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Objective@#To investigate the value of alpha-fetoprotein (AFP) level on survived hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients treated with artificial liver.@*Methods@#Clinical indicators of HBV-ACLF patients who were previously treated with plasma exchange-based artificial liver at our department were retrospectively collected. The difference of serum AFP level between the survival and the death group was compared at 30, 90 and 180 days after artificial liver treatment. The ROC curves of the subjects were plotted, and the sensitivity and specificity of AFP for the survival prediction of the patients at 30, 90 and 180 days after artificial liver surgery were calculated. AFP was divided into a high AFP group and a low AFP group using median value. AFP and postoperative survival predictive value at 30, 90, and 180 days were analyzed.@*Results@#A total of 93 cases were included in this study. The AFP of the survival group at 30, 90, and 180 days was (231.0 ± 286.2) ng / ml, (237.69 ± 297) ng / ml, (229.44 ± 286.46) ng/ml, and the death group was (76.4 ± 104.7) ng/ml, (103.13 ± 116.99) ng / ml, (136.34 ± 2.9.29) ng/ml, respectively. AFP of the death group was significantly lower than the corresponding survival group (P < 0.05). Receiver operating characteristic (ROC) curve analyses indicated that the area under the curve (AUC) and its 95% confidence interval at 30, 90, and 180 days after artificial liver surgery were 0.739 (0.611 ~ 0.867), 0.675 (0.550 ~ 0.80), 0.653 (0.524 ~ 0.781), respectively. The median serum AFP value was 110 ng/ml, and the survival analysis showed that the survival time of the high AFP group was significantly higher than the low AFP group at 30 d (P = 0.01), 90 d (P = 0.04) and 180 d (P = 0.03) after artificial liver surgery.@*Conclusion@#Serum AFP can be used as a predictor of survival for HBV-ACLF patients after artificial liver therapy and its clinical value needs to be further verified by the larger sample size.
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Liver regeneration is an important response after liver injury and necrosis to maintain liver volume and function, with the involvement of various factors and signaling pathways. This process has three main stages, i.e., the initial stage of mitosis triggered by certain factors, the proliferation stage of promoting hepatocytes to enter the cell cycle, and the termination stage of promoting liver cells to reach a certain number and the recovery of liver mass. This article introduces various factors and multiple cellular signaling pathways that promote the differentiation of liver stem cells into liver cells to restore liver volume and function and summarizes the previous research findings of our group that alpha-fetoprotein is an important serum marker for liver regeneration after liver failure. The analysis shows that in-depth studies of the occurrence and clinical application of liver regeneration will help to improve the understanding of liver regeneration, better predict the prognosis of acute and chronic liver diseases, and provide new ideas and methods for the clinical diagnosis and treatment of various advanced liver diseases.
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Objective To explore the risk of tuberculosis infection in patients with malignant tumors.Methods The sputum samples and blood samples from 396 patients with malignant tumor and 80 healthy subjects were detected by modified Roche cul-ture,real-time fluorescence quantitative PCR,colloidal gold,T cell spots(TSPOT.TB)and single immunodiffusion(SRID).Results The positive rate of the experimental group of 396 cases of malignant tumor patients with five kinds of methods for detection of Mycobacterium tuberculosis were improved Lowenstein Jensen 12.1%(48/396),real-time PCR(169/396)42.7%,colloidal gold 38.9%(154/396),TSPOT.TB 44.9%(178/396),SRID 10.4%(41/396).In the control group,the positive result was detected only by real-time fluorescent PCR 8.7%(7/80),colloidal gold 6.3%(5/80),and TSPOT.TB 27.5%(22/80).The differences of the results of the same detection method were statistically significant(P<0.01).The experimental group was grouped according to the location of the lesion,and there was no statistical difference between the indexes of each group(P>0.05).In comparison with other types of tumor,there were no statistical differences in every index of every group(P>0.05).But the positive rates of liver cancer patients were lower than those of other types of tumor,and all the positive rates of lung cancer patients were higher than those of other types of tumor.Conclusion Patients with malignant tumor is a high-risk group of TB infection.It is suggested that early screening and regular monitoring of TB infection should be done for patients with malignant tumor,so as to achieve early de-tection and early treatment.
