OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis(NASH)include liver steatosis,inflammation,and fibrosis.Fibrosis is the most severe and significant pathological feature in NASH.Effective drug...OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis(NASH)include liver steatosis,inflammation,and fibrosis.Fibrosis is the most severe and significant pathological feature in NASH.Effective drug treatment could reverse early liver fibrosis and is of significance to prevent NASH from progressing into cirrhosis and liver cancer.Identification of drug targets for NASH treatment has been an active research area and is essential for the development of anti-NASH medications.Naringenin(NGN)is a flavonoid compound rich in citrus fruits.Our preliminary data demonstrated that NGN reduced diet-induced lipid accumulation and inflammation in the mouse liver,but whether NGN can attenuate liver fibrosis of NASH is not known.METHODS To study the effect of NGN on NASH fibrosis.WT mice were fed with high fat diet(HFD)and injected intraperitoneally 20%carbon tetrachloride at the same time for 8 weeks to induce NASH,and NGN was administrated by gavage in the meantime.In vitro,LO2 cells and LX2 cells were stimulated by oleic acid(OA)combined with lipopolysaccharide(LPS),respectively.RESULTS Treating the WT mice with NGN 100 mg·kg^(-1)·d-1 significantly attenuated hepatic lipid accumulation,hepatic fibrosis,plasma ALT and AST levels,inhibited protein expression of p-ERK,p-FoxO3a in the mouse livers.In vitro,on OA and LPS stimulated LO2 or LX2 cells,NGN significantly promoted apoptosis of activated hepatic stellate cells while inhibited apoptosis of hepatocytes.Mechanism study indicated that NGN inhibited MAPK pathway and promoted activation of FoxO3a,consequently promoted apoptosis of the activated LX2 cells and inhibited liver fibrosis.CONCLUSION NGN preventes NASH fibrosis via regulating MAPK/FoxO3a pathway,thus promoting apoptosis of the activated hepatic stellate cells.展开更多
Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macol...Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rgl is the most pharmacological active one. Based on prior experi- mental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rgl is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the under- lying possible mechanisms. Methods C57BL/6 mice were given oral consumption of 6 g · kg^-1 alcohol 1 h after treated with Rgl （ 10, 20 and 40 mg · kg^-1） or dexamethasone （ 1 mg · kg^-1） for 9 consecutive days. Biochemi- cal analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results According to our data, Rgl treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but re- stored in Rgl-treated groups. Overproductive inflammatory cytokines were also suppressed by Rgl in alcohol-intoxi- cated mouse livers. In addition, changes of GR related NF-KB pathway, including phospho-IKB-ot, were also mod- ulated to normal levels. Conclusion This study demonstrates that Rgl might promote GR mediating the repression of NF-KB and inhibit the inflammatory reactions in alcoholic hepatitis.展开更多
Alcoholic hepatitis(AH)was first reported in 1961 as an acute disease in alcoholics with severe clinical syndromes including jaundice,anorexia,nausea,upper abdominal pain,hepatomegaly and fever etc.1 Today,it is gener...Alcoholic hepatitis(AH)was first reported in 1961 as an acute disease in alcoholics with severe clinical syndromes including jaundice,anorexia,nausea,upper abdominal pain,hepatomegaly and fever etc.1 Today,it is generally accepted that severe AH is a form of acute-on-chronic liver failure in patients with underlying chronic alcohol-related liver disease(ALD).The detailed diagnosis of AH was recently defined by the National Institute on Alcohol Abuse and Alcoholism(NIAAA)-supported consortia and published in 2016.2 The first diagnostic criterion is alcohol drinking history,which includes heavy drinking>5 years,recent drinking>6 months with<60 days of abstinence before the onset of jaundice,and men with>4 drinks(50-60 g)/day,and women with>3 drinks(40 g)/day.The typical clinical sign is jaundice with some non-specific signs and symptoms including malaise,tender hepatomegaly,decompensation(ascites,encephalopathy,bacterial infection,variceal bleeding).展开更多
