AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC...AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years(median) after proctocolectomy.Expression of MMPs-3,-7,-8,-9,-12 and-26 and TIMPs-1,-2 and-3 in samples was examined using immunohistochemichal methods,and another biopsy was used to evaluate the grade of histological inflammation.Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion,using a scale marking staining intensity as follows:0 = less than 20 positive cells;1 = 20-50 positive cells;2 = 50-200 positive cells;3 = over 20 positive cells.Fecal calprotectin and blood inflammatory markers [serum C-reactive protein(CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS:Of the 28 patients with pediatric onset UC,nine had not experienced pouchitis,whereas thirteen reported a single episode,and six had recurrent pouchitis(≥ 4 episodes).At the time of the study,six patients required metronidazole.In all of the others,the most recent episode of pouchitis had occurred over one month earlier,and none were on antibiotics.Only four samples depicted no sign of inflammation,and these were all from patients who had not had pouchitis.Two samples were too small to determine the grade of inflammation,but both had suffered pouchitis,the other recurrent.No sample depicted signs of colonic metaplasia.Most pouch samples showed expression of epithelial(e) and stromal(s) MMP-3(e,n = 22;s,n = 20),MMP-7(e,n = 28;s,n = 27),MMP-12(e,n = 20;s,n =24),TIMP-2(e,n = 23;s,n = 23) and MMP-3(e,n = 23;s,n = 28) but MMP-8(e,n = 0;s,n = 1),MMP-9(e,n = 0;s,n = 9) and MMP-26(e,n = 0;s,n = 3) and TIMP-1(n = 0,both) were lacking.In samples with low grade of inflammatory activity,the epithelial MMP-3 and MMP-7 expression was increased(r =-0.614 and r =-0.472,respectively,P < 0.05 in both).MMPs and TIMPs did not correlate with the markers of inflammation,fecal calprotectin,erythrocyte sedimentation rate,or CRP,with the exception of patients with low fecal calprotectin(< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMPor TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes.Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP-or TIMP-expression.CONCLUSION:The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease,but inflammation cannot be classified as a reactivation of the disease.展开更多
Objective To observe the efficacy of knee-balancing manipulation plus heat-sensitive moxibustion in treating knee osteoarthritis(KOA)and its impact on the expression of C-telopeptide of type I collagen(CTX-Ⅰ),tartrat...Objective To observe the efficacy of knee-balancing manipulation plus heat-sensitive moxibustion in treating knee osteoarthritis(KOA)and its impact on the expression of C-telopeptide of type I collagen(CTX-Ⅰ),tartrate-resistant acid phosphatase 5b(TRACP-5b),A disintegrin and metalloproteinase with thrombospondin motifs 4(ADAMTS-4),and matrix metalloproteinase 3(MMP-3).Methods A total of 134 unilateral KOA patients were randomized into a knee-balancing group,a heat-sensitive moxibustion group,and a joint intervention group.The knee-balancing group received knee-balancing Tuina(Chinese therapeutic massage)manipulation for treatment.The heat-sensitive moxibustion group received heat-sensitive moxibustion treatment.The joint intervention group received the heat-sensitive moxibustion in addition to the knee-balancing manipulation.The intervention period lasted for four weeks.After the treatment,and at the 2-week and 6-week follow-ups,the three groups were assessed using the visual analog scale(VAS)for knee joint pain and Western Ontario and McMaster Universities arthritis index(WOMAC),and clinical efficacy was also evaluated.The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3.Results The knee-balancing group had 44 participants,but one dropped out;there was no dropout case among the 44 participants in the heat-sensitive moxibustion group;among the 46 participants in the joint intervention group,two cases dropped out.After the treatment,and at the 2-week and 6-week follow-ups,the total effective rate was found higher in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.05).Compared with the baseline,the VAS and WOMAC scores and the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 decreased significantly in all three groups after treatment and at the 2-week and 6-week follow-ups(P<0.05).At the same three time points,the VAS and WOMAC scores and serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 were lower in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.001).Conclusion Either used alone or combined,the knee-balancing manipulation and heat-sensitive moxibustion therapy can improve the symptoms and down-regulate the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 in KOA patients,producing durable efficacy;nevertheless,a more significant efficacy can be achieved by combining the two methods.展开更多
