BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associa...BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.展开更多
A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANC...A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were in effective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates thatulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients, with additional advantages of having no noticeable side-effects and less financial burden.展开更多
Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcrip...Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcripts detected in the maternal pool of RNA increased at the mid-blastula transition, decreased dramatically during gastrulation and increased again during neurulation and axis elongation. Interestingly, the decrease during gastrulation was not seen in LiCl treated (dorsalized) embryos. Whole mount in situ hybridization of TIMP-3 using DIG-labeled RNA probes demonstrated that the transcripts were present in all dorsal tissues during embryogenesis, but were prominent only in head structures starting at stage 35. Overexpression of TIMP-3 through transgenesis and RNA injections led to devel- opmental abnormalities and death. Both overexpression strategies resulted in post-gastrulation perturbation including those to neural and head structures, as well as truncated axes. However, RNA injections resulted in more severe early defects such as failure of neural tube closure, and transgenesis caused truncated axes and head abnormalities. No transgenic embryo expressing TIMP-3 survived past stage 40.展开更多
基金the Science-Technology Planning Project of Guangxi,No.Guike-AD19245174Guangxi Training Program for Medical High-level Academic Leaders,No.6 of Guiweikejiaofa[2020]-15+3 种基金Bose Talent Highland,No.2020-3-2Building Projects from the Key Laboratory of Molecular Pathology(Hepatobiliary Diseases)of Guangxi,No.Guiweikejiaofa[2020]-17the Key Laboratory of Tumor Molecular Pathology of Guangxi Colleges and Universities,No.Guijiaokeyan[2022]-10Clinical Key Specialty Building Project(For Pathology)of Guangxi,No.Guiweiyifa[2022]-21.
文摘BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.
基金Supported by National Natural Science Foundation of China, No. 30570829
文摘A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were in effective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates thatulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients, with additional advantages of having no noticeable side-effects and less financial burden.
文摘Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcripts detected in the maternal pool of RNA increased at the mid-blastula transition, decreased dramatically during gastrulation and increased again during neurulation and axis elongation. Interestingly, the decrease during gastrulation was not seen in LiCl treated (dorsalized) embryos. Whole mount in situ hybridization of TIMP-3 using DIG-labeled RNA probes demonstrated that the transcripts were present in all dorsal tissues during embryogenesis, but were prominent only in head structures starting at stage 35. Overexpression of TIMP-3 through transgenesis and RNA injections led to devel- opmental abnormalities and death. Both overexpression strategies resulted in post-gastrulation perturbation including those to neural and head structures, as well as truncated axes. However, RNA injections resulted in more severe early defects such as failure of neural tube closure, and transgenesis caused truncated axes and head abnormalities. No transgenic embryo expressing TIMP-3 survived past stage 40.
