB viremia group ( n=35), only complicated with CMV viremia group ( n=33), only complicated with EB viremia group ( n=52) and without CMV and EB viremia group ( n=200). Clinical features and the efficacy of antiviral therapy of the patients were retrospectively analyzed. Multivariate logistic regression was used to analyze the risk factors of UC complicated with CMV and EB viremia. Kruskal-Wallis H test, Chi-square test and Fisher exact test were used for statistical analysis. Results:The proportion of patients of age>60 years old (42.86%, 15/35), the rate of glucocorticoid use (51.43%, 18/35) within three months before onset and the inefficacy rate of glucocorticoid treatment (22.86%, 8/35) of UC complicated with CMV and EB viremia group were all higher than those of UC without CMV and EB viremia group (14.00%, 28/200; 24.50%, 49/200; 1.00%, 2/200), and the differences were statistically significant ( χ2=17.062, 10.598 and 29.769; all P<0.01). However, there were no statistically significant differences between UC complicated with CMV and EB viremia group and UC without CMV and EB viremia group in gender, and treatment of 5-aminosalicylic acid (5-ASA), azathioprine and infliximab within three months before onset (all P>0.05). The proportion of patients with fever (54.29%, 19/35), abdominal pain (91.43%, 32/35), hematochezia (94.29%, 33/35), weight loss (28.57%, 10/35), severe disease activity (94.29%, 33/35), total colon involvement (91.43%, 32/35), serum albumin less than 30 g/L (71.43%, 25/35) and hemoglobin less than 100 g/L (48.57%, 17/35) of UC complicated with CMV and EB viremia group were all higher than those of UC without CMV and EB viremia group (13.50%, 27/200; 43.00%, 86/200; 44.00%, 88/200; 13.50%, 27/200; 38.00%, 76/200; 65.00%, 130/200; 18.00%, 36/200 and 18.50%, 37/200), and the differences were statistically significant ( χ2=31.475, 27.945, 32.930, 5.100 and 40.194, Fisher exact test, χ2=44.242 and 15.220, all P<0.01). However, there were no statistically significantl differences in clinical classification and disease course (all P>0.05). The incidence rates of deep ulcer (45.71%, 16/35), irregular ulcer (42.86%, 15/35) and longitudinal ulcer (8.53%, 3/35) under endoscopy of UC complicated with CMV and EB viremia group were significantly higher than those of UC without CMV and EB viremia group (1.50%, 3/200; 3.50%, 7/200 and 1.00%, 2/200), and the differences were statistically significant ( χ2=72.521 and 49.837, Fisher exact test, all P<0.01). The incidence rates of deep ulcer and irregular ulcer under endoscopy of UC complicated with CMV and EB viremia group were higher than those of UC only complicated with EB viremia group (15.38%, 8/52 and 11.54%, 6/52), and the differences were statistically significant ( χ2=9.663 and 11.206, P=0.002 and 0.001). The results of Multivariate Logistic regression analysis showed that severe disease activity, serum albumin level less than 30 g/L, and deep ulcer and irregular ulcer under endoscopy were risk factors of UC patients complicated with CMV and EB viremia (odds ratio=48.519, 44.352, 53.432 and 39.989, 95% confidence interval 9.057 to 587.669, 4.499 to 437.245, 3.302 to 864.670 and 3.418 to 467.910, all P<0.05). The improvement rate of antiviral therapy in UC complicated with CMV and EB viremia group (73.53%, 25/34) was significantly lower than those of UC only complicated with CMV group (96.88%, 31/32) and UC only complicated EB viremia group (95.65%, 44/46), and the differences were statistically significant ( χ2=6.989 and 6.310, P=0.008 and 0.012). Conclusions:UC patients with severe disease activity, serum albumin level less than 30 g/L, and deep ulcer and irregular ulcer under endoscopy are more likely to develop CMV and EB viremia. The more severe the disease, the worse the treatment response, so it is necessary to strengthen the screening to CMV and EB virus infection in UC patients.