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At present, the most effective therapeutic method for end-stage liver fibrosis is liver transplantation. However, the application of liver transplantation is limited by a shortage of liver donors, a high incidence rate of surgical complications, graft-versus-host disease, and high medical costs. Umbilical cord mesenchymal stem cell (UC-MSC) transplantation may become a promising method for the treatment of liver diseases. UC-MSCs are adult stem cells which exhibit multipotential differentiation and can differentiate into hepatic parenchymal cells. Due to their functions including immune regulation and secretion of trophic factors, UC-MSCs can inhibit immune response, promote hepatocyte regeneration, alleviate the progression of liver fibrosis, and improve liver function. In addition, compared with bone marrow mesenchymal stem cells, UC-MSCs have abundant sources, noninvasive collection, and high safety and thus they are attracting more and more attention. This article reviews the characteristics of UC-MSCs and their mechanism of action in the treatment of liver fibrosis, as well as risks of UC-MSCs therapy.
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There are not many studies on chronic hepatitis C complicated by autoimmune hepatitis, and up to now, the clinical diagnosis and treatment of such diseases still face many difficulties. Although related articles put forward some recommendations, there are no standard guidelines for diagnosis and treatment, and clinical physicians need to provide treatment for these patients based on their personal experience. This article summarizes related articles on chronic hepatitis C complicated by autoimmune hepatitis in order to provide help to clinical physicians when they face similar clinical problems in the future.
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Transjugular intrahepatic portosystemic shunt (TIPS) can effectively reduce portal hypertension, prevent recurrent esophagogastric variceal bleeding, and relieve intractable ascites. TIPS involves vessel puncture, expansion of puncture tract within the liver parenchyma, and stent implantation, and may cause various complications. The effective prevention and treatment of TIPS-related complications have become a new direction for research in TIPS. This article reviews the intraoperative and postoperative complications of TIPS and related preventive and treatment strategies.
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ObjectiveTo observe the effect of continuous blood purification (CBP) on serum inflammatory mediators in patients with severe acute pancreatitis (SAP) and multiple organ dysfunction syndrome (MODS). MethodsSixty-five SAP patients with MODS who were treated in General Hospital of Chengdu Command Area of Chinese PLA from April 2008 to December 2013 were enrolled and divided into two groups. The 33 patients in the control group received comprehensive internal medicine treatment, and the 32 patients in the treatment group received comprehensive internal medicine treatment and CBP. Changes in APACHE II score, MODS score, and the serum levels of tumor necrosis factor α (TNFα), C-reactive protein (CRP), interleukin 6 (IL-6), IL-18, platelet-activating factor (PAF), and nitric oxide (NO) after treatment were observed. Independent-samples t test was applied for comparison of continuous data between the two groups, and paired t test was applied for before-after comparison within the same group; chi-squared test was applied for comparison of categorical data between the two groups. ResultsIn both groups, APACHE II score, MODS score, and the serum levels of TNFα, CRP, IL-6, IL-18, PAF, and NO decreased significantly after treatment (all P＜0.05), and the treatment group had significantly greater decreases in these values than the control group (all P＜0.001); the survival rates in the treatment group and the control group were 90.6% (29/32) and 78.8% (26/33), respectively, with no significant difference between the two groups (χ2=1.749, P=0.186). ConclusionIn SAP patients with MODS, CBP can effectively clear the serum inflammatory mediators to block systemic inflammatory response and improve organ function, and, therefore, it is an effective method to treat SAP.
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Portal hypertension is a common clinical disease and brings a series of complications including the formation of gastrointestinal varicose veins, ascites, hepatic encephalopathy, and abdominal varicose veins. Most of these complications are related to the opening of collateral circulation after the increase in portal venous pressure. On one hand, collateral circulation helps to alleviate the high portal venous pressure, and on the other hand, it brings related complications to patients. This article reviews recent reports and studies on collateral circulation related to portal hypertension, in order to increase our knowledge of collateral circulation in portal hypertension and improve clinical diagnosis and treatment of such disease.
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ObjectiveTo analyze the efficacy of endoscopic histoacryl injection in the treatment of gastric variceal bleeding caused by regional portal hypertension. MethodsThe endoscopic features and efficacy of endoscopic histoacryl injection were examined and compared in two groups of patients admitted to our hospital from June 2012 to December 2012. One of the groups included 6 patients with gastric variceal bleeding caused by regional portal hypertension and the other group included 6 patients with gastric variceal bleeding caused by hepatitis B cirrhosis-related portal hypertension. Between-group comparison of categorical data was made by Fisher′s test. ResultsIn patients with regional portal hypertension, five of them had severe isolated gastric varices (IGV) and one had severe IGV with mild esophageal varices. All six patients with hepatitis B cirrhosis-related portal hypertension had severe IGV and the endoscopic features were similar to those of patients with regional portal hypertension. Significant differences were observed between the group with regional portal hypertension and the group with hepatitis B cirrhosis related portal hypertension in short-term response rate (1/6 vs 6/6, P=0.015) and long-term response rate (0/6 vs 5/6, P=0.015). ConclusionThe gastric varices caused by regional portal hypertension has a fast progression rate and a high bleeding risk. The efficacy of endoscopic histoacryl injection in patients with this type of gastric varices is poor.