Serological methods were used to determine the cause of fulminant hepatitisin 207 patients. They were admitted to the isolation wards of 4 hospitals inShenyang between 1986-1990. The final diagnoses were: hepatitis ty...Serological methods were used to determine the cause of fulminant hepatitisin 207 patients. They were admitted to the isolation wards of 4 hospitals inShenyang between 1986-1990. The final diagnoses were: hepatitis type A 4 cas-es (2.0%), type B 144 cases (69.4% ),superinfections with A and B 3 cases (1.5%), hepatitis non-A non-B (NANB) 51 cases (24.6%), type D 2 cases (1.0%), type E 2 cases (1.0%) and cytomegalovirus (CW) infection 1 case (0.5%). The risk factors were found to be concerned with type D and several typesuper infections (prognosis poor).展开更多
Hepatitis E is caused by hepatitis E virus （HEV）, which has been classified into four genotypes. Genotypes 3 and 4 are regarded as zoonotic pathogens. Accumulating researches indicate that genotype 4 is the main HEV...Hepatitis E is caused by hepatitis E virus （HEV）, which has been classified into four genotypes. Genotypes 3 and 4 are regarded as zoonotic pathogens. Accumulating researches indicate that genotype 4 is the main HEV strain circulating in China, and there are high levels of seropositive pigs and human in some provinces of China. In this study, serum samples from pigs and from human occupationally exposed to pigs were obtained from pig farms in Guangdong Province, in subtropical southern China, in order to investigate for the first time the prevalence of anti-HEV immunoglobulin G （IgG） in the region. Antibodies against HEV were detected by Enzyme-Linked Immunosorbent Assay （ELISA） using a commercially marketed kit. The results showed that high numbers of pigs （74/94; 78.7%） and human （50/94; 53.2%） from three pig farms in Guangdong Province were positive for anti-HEV IgG. The correlation coefficient relating the prevalence in pigs and human on different farms was 0.920. The seropositive rate in males （human） was 48.8% （20/41） and that in females was 47.7% （9/19）, which showed no statistically significant difference. These data indicated that there was a high prevalence of anti-HEV antibodies in pigs and in human with occupational exposure to pigs. The risk of infection with HEV in both human and pigs in Guangdong Province appeared to be age-dependent, to a certain extent. This study provided basic data for further researches on HEV and was a reminder that more attention should be paid to HEV infection both in pigs and workers on pig farms in the study region.展开更多
用RT-PCR方法检测辽东湾几个重点沿岸海域表层海水和几种经济贝类样品中甲肝病毒的分布。结果表明,6个重点沿岸海域表层海水中均检出甲肝病毒(Hepatitis A virus,HAV),6种经济贝类样品中有4个样品检出甲肝病毒。检测结果显示,辽东湾某...用RT-PCR方法检测辽东湾几个重点沿岸海域表层海水和几种经济贝类样品中甲肝病毒的分布。结果表明,6个重点沿岸海域表层海水中均检出甲肝病毒(Hepatitis A virus,HAV),6种经济贝类样品中有4个样品检出甲肝病毒。检测结果显示,辽东湾某些重点沿岸海域受陆源生活污水影响严重,有关部门应加强海洋环境和海产贝类卫生安全监测和管理,以避免引发甲型肝炎暴发流行。展开更多
Objective To observe the value of real-time shear wave elastography(SWE)combined with biochemical indicators for evaluating liver injury in patients with chronic kidney disease(CKD).Methods Totally 210 patients with C...Objective To observe the value of real-time shear wave elastography(SWE)combined with biochemical indicators for evaluating liver injury in patients with chronic kidney disease(CKD).Methods Totally 210 patients with CKD(CKD group)and 64 healthy subjects(control group)were retrospectively enrolled.Patients in CKD group were further divided into CKD1—5 subgroups according to CKD stages.SWE parameters of liver and kidney,including mean value,the maximum value and the median value of Young's modulus(EQI mean,EQI max and EQI med)were compared between CKD subgroups and control group.Spearman correlation analysis were performed to explore the correlations of liver and kidney SWE parameters with CKD stage,as well as of liver SWE parameters with biochemical indicators.Multivariate logistic regression analysis was used to screen independent predictors of liver injury in CKD patients.Receiver operating characteristic curves were drawn,the area under the curves(AUC)were calculated to evaluate the efficacy of the independent predictors alone and their combination for assessing liver injury in CKD patients.Results Significant differences of liver and kidney SWE parameters were