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Objective@#To explore the risk factors of cytomegalovirus (CMV) infection or reactivation in ulcerative colitis (UC) patients.@*Methods@#We performed a search at the databases of Pubmed, Cochrane, Embase, CNKI, Wanfang, SinoMede and VIP up to March 2017. A search strategy was constructed by using a combination of the following words: "inflammatory bowel disease or IBD" or "ulcerative colitis or UC" and "cytomegalovirus or CMV" . Literature was screened according to the inclusion and exclusion criteria and statistics was analyzed using RevMan 5.3 software provided by Cochrane collaboration network and analyzed using Stata 12.0 software to evaluate publication bias.@*Results@#After searching and screening, we included 18 case-control studies finally. Meta-analysis showed that the risk of CMV infection or reactivation in severe UC was 1.45 times that in mild to moderate UC and the risk in whole colon was 1.54 times that of patients with left colon and rectum with the pooled OR values as 1.45 (1.02-2.05) and 1.54 (1.05-2.27). The risk of CMV infection in middle-aged patients with UC was higher than that in young patients with the pooled MD values of 4.60(2.13-7.07). The therapies with glucocorticoid and immunosuppressive agents such as azathioprine, cyclosporine and methotrexate were high risk factors of CMV infection or reactivation in UC patients, with the pooled OR values as 3.87 (2.70-5.53) and 2.07 (1.29-3.32), but the duration of UC, treatment with 5-Amino salicylic acid/salazosulfapyridine (5-ASA/SASP) and infliximab had no statistically significant correlation with the CMV infection or reactivation in UC patients, with the pooled OR values as -1.20 (-2.64-0.24), 0.94 (0.61-1.42) and 1.50 (0.65-3.44).@*Conclusions@#In patients with severe UC, whole colon lesions and the therapy with glucocorticoid and immunosuppressive agents were the risk factors of CMV infection or reactivation. The risk of CMV infection or reactivation in middle-aged patients was higher than that in young patients.
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Objective@#To analyze the clinical features and risk factors of ulcerative colitis (UC)complicated with Epstein-Barr(EB)-viremia and the effect of antiviral therapy on the remission of the symptoms.@*Methods@#From April 2014 to January 2018, data of 239 UC patients hospitalized at the Department of Gastroenterology of Second Hospital of Hebei Medical University were collected. The patients were divided into EB-viremia group (trial group, n=43) and non-EB-viremia group (control group, n=196) according to EB virus-DNA detection. The general condition, clinical characteristics and therapeutic efficacy of the two groups were compared. The risk factors and the effect of antiviral therapy on the remission of symptoms of UC complicated with EB-viremia were analyzed. Chi-square test and logistic analysis were used for statistical analysis.@*Results@#There were no significant differences in gender, age, clinical type, lesion range, the proportion of patients treated with 5-aminosalicylic acid or corticosteroids, the percentage of patients with diarrhea and bloody stool, the proportion of patients with spontaneous bleeding, platy ulcer and longitudinal ulcer under colonoscopy, the course of disease or Mayo score between the trial group and control group (all P>0.05). The proportions of patients with smoking history and severe disease, treatment with azathioprine and 6-mertocapurine (6-MP), treatrnent with infliximab, symptoms of fever or abdominal pain and deep and large ulcer under colonoscopy in the trial group were all higher than those in the control group, and the differences were all statistically significant (χ2=5.304, 6.608, 6.718, 6.939, 8.783, 4.493 and 5.425, all P<0.05). The results of multivariate logistic regression analysis showed that smoking history and treatment with azathioprine and 6-MP were risk factors of UC complicated with EB-viremia (OR=2.801 and 9.343, 95%CI 1.170 to 6.703 and 1.749 to 49.922, P=0.021 and 0.009). The improvement rates of the trial group and control group were 79.1%(34/43) and 95.4%(187/196), respectively. There was a significant difference in the improvement rate between the two groups (χ2=10.551, P=0.001). In the trial group, 12 patients (27.9%) received ganciclovir treatment, fonr patients (9.3%) had foscarnet sodium treatment, 21 patients (48.8%) were treated with the combination of these two medications and six cases (14.0%) did not received any antiviral treatment. After three weeks, the improvement cases of the above regimens were 8, 4, 16 and 6, respectively. There were no statistically significant differences in the improvement rate of patients with and without antiviral treatment, further more, no difference was found in the improvement rate of patients with different antiviral treatments (all P>0.05).@*Conclusions@#Smoking history and purine treatment are risk factors of UC complicated with EB-viremia.
