BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening program...BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.展开更多
BACKGROUND Clinical diagnosis of cirrhotic cardiomyopathy(CCM) often encounters challenges of lack of timeliness and disease severity, with the commonly positive indicator usually associated with advanced heart failur...BACKGROUND Clinical diagnosis of cirrhotic cardiomyopathy(CCM) often encounters challenges of lack of timeliness and disease severity, with the commonly positive indicator usually associated with advanced heart failure.AIM To explore suitable biomarkers for early CCM prediction.METHODS A total of 505 eligible patients were enrolled in this study and divided into four groups according to Child-Pugh classification: Group Ⅰ, Class A without CCM(105 cases);Group Ⅱ, Class A with CCM(175 cases);Group Ⅲ, Class B with CCM(139 cases);and Group Ⅳ, Class C with CCM(86 cases). Logistic regression and receiver operating characteristic(ROC) curve analyses were performed to determine whether red blood cell distribution width(RDW) was an independent risk factor for CCM risk. The relationships between RDW and Child-Pugh scores, Model for End-Stage Liver Disease(MELD) scores, and N-terminal pro-brain natriuretic peptide(NT-proBNP) were analyzed by Pearson correlation analysis.RESULTS A constant RDW increase was evident from Group Ⅰ to Group Ⅳ(12.54 ± 0.85, 13.29 ± 1.19, 14.30 ± 1.96, and 16.25 ± 2.13, respectively). Pearson correlation analysis showed that RDW was positively correlated with Child-Pugh scores(r = 0.642, P < 0.001), MELD scores(r = 0.592, P < 0.001), and NT-proBNP(r = 0.715, P < 0.001). Furthermore, between Group Ⅰ and Group Ⅱ, RDW was the only significant index(odds ratio: 2.175, 95% confidence interval [CI]: 1.549-3.054, P < 0.001), and it reached statistical significance when examined by ROC curve analysis(area under the curve: 0.686, 95%CI: 0.624-0.748, P < 0.001).CONCLUSION RDW can serve as an effective and accessible clinical indicator for the prediction of diastolic dysfunction in CCM, in which a numerical value of more than 13.05% may indicate an increasing CCM risk.展开更多
The Wister fat-storing cells were isolated by perfusion with collagenase and centrifugation with metrizamide density cushion technique and cultured in vitro. The fatstoring cells were confirmed by the presentation of ...The Wister fat-storing cells were isolated by perfusion with collagenase and centrifugation with metrizamide density cushion technique and cultured in vitro. The fatstoring cells were confirmed by the presentation of the lipid drop in the cytoplasm and the visualization of dismin with anti-dismin antibody by using indirect immunofluorescence method. By the videotape recorder (VIR) and the imagine analysis system, we observed the wandering immigration, the abrupt contraction of fat-storing cells with spike, then becoming a ball-like shape in its division phase. After that the cell began to extend and the contraction of these cells can be induced by the presence of 10-2 mmol/L endothelin-1 , 1 mmol/L of substance P and 2×10-5 mmol/L noradrenalin. After removal of these agents the contracted cells would become extended. All these findings indicate that the fat-storing cells have ability of contraction and movement.展开更多
Background: Numerous studies of tissues’ regeneration have confessed the recovery of damaged liver by hematopoietic stem cells. The cells act not only by cell replacement in the target organ but also by delivering tr...Background: Numerous studies of tissues’ regeneration have confessed the recovery of damaged liver by hematopoietic stem cells. The cells act not only by cell replacement in the target organ but also by delivering trophic factors that support endogenous liver regeneration. A little is known of how organ-derived signals recruit such committed cells into circulation. Objective: We investigated the roles of noninvasive mechanical percutaneous stress of cirrhotic human liver in numbers fluctuation of trophic, liver-specific alpha-fetoprotein-positive fraction of CD133-positive hematopoietic stem cells in lymphocytes of patients waiting for liver transplantation. Methods: To promote in blood the number of the alpha-fetoprotein-positive fraction of CD133-positive hematopoietic stem cells, committed to liver’ tissue, we activated mechanically the cirrhotic liver of patient by transcutaneous micro vibration received from skin-contacted electro-magnetic vibraphones generated mechanical pulses with amplitude 10 μm and smoothly changing frequency from 0.03 kHz to 18 kHz and back forth during one cycle duration 1 minute. The number of the alpha-fetoprotein-positive fraction of CD133-positive hematopoietic stem cells in lymphocytes of potential recipients was controlled by flow cytometry before and during daily sonication of skin area, which corresponds to liver projection on it. The 15 minutes cyclic sonication of the liver area performed daily for three weeks. Results: The sonication increased significantly averaged number of liver-specific alpha-fetoprotein-positive CD133-positive blood lymphocytes in 2 - 3 times compared to a base lane. The second similar sonication, the same zone after three weeks break showed differences with baseline, but it was statistically insignificant. The result was specifically related to the liver as it showed the control sonication of the backbone’s projection on the skin of a separate group of patients with cirrhotic liver from the waiting list. Conclusion: The stem cells committed to the liver recruit from the bone marrow into circulation, when organ mechanically stresses and secretes specific humoral signals to provoke of lymphopoiesis on host liver repair.展开更多
Mastocytosis is a clonal neoplastic disorder of the mast cells(MC) that can be limited to the skin(cutaneous mastocytosis) or involve one or more extracutaneous organs(systemic mastocytosis). The clinical manifestatio...Mastocytosis is a clonal neoplastic disorder of the mast cells(MC) that can be limited to the skin(cutaneous mastocytosis) or involve one or more extracutaneous organs(systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis(ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology.展开更多
基金Supported by Sara Borrell postdoctoral fellowships from Instituto de Salud Carlos Ⅲ to support ángela Rojas postdoctoral contract,Consejería de Salud y Familias,Junta de Andalucía supporting Antonio Gil-Gómez contract,PI19/01404 Grant from Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,PI19/00589/Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,and the Xeptagen,Italy,provided the ELISA kits for the measurements of SCCA-IgM.