found among CKD subgroups and control group(all P≤0.001).Pairwise comparison showed that liver SWE parameters in CKD5 subgroup and liver EQI max in CKD4 subgroup were all higher than those in control group(all P<0.003).Kidney SWE parameters in CKD3 subgroup were all higher than those in control group,while in CKD4 subgroup were all higher than those in control group and CKD1—3 subgroup(all P<0.003).Kidney EQI mean and EQI med in CKD5 subgroup were all higher than those in control group and CKD1—4 subgroup,while kidney EQI max in CKD5 subgroup were higher than those in control group and CKD1—3 subgroup(all P<0.003).Liver and kidney SWE parameters were lowly-moderately and positively correlated with CKD stages(r=0.364—0.665,all P<0.001).Liver SWE parameters of CKD were weakly and positively correlated with alkaline phosphatase(ALP)(r=0.229—0.248,all P<0.01).Theγ-glutamyl transferase,ALP and liver EQI max were all independent predictors of liver injury in CKD patients(all P<0.01),with AUC for evaluating liver injury in CKD patients alone of 0.645,0.756 and 0.741,respectively,lower than that of their combination(0.851,all P<0.01).Conclusion Real-time SWE combined with liver function indicators could reflect degree of liver injury in patients with different CKD stages.展开更多
OBJECTIVE To explore the role of gecko crude peptides(GCPs)in the proliferation,apoptosis,migration and lymphangiogenesis of human hepatocellular carcinoma cells(Hep G2)and human lymphaticendothelial cells(HLECs)in vi...OBJECTIVE To explore the role of gecko crude peptides(GCPs)in the proliferation,apoptosis,migration and lymphangiogenesis of human hepatocellular carcinoma cells(Hep G2)and human lymphaticendothelial cells(HLECs)in vitro.METHODS The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay was used to evaluate the anti-proliferative effect of GCPs and si RNA-VEGF-C on Hep G2 cells,Hoechst 33258 staining and flow cytometry were performed to analyze cycle and apoptosis.The migration and invasion ability of cells were assayed by transwell chamber experiment and wound-healing assay.The protein and m RNA expressions of vascular endothelial growth factor-C(VEGF-C)and CXC chemokine receptor-4(CXCR4)were detected by q-PCR,immunofluorescence,Western blot.The protein expressions of the extracellular signal regulated kinase(ERKI/2),c-Jun N-terminal kinase(JNK),p38-mitogen activated protein kinases(p38 MAPK),serine/threonine kinase(Akt)and phosphatidylinositol-3-kinase(PI3K)were detected by western blot.The anti-lymphangiogenesis effect of GCPs on the HLECs was analyzed using an in vitro tube-formation assay.The protein and m RNA expressions of vascular endothelial growth factor receptor-3(VEGFR-3)and stromal cell-derived factor-1(SDF-1)were detected by q-PCR,Western blot.RESULTS GCPs and si RNA-VEGF-C inhibited Hep G2 proliferation,invasion and migration,and the most obvious inhibitory effect was both synergistic effects.Thus,GCPs suppressed HLECs proliferation,migration and tubelike structure formationin a dose-dependent manner,and had inhibitory effect of tumor-induced lymphangiogenesis in vitro.Additionally,we found that GCPs and si RNA-VEGF-C decreased the expressions of MMP-2,MMP-9,VEGF-C,CXCR4,phospho-ERK1/2,phospho-P38,phospho-JNK and PI3K in Hep G2 cells.Moreover,GCPs had a dose-dependent depressive effecton the expressions of VEGFR-3,SDF-1 in HLECs.CONCLUSION The low expression of VEGF-C mediated by si RNA-VEGF-C and GCPs inhibit tumor proliferation,invasion and migrationby suppressing the MAPK signaling pathway through reduced levels of VEGF-C,and GCPs inhibit tumor lymphangiogenesis by suppressing the CXCR4/SDF-1 signaling pathway through suppressed VEGF-C/VEGFR-3.展开更多