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Objective To analyze the clinical features and risk factors of ulcerative colitis (UC) complicated with Epstein-Barr(EB)-viremia and the effect of antiviral therapy on the remission of the symptoms.Methods From April 2014 to January 2018,data of 239 UC patients hospitalized at the Department of Gastroenterology of Second Hospital of Hebei Medical University were collected.The patients were divided into EB-viremia group (trial group,n =43) and non-EB-viremia group (control group,n =196) according to EB virus-DNA detection.The general condition,clinical characteristics and therapeutic efficacy of the two groups were compared.The risk factors and the effect of antiviral therapy on the remission of symptoms of UC complicated with EB-viremia were analyzed.Chi-square test and logistic analysis were used for statistical analysis.Results There were no significant differences in gender,age,clinical type,lesion range,the proportion of patients treated with 5-aminosalicylic acid or corticosteroids,the percentage of patients with diarrhea and bloody stool,the proportion of patients with spontaneous bleeding,platy ulcer and longitudinal ulcer under colonoscopy,the course of disease or Mayo score between the trial group and control group (all P ＞ 0.05).The proportions of patients with smoking history and severe disease,treatment with azathioprine and 6-mertocapurine (6-MP),treatrnent with infliximab,symptoms of fever or abdominal pain and deep and large ulcer under colonoscopy in the trial group were all higher than those in the control group,and the differences were all statistically significant (x2 =5.304,6.608,6.718,6.939,8.783,4.493 and 5.425,all P ＜ 0.05).The results of multivariate logistic regression analysis showed that smoking history and treatment with azathioprine and 6-MP were risk factors of UC complicated with EB-viremia (OR =2.801 and 9.343,95％ CI 1.170 to 6.703 and 1.749 to 49.922,P =0.021 and 0.009).The improvement rates of the trial group and control group were 79.1％ (34/43) and 95.4％ (187/196),respectively.There was a significant difference in the improvement rate between the two groups (x2 =10.551,P =0.001).In the trial group,12 patients (27.9％) received ganciclovir treatment,four patients (9.3％) had foscamet sodium treatment,21 patients (48.8％) were treated with the combination of these two medications and six cases (14.0％) did not received any antiviral treatment.After three weeks,the improvement cases of the above regimens were 8,4,16 and 6,respectively.There were no statistically significant differences in the improvement rate of patients with and without antiviral treatment,further more,no difference was found in the improvement rate of patients with different antiviral treatments (all P ＞ 0.05).Conclusions Smoking history and purine treatment are risk factors of UC complicated with EB-viremia.