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Liver failure is a clinical syndrome with severe disorders of liver cells for biosynthesis, detoxication, excretion, and biological transformation, which presents with coagulation disorders, jaundice, hepatic encephalopathy, and ascites. Liver failure progresses rapidly, so the prediction of clinical outcome is significant for the diagnosis and treatment. In recent years, there have been numerous reports on the prediction of clinical outcome in patients with liver failure. The study and application of serological and comprehensive models are reviewed, which provides a reference for the rational therapy for liver failure patients.
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<p><b>OBJECTIVE</b>To evaluate the agreement and correlation between hepatic vein pressure gradient (HVPG) and portal vein pressure (PVP) in patients with portal hypertension,and explore their clinical value.</p><p><b>METHODS</b>A total of 46 patients with portal hypertension were directly measured the free hepatic pressure, wedged hepatic pressure, portal vein pressure before and after TIPS therapy. The agreement and correlation of HVPG and PVP were analyzed, and explore their clinical value.</p><p><b>RESULTS</b>There is no significant agreement or correlation between HVPG and PVP in 5 patients, whose third hilar have large communicating branches between portal vein and Inferior vena cava, or with obvious umbilical vein opened. The HVPGs were significantly agreed with portal vein pressure in other 41 patients. There is no significant difference of HVPG or PVP between earlyTIPS and not early-TIPS groups. In addition, the portal vein pressures after TIPS were significantly decreased compared with that before TIPS.</p><p><b>CONCLUSION</b>The HVPG can well show the PVP except these with obvious communicating branches between portal vein and Inferior vena cava in third hilar, and TIPS can effectively decrease the portal vein pressure in patients with portal hypertension.</p>
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Humans , Hepatic Veins , Hypertension, Portal , Portal Vein , Vena Cava, Inferior , Venous PressureABSTRACT
OBJECTIVE@#To investigate the function of bone marrow mesenchymal stem cells (BMSCs) with over-expressed matrix metalloproteinase 1 (MMP1) on liver fibrosis.@*METHODS@#Fifty SD male rats were randomly divided into 4 groups: recombinant adenovirus Adhuman MMP-1(hMMP-1)-enhanced green fluorescent protein (EGFP) transfected BMSCs group (Group A, n=10), Ad-EGFP transfected BMSCs group (Group B, n=10), liver fibrosis group (Group C, n=15), and a normal group (Group D, n=15). The liver fibrosis model was formed by subcutaneous injection of the mixed liquor of carbon tetrachloride (CCL4) and vegetable oil. After 10 weeks, the model of liver fibrosis was formed. Group A and B were administered the transfected BMSCs via the tail veins, while Group C and D were administered normal saline. After 3 weeks, the rats were sacrificed. The body weight, liver weight, liver function, liver fibrosis indexes and liver pathological changes were tested.@*RESULTS@#Compared with the control group, the rats administered BMSCs with over-expressed MMP1 showed a significant improvement in the body weight, liver weight and plasma albumin (ALB) (P<0.05), and a significant reduction in the plasma alanine aminotransferase, total bilirubin, hyaluronic acid, laminin and procollagen III (P<0.05). Hematoxylin-eosin staining confirmed that the degree of liver fibrosis was significantly ameliorated under average visual fields (P<0.05).@*CONCLUSION@#The repair ability of BMSCs on liver fibrosis can be enhanced by over-expression of hMMP-1.