OBJECTIVE Hepatic fibrosis is a wound-healing response for injury.Activated hepatic stellate cells(HSCs)are the preferred targets of anti-hepatic fibrotic therapies.cucurbitacin E(CuE)is,one well-known natural compoun...OBJECTIVE Hepatic fibrosis is a wound-healing response for injury.Activated hepatic stellate cells(HSCs)are the preferred targets of anti-hepatic fibrotic therapies.cucurbitacin E(CuE)is,one well-known natural compound derived from traditional Chinese medicine,used in Asian countries for the prevention and treatment of hepatic disease.Therefore,the present study elucidated the mechanism of CuE on inducing apoptosis and attenuating hepatic fibrosis towards activated HSCs.METHODS The murine HSC(tHSC/Cl-6)cell line were incubated in 96-well plates and treated with TNF-αand CuE at various concentrations and indicated times.Cell viability was assessed with MTT assay.Another,t-HSC/Cl-6 were incubated in 6-well plates and also treated with TNF-α,CuE,AICAR or metformin for the indicated time and concentration.Cell protein and mRNA were prepared using kit and relevant signaling were detected by Western blotting and RT-PCR.RESULTS CuE inhibited cell proliferation of activated HSC/T-6cells in concentration-and time-dependent manner.CuE triggered the activation of caspase-3,cleaved the PARP,ration of bcl-2/bax,and cytochrom c protein in a time-and concentration-dependent manner.CuE decreased p-Erk/MAPK without effects on p-p38 and p-JNK.CuE inhibited the protein and mRNA expressions ofα-SMA,TIMP-1 and collagenⅠ in activated HSC-T6.CuE broadly blocked p-PI3 K,p-Akt,p-mTOR and p-p70S6 Kexpressions.CuE significantly increased phosphorylated AMPK expression as well as AICAR and metoformin.And metformin showed significantly higher activation of AMPK than AICAR.Ability of CuE on activation of AMPK was between AICAR and metformin.It′s also found that CuE significantly decreased p-mTOR as well as AICAR and metformin.CONCLUSION CuE could modulate HSC survival and activation as a potential anti-fibrotic agent for liver fibrosis treatment.The findings demonstrate that CuE induced HSC apoptosis via ERK/MAPK and PI3K/Akt-AMPK-mTOR signaling.展开更多
OBJECTIVE To investigate the mechanism of SIRT1/AMPK signaling pathway between hepatocytes and hepatic stellate cells(HSCs).METHODS Normal human Chang liver cells and human hepatic stellate cell line,LX-2 cells were t...OBJECTIVE To investigate the mechanism of SIRT1/AMPK signaling pathway between hepatocytes and hepatic stellate cells(HSCs).METHODS Normal human Chang liver cells and human hepatic stellate cell line,LX-2 cells were treated with SRT1720(10μmol·L^(-1))and AICAR(500μmol·L^(-1))prior to ethanol(50 mmol·L^(-1)) for 24 and 48 h.Cell viability was analyzed by methyl thiazolyl tetrazolium assay.SIRT1,AMPK and p-AMPK m RNA levels for 24 h and 48 h were analyzed by RT-PCR,SIRT1,AMPK and p-AMPK protein expressions in the supernatant at 24 and 48 h was detected by Western blot.RESULTS SRT1720 and AICAR effectively decreased LX-2 cell viabilities and exhibited scarcely little toxicity in human Chang liver cells.SRT1720 and AICAR attenuated collagen-I,α-smooth muscle actin(α-SMA)levels,activated liver kinase B-1(LKB1)and AMPK phosphorylation in ethanol treated LX-2 cells.Meanwhile,SRT1720 and AICAR enhanced SIRT1 expression mediated by ethanol both in Chang liver cells and LX-2 cells.Furthermore,SRT1720 and AICAR suppressed the expression of sterol regulatory element-binding protein-1(SREBP-1)to regulate fatty acid synthesis.CONCLUSION SIRT1 agonist and AMPK agonist blocked the crosstalk between hepatocytes and HSCs via SIRT1/AMPK signaling pathway to modulate hepatocytes accumulation of lipid and HSCs activation.展开更多
A simple and effective route for the synthesis of mibolerone was described starting from the estr-5(10)-en-3,17-dione in four steps with the overall yield of 47.0 %.Thus,two methods for key intermediate methylnorandro...A simple and effective route for the synthesis of mibolerone was described starting from the estr-5(10)-en-3,17-dione in four steps with the overall yield of 47.0 %.Thus,two methods for key intermediate methylnorandrost were investigated:one(method A)starting from estr-4-en-3,17-dione underwent 3-keto group protected with ethyl orthoformate to give 3-ethoxy-3,5-dien-estr-17-one,the other(method B)from estr-5(10)-en-3,17-dione and protected 3-keto group to give 3,3-dimethoxy-estr-5(10)-7-one in a mild acidic condition.Then,two intermediates were subsequently reacted with methyllithium followed by a mild hydrolytic procedure and gave methylnorandrost with total yield 25.0% and 86.0 %,respectively.In the preparation of 6-dehydrogenation product of methylnorandrost,two procedures(method C and method D)were investigated:one was the protected 17α-methyl-17β-hydroxy 3,5-enol ethers estrendiene brominated and the resulting 6-bromo-19-methylnortestosterone was then immediately dehydrohaloenated to give 6-dehydro-19-methylnortestosterone,the total yield only reaches 36.0%;the other was directly dehydrogenated with chloranil and the yield reaches 75.6% under the optimum conditions:in refluxing tetrahydrofuran,the molar ratio of methylnorandrost to chloranil is 0.66 and reaction time of 5 h.The titled compound and intermediates were characterized by 1H and 13C NMR,IRMS and elemental analysis.展开更多