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Objective@#To explore the effects of macrophages with high expression of TL1A on the activation and proliferation of HSCs in vitro. @*Methods@#The Bone marrow-derived macrophages (BMMs) and peritoneal macrophages (PMs) from wild type (WT) and myeloid-overexpressed TL1A transgenic mice were isolated, differentiated and activated. HSCs were harvested from activated macrophages culture supernatant (CM). HSCs were detected by immunofluorescence and real-time Q-PCR. And the proliferation was detected by CCK-8 and BrdU assay kit. The levels of IL-1β and PDGF-BB in macrophage culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). @*Results@#BMMs-derived CM-intervention HSCs were used to detect the expression of α-smooth muscle actin (α-SMA) on the 2nd, 4th and 6th day respectively by immunofluorescence method. There was no significant difference between the two groups on the 2 nd and the 6th day, P > 0.05; On day 4, the CM/Tg group was significantly higher than that of CM/WT group, P < 0.01; the results of CMs derived from PMs were consistent with the above trend. The expression of α-SMA mRNA on the 2nd, 4th and 6th day was detected by real-time Q-PCR method using BM-derived CMs. No significant difference was found between the groups on the 2nd day (P > 0.05).α-SMA mRNA increased further on the 4th and 6th day, and the level of CM/Tg in CM/Tg group was significantly higher than that in CM/WT group (P < 0.05). The detection results of CMs derived from PMs were consistent with the above trend. The results of CCK-8 assay and BrdU assay showed that the proliferation rate of HSCs in CM Tg group was significantly higher than that in CM/WT group (P < 0.01). The CMs derived from PMs were used to interfere with HSCs. And the results were consistent with the above trend. For BMMs, the levels of IL-1β and PDGF-BB in the lipopolysaccharide (LPS) + IFNγ/Tg culture supernatant were significantly higher than those in the LPS+IFNγ/WT group (P < 0.01). For the culture supernatants of PMs Liquid test results consistent with the above trend. @*Conclusion@#Macrophages with high expression of TL1A could enhance the activation and proliferation of HSCs by increasing the secretion of IL-1β and PDGF-BB.
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Background:Ulcerative colitis(UC)patients are the high risk population of cytomegalovirus(CMV)infection. CMV infection may aggravate the disease progression of UC,and the prognosis of UC patients with CMV infection may be improved by antiviral therapy. Aims:To systematically evaluate the effects of CMV infection and antiviral therapy on prognosis of UC patients. Methods:PubMed,Cochrane Library,Embase,CNKI,Wanfang,SinoMed and VIP database were retrieved to collect the case-control studies studying the effects of CMV infection and antiviral therapy on prognosis of UC patients. Meta-analysis was conducted by RevMan 5.3 software. Results:Twenty case-control studies were enrolled. Meta-analysis showed that UC patients in CMV infection group were more serious(OR=1.62,95% CI:1.13-2.33),and had larger intestinal lesions(OR=0.63,95% CI:0.43-0.92),higher risks of steroid dependence/resistance(OR=6.13, 95% CI:1.98-19.00)and colectomy(OR=1.64,95% CI:1.14-2.36). Antiviral therapy for UC patients with CMV infection significantly improved the early clinical remission rate(OR =2.08,95% CI:1.03-4.17),decreased risk of colectomy(OR=2.12,95% CI:1.06-4.22). Conclusions:CMV infection can aggravate the progress of UC,enlarge the extent of intestinal lesion,increase the risks of steriod dependence/resistance and colectomy. Antiviral therapy significantly improves the early clinical remission rate,and decreases the risk of colectomy.
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Objective To investigate the effects of tumor necrosis factor-related ligand-1A(TL1A)on activation of T helper 9(Th9)cells of colonic tissues in chronic experimental colitis mice.Methods The chronic experimental colitis mice model was established with drinking dextran sulfate sodium salt(DSS).A total of 32 lymphocytes TL1A highly expressed mice and wild type(WT)mice were divided into WT control group, transgene control group,WT modeling group and transgene modeling group.The mice of control groups were administrated with distilled water. The mice of modeling groups received 3% DSS in drinking water discontinuously.The mice were sacrificed on 29 days after modeling.Body mass was measured,length of colon was recorded,scores of gross colon and the disease activity index(DAI)were calculated.The colonic morphological changes were observed by hematoxylin-eosin(H-E)staining.The lamina propria mononuclear cells(LPMC)were isolated and the number of Th9 cells was tested by flow cytometry.The