基金Supported by The Academy of Finland,Finska Lkaresllskapet,Helsinki University Central Hospital Research Fund,Finnish Cultural Foundation (to Mkitalo L)Biomedicum Helsinki Foundation (to Mkitalo L),Finland+2 种基金the Swedish Research Council,Sweden (to Saarialho-Kere U)the Pivikki and Sakari Sohlberg Foundation (to Kolho KL)the Finnish Pediatric Research Foundation (to Kolho KL)
文摘AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years(median) after proctocolectomy.Expression of MMPs-3,-7,-8,-9,-12 and-26 and TIMPs-1,-2 and-3 in samples was examined using immunohistochemichal methods,and another biopsy was used to evaluate the grade of histological inflammation.Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion,using a scale marking staining intensity as follows:0 = less than 20 positive cells;1 = 20-50 positive cells;2 = 50-200 positive cells;3 = over 20 positive cells.Fecal calprotectin and blood inflammatory markers [serum C-reactive protein(CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS:Of the 28 patients with pediatric onset UC,nine had not experienced pouchitis,whereas thirteen reported a single episode,and six had recurrent pouchitis(≥ 4 episodes).At the time of the study,six patients required metronidazole.In all of the others,the most recent episode of pouchitis had occurred over one month earlier,and none were on antibiotics.Only four samples depicted no sign of inflammation,and these were all from patients who had not had pouchitis.Two samples were too small to determine the grade of inflammation,but both had suffered pouchitis,the other recurrent.No sample depicted signs of colonic metaplasia.Most pouch samples showed expression of epithelial(e) and stromal(s) MMP-3(e,n = 22;s,n = 20),MMP-7(e,n = 28;s,n = 27),MMP-12(e,n = 20;s,n =24),TIMP-2(e,n = 23;s,n = 23) and MMP-3(e,n = 23;s,n = 28) but MMP-8(e,n = 0;s,n = 1),MMP-9(e,n = 0;s,n = 9) and MMP-26(e,n = 0;s,n = 3) and TIMP-1(n = 0,both) were lacking.In samples with low grade of inflammatory activity,the epithelial MMP-3 and MMP-7 expression was increased(r =-0.614 and r =-0.472,respectively,P < 0.05 in both).MMPs and TIMPs did not correlate with the markers of inflammation,fecal calprotectin,erythrocyte sedimentation rate,or CRP,with the exception of patients with low fecal calprotectin(< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMPor TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes.Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP-or TIMP-expression.CONCLUSION:The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease,but inflammation cannot be classified as a reactivation of the disease.
文摘Objective To observe the efficacy of knee-balancing manipulation plus heat-sensitive moxibustion in treating knee osteoarthritis(KOA)and its impact on the expression of C-telopeptide of type I collagen(CTX-Ⅰ),tartrate-resistant acid phosphatase 5b(TRACP-5b),A disintegrin and metalloproteinase with thrombospondin motifs 4(ADAMTS-4),and matrix metalloproteinase 3(MMP-3).Methods A total of 134 unilateral KOA patients were randomized into a knee-balancing group,a heat-sensitive moxibustion group,and a joint intervention group.The knee-balancing group received knee-balancing Tuina(Chinese therapeutic massage)manipulation for treatment.The heat-sensitive moxibustion group received heat-sensitive moxibustion treatment.The joint intervention group received the heat-sensitive moxibustion in addition to the knee-balancing manipulation.The intervention period lasted for four weeks.After the treatment,and at the 2-week and 6-week follow-ups,the three groups were assessed using the visual analog scale(VAS)for knee joint pain and Western Ontario and McMaster Universities arthritis index(WOMAC),and clinical efficacy was also evaluated.The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3.Results The knee-balancing group had 44 participants,but one dropped out;there was no dropout case among the 44 participants in the heat-sensitive moxibustion group;among the 46 participants in the joint intervention group,two cases dropped out.After the treatment,and at the 2-week and 6-week follow-ups,the total effective rate was found higher in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.05).Compared with the baseline,the VAS and WOMAC scores and the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 decreased significantly in all three groups after treatment and at the 2-week and 6-week follow-ups(P<0.05).At the same three time points,the VAS and WOMAC scores and serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 were lower in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.001).Conclusion Either used alone or combined,the knee-balancing manipulation and heat-sensitive moxibustion therapy can improve the symptoms and down-regulate the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 in KOA patients,producing durable efficacy;nevertheless,a more significant efficacy can be achieved by combining the two methods.