文摘BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.
基金Supported by the Fujian Provincial Education and Scientific Research Project,No.JAT200121Fujian Provincial Health Technology Project,No.2021QNA021.
文摘BACKGROUND Clinical diagnosis of cirrhotic cardiomyopathy(CCM) often encounters challenges of lack of timeliness and disease severity, with the commonly positive indicator usually associated with advanced heart failure.AIM To explore suitable biomarkers for early CCM prediction.METHODS A total of 505 eligible patients were enrolled in this study and divided into four groups according to Child-Pugh classification: Group Ⅰ, Class A without CCM(105 cases);Group Ⅱ, Class A with CCM(175 cases);Group Ⅲ, Class B with CCM(139 cases);and Group Ⅳ, Class C with CCM(86 cases). Logistic regression and receiver operating characteristic(ROC) curve analyses were performed to determine whether red blood cell distribution width(RDW) was an independent risk factor for CCM risk. The relationships between RDW and Child-Pugh scores, Model for End-Stage Liver Disease(MELD) scores, and N-terminal pro-brain natriuretic peptide(NT-proBNP) were analyzed by Pearson correlation analysis.RESULTS A constant RDW increase was evident from Group Ⅰ to Group Ⅳ(12.54 ± 0.85, 13.29 ± 1.19, 14.30 ± 1.96, and 16.25 ± 2.13, respectively). Pearson correlation analysis showed that RDW was positively correlated with Child-Pugh scores(r = 0.642, P < 0.001), MELD scores(r = 0.592, P < 0.001), and NT-proBNP(r = 0.715, P < 0.001). Furthermore, between Group Ⅰ and Group Ⅱ, RDW was the only significant index(odds ratio: 2.175, 95% confidence interval [CI]: 1.549-3.054, P < 0.001), and it reached statistical significance when examined by ROC curve analysis(area under the curve: 0.686, 95%CI: 0.624-0.748, P < 0.001).CONCLUSION RDW can serve as an effective and accessible clinical indicator for the prediction of diastolic dysfunction in CCM, in which a numerical value of more than 13.05% may indicate an increasing CCM risk.
文摘The Wister fat-storing cells were isolated by perfusion with collagenase and centrifugation with metrizamide density cushion technique and cultured in vitro. The fatstoring cells were confirmed by the presentation of the lipid drop in the cytoplasm and the visualization of dismin with anti-dismin antibody by using indirect immunofluorescence method. By the videotape recorder (VIR) and the imagine analysis system, we observed the wandering immigration, the abrupt contraction of fat-storing cells with spike, then becoming a ball-like shape in its division phase. After that the cell began to extend and the contraction of these cells can be induced by the presence of 10-2 mmol/L endothelin-1 , 1 mmol/L of substance P and 2×10-5 mmol/L noradrenalin. After removal of these agents the contracted cells would become extended. All these findings indicate that the fat-storing cells have ability of contraction and movement.
文摘Background: Numerous studies of tissues’ regeneration have confessed the recovery of damaged liver by hematopoietic stem cells. The cells act not only by cell replacement in the target organ but also by delivering trophic factors that support endogenous liver regeneration. A little is known of how organ-derived signals recruit such committed cells into circulation. Objective: We investigated the roles of noninvasive mechanical percutaneous stress of cirrhotic human liver in numbers fluctuation of trophic, liver-specific alpha-fetoprotein-positive fraction of CD133-positive hematopoietic stem cells in lymphocytes of patients waiting for liver transplantation. Methods: To promote in blood the number of the alpha-fetoprotein-positive fraction of CD133-positive hematopoietic stem cells, committed to liver’ tissue, we activated mechanically the cirrhotic liver of patient by transcutaneous micro vibration received from skin-contacted electro-magnetic vibraphones generated mechanical pulses with amplitude 10 μm and smoothly changing frequency from 0.03 kHz to 18 kHz and back forth during one cycle duration 1 minute. The number of the alpha-fetoprotein-positive fraction of CD133-positive hematopoietic stem cells in lymphocytes of potential recipients was controlled by flow cytometry before and during daily sonication of skin area, which corresponds to liver projection on it. The 15 minutes cyclic sonication of the liver area performed daily for three weeks. Results: The sonication increased significantly averaged number of liver-specific alpha-fetoprotein-positive CD133-positive blood lymphocytes in 2 - 3 times compared to a base lane. The second similar sonication, the same zone after three weeks break showed differences with baseline, but it was statistically insignificant. The result was specifically related to the liver as it showed the control sonication of the backbone’s projection on the skin of a separate group of patients with cirrhotic liver from the waiting list. Conclusion: The stem cells committed to the liver recruit from the bone marrow into circulation, when organ mechanically stresses and secretes specific humoral signals to provoke of lymphopoiesis on host liver repair.
文摘Mastocytosis is a clonal neoplastic disorder of the mast cells(MC) that can be limited to the skin(cutaneous mastocytosis) or involve one or more extracutaneous organs(systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis(ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology.