Subject(s)
Animals , Male , Rats , Adenoviridae , Carbon Tetrachloride , Green Fluorescent Proteins , Hematopoietic Stem Cells , Cell Biology , Liver Cirrhosis , Therapeutics , Matrix Metalloproteinase 1 , Genetics , Metabolism , Rats, Sprague-Dawley , TransfectionABSTRACT
BACKGROUND:Matrix metaloproteinase-1 can degrade extracelular matrix, which is mainly colagen type I, and has the potential to reverse fibrosis tissue. OBJECTIVE:To construct the recombinant adenovirus vector containing human matrix metaloproteinase-1 (hMMP-1) gene with GatewayTM Clone Technology, and observe the capacity of degrading colagen type IIIin vitro. METHODS: The gene hMMP-1 was amplified by using PCR from the pcDNA3.1 plasmid and was cut down by the double endonuclease. The linear gene fragment was connected to the entry vector pENTERTM 1A. Then the entry clone and the destination vectors pJTI? R4 Dest CMV-N-EmGFP pA Vector recombined using the LR reaction to form the expression clone pAd-hMMP-1-eGFP. The linear pAd-hMMP-1-eGFP cut down by endonucleasePac I was transfected into HEK293A cels to packaging the Ad-hMMP-1-eGFP. The transfected situation was observed under a fluorescence microscope, the target protein expression was detected by western-blot assay and RT-PCR. Cels can be divided into three groups: blank control group: HEK293A cels, AD-EGFP group: HEK293A cels were infected by Ad-eGFP, AD-HMMP1-EGF group: HEK293A cels were infected by Ad-hMMP1-eGFP and colagen type III. The content of colagen type III was detected by ELISA kits after 24, 48 and 72 hours. RESULTS AND CONCLUSION: It was confirmed that the entry vector and the destination vector both contained hMMP-1 target gene by restriction analysis and sequencing. The green fluorescent protein was observed in the 293A cels transfected by the Ad-hMMP-1-eGFP at 4 days. The fluorescence intensity was the highest at 10 days. The virus was colected at 12 days, the viral titer was determined as 4.84 × 1010 PFU/mL, the target protein was efficient expressionvia western-blot assay. Blank control group and AD-EGFP group had no obvious change of colagen content with the extension of time. The rate of colagen degradation in AD-HMMP1-EGFP group was 24%, 56% and 81% respectively at 24, 48, 72 hours. AD-HMMP1-EGFP group degraded colagen significantly compared with the other two groups (P < 0.01). The recombinant adenovirus vector containing hMMP-1 was successfuly constructed by using the Gateway technology, this method was more efficient and specific than with the traditional methods. The hMMP1 degraded colagen type III significantlyin vitro.
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BACKGROUND:A large number of experiments have confirmed that bone marrow mesenchymal stem cells can differentiate into hepatocytes under the induction of cytokines and specific micro-environment, and have been widely used in clinical alternative treatment for terminal liver disease, but the optimal inducing conditions are unclear. OBJECTIVE:To explore the possibility and validity of differentiation of rat bone marrow mesenchymal stem cells into hepatocytes with a culture system containing salidroside and cholestatic rat serum in vitro. METHODS:Bone marrow mesenchymal stem cells were isolated by plastic adherence from the whole bone marrow of health rats, and cellphenotypes were identified using the flow assay;cholestatic serum was prepared by common bile duct ligation. Passage 3 bone marrow mesenchymal stem cells were randomly divided into three groups for in vitro induction by the different culture systems:blank control group:basic medium plus 5%cholestatic serum;salidroside group:basic medium plus 5%cholestatic serum plus 30 μmol/L salidroside;positive control group:basic medium plus 5%cholestatic serum plus 20 μg/L hepatocyte growth factor. Changes of cellmorphology during culture time were observed in each group, reverse transcription-PCR assay and western blot assay were used to expression of hepatocyte-specific proteins. RESULTS AND CONCLUSION:The bone marrow mesenchymal stem cells highly expressed CD90, CD105, but did not express CD45, CD14, CD34, and CD79a. Polygonal and binucleate cells appeared in the three groups during the procedure of induction. The mRNA and protein expression of alpha-fetoprotein and albumin emerged in the three groups on the 7th day;in the same period, the lowest expression ratio was in the blank control group (P0.05). Combination of salidroside and cholestatic serum can effectively induce bone marrow mesenchymal stem cells differentiating into hepatocytes.
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Objective To investigate the effect of Salidroside in inducing apoptosis of rat hepatic stellate cells (HSC) stimulated by acetaldehyde and to observe the changes of c- Jnk N- terminal kinase (JNK) activity.Methods HSC stimulated by acetaldehyde were cultured in vitro and were treated with different concentrations of Salidroside.Apoptotic rate was analyzed by flow cytometry and the activity of phosphorylating JNK was measured by Western blot method.Results Salidroside in different concentrations (1.0,1.5,2.0 mg/mL) suppressed the activity of JNK in a dose- effect manner.Average light density was 35.8? 3.4,24.9? 2.7 and 3.4? 0.9 in Salidroside groups, which differed from that in acetaldehyde group( 48.6? 4.8; P