levels of interleukin-9(IL-9)in serum and LPMC were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of IL-9 protein and mRNA of the colonic tissues were measured by Western blotting and real-time polymerase chain reaction(PCR),respectively.T test and single factor analysis of variance were performed for statistical analysis.Results The percentage of body mass loss of WT modeling group was lower than that of transgene modeling group(16.2% ± 1.0% vs 18.9% ± 1.2%),and the difference was statistically significant(t=4.90, P<0.05).The scores of gross colon,DAI and pathology of transgene modeling group were all higher than those of WT modeling group(2.80 ± 0.64 vs 1.60 ± 0.31,2.55 ± 0.20 vs 1.58 ± 0.17,and 11.85 ± 0.86 vs 9.50 ± 0.79),and the differences were statistically significant(t=4.77,10.45 and 5.69,all P<0.05).The number of LPMC in transgene modeling group was higher than that of WT modeling group(3.70×106± 0.28×106vs 2.65×106± 0.32 × 106)and the difference was statistically significant(t= 6.98,P< 0.05).The percentage of Th9 in total CD4+T cells of LPMC in colonic tissues of transgene modeling group was higher than that of WT modeling group(0.54% ± 0.04% vs 0.23% ± 0.03%),and the difference was statistically significant(t= 17.54,P< 0.05).The serum IL-9 level of transgene modeling group was higher than that of WT modeling group((170.23 ± 5.69)pg/mL vs(150.62 ± 6.45)pg/mL),and the difference was statistically significant(t= 6.50,P< 0.05).The level of IL-9 secreted by LMPC of transgene modeling group was higher than that of WT modeling group((265.21 ± 8.76)pg/mL vs (237.58 ± 10.24)pg/mL),and the difference was statistically significant(t= 5.80,P< 0.05).The expressions of IL-9 protein and mRNA of transgene modeling group were higher than those of WT modeling group(1.31 ± 0.09 vs 1.18 ± 0.03,and 8.26 ± 1.13 vs 2.25 ± 0.29,respectively),and the differences were statistically significant(t=3.88 and 14.57,both P< 0.05).Conclusion TL1A high expression in lymphocytes can promote Th9 cells differentiation and IL-9 secretion which involved in the genesis of chronic experimental colitis.
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BACKGROUND:Cirrhosis is a long-term consequence of chronic hepatic injury, which has no effective therapy. Mesenchymal stem cels have been shown to play a potential role in the treatment of liver fibrosis/cirrhosis. OBJECTIVE:To investigate the therapeutic effect and mechanism of human umbilical cord-derived mesenchymal stem cels on CCl4 induced liver fibrosis/cirrhosis in rats. METHODS:A CCl4-induced liver fibrotic/cirrhotic rat model was used, and human umbilical cord-derived mesenchymal stem cels were injectedvia the tail vein after modeling. Liver biochemical profile was measured by Beckman Coulter analyzer. Histopathological changes were assessed by Sirius red staining. The expressions of colagen type I, colagen type III, matrix metaloproteinases-2 and tissue inhibitor of matrix metaloproteinases-2 protein and mRNA in liver tissues were observed by immunohistochemistry, western blot and real-time PCR, respectively. RESULTS AND CONCLUSION:Liver biochemical profile indicated the transplantation of human umbilical cord-derived mesenchymal stem cels could improve the liver function of rats with liver fibrosis and cirrhosis. After cel transplantation, except 1-week cel transplantation group, the expressions of the matrix metaloproteinases-2 mRNA and protein were significantly increased, while the expressions of colagen type I, colagen type III and tissue inhibitor of matrix metaloproteinases-2 mRNA and protein significantly decreased, compared with the corresponding model groups. Human umbilical cord-derived mesenchymal stem cels play a role in the treatment of liver fibrosis and cirrhosis through upregulating the expression of matrix metaloproteinases-2 and lowering the expression of inhibitor of matrix metaloproteinases-2. With the continued presence of pathogenic factors, human umbilical cord-derived mesenchymal stem cel transplantation cannot reverse liver fibrosis or cirrhosis, and only delay the process of liver fibrosis or cirrhosis.
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With the improvement of living standard, the incidence rate of nonalcoholic fatty liver disease (NAFLD) is gradually increasing year by year and its age of onset tends to become younger, but its pathogenesis remains unclear. Macrophages are important cells involved in the pathogenesis of NAFLD and have attracted great attention. This article elaborates on the origin and classification of liver macrophages, the role of macrophages in liver inflammation and related activation mechanism, and the drugs targeting macrophages, in order to provide a reference for the clinical treatment of NAFLD.