OBJECTIVE To explore the therapeutic effects and underlying mechanisms of velvet antler polypeptides(VVAPs)in CCl4-induced experimental hepatic fibrosis in rats.METHODS Anti-hepatic fibrosis properties of VAPs were te...OBJECTIVE To explore the therapeutic effects and underlying mechanisms of velvet antler polypeptides(VVAPs)in CCl4-induced experimental hepatic fibrosis in rats.METHODS Anti-hepatic fibrosis properties of VAPs were tested by Subcutaneous injection(SC)into male Wistar rats of CCl4- induced experimental hepatic fibrosis.After SC injections for 45 consecutive days at doses of 5mg·kg-1(low dose,VAPsL),10mg·kg-1(mid-dose,VAPsM)and 20mg·kg-1(high-dose,VAPsH),the rats were sacrificed and the various indicators were evaluated and tested.Observed hepatic cells degeneration and necrosis,inflammatory infiltration and levels of serum enzymes to assess treatment of VAPs;The expression levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),MDA,and hydroxyproline(HYP)in liver tissue were analyzed;RT-PCR analysis was carried out to detect the expression levels of matrix metalloproteinases2(MMP-2)and tissue inhibitor of metalloproteinases 1(TIMP-1)in liver tissue.RESULTS VAPs has obvious anti-hepatic fibrosis effects.Hepatocyte swelling,fatty degeneration was significantly reduced,reducing infiltration of inflammatory cells.Release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)decreased significantly,reduction of hyaluronic acid(HA)and laminin(LN)obviously,at the same time,the content of total protein and albumin increased significantly in serum.Activity of SOD and GSH-Px was significantly raised and the content of MDA and HYP was reduced significantly in liver tissue.Expression levels of MMP-2and TIMP-1 mRNA in liver were decreased significantly.These improvements were more significant in high-dos and mid-dose groups(P<0.05 or P<0.01 vs model group).CONCLUSION These findings suggest VAPs can significant treat the hepatic fibrosis,which may be due to protect liver cells and improve liver functions by hydroxyl radical scavenging activity and great effect of antioxidation,and decrease the gene expression of MMP-2,improving exist-environment of liver cells and decreasing the gene expression of TIMP-1,prompting degradation of extracellular matrix.展开更多
文摘OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis(NASH)include liver steatosis,inflammation,and fibrosis.Fibrosis is the most severe and significant pathological feature in NASH.Effective drug treatment could reverse early liver fibrosis and is of significance to prevent NASH from progressing into cirrhosis and liver cancer.Identification of drug targets for NASH treatment has been an active research area and is essential for the development of anti-NASH medications.Naringenin(NGN)is a flavonoid compound rich in citrus fruits.Our preliminary data demonstrated that NGN reduced diet-induced lipid accumulation and inflammation in the mouse liver,but whether NGN can attenuate liver fibrosis of NASH is not known.METHODS To study the effect of NGN on NASH fibrosis.WT mice were fed with high fat diet(HFD)and injected intraperitoneally 20%carbon tetrachloride at the same time for 8 weeks to induce NASH,and NGN was administrated by gavage in the meantime.In vitro,LO2 cells and LX2 cells were stimulated by oleic acid(OA)combined with lipopolysaccharide(LPS),respectively.RESULTS Treating the WT mice with NGN 100 mg·kg^(-1)·d-1 significantly attenuated hepatic lipid accumulation,hepatic fibrosis,plasma ALT and AST levels,inhibited protein expression of p-ERK,p-FoxO3a in the mouse livers.In vitro,on OA and LPS stimulated LO2 or LX2 cells,NGN significantly promoted apoptosis of activated hepatic stellate cells while inhibited apoptosis of hepatocytes.Mechanism study indicated that NGN inhibited MAPK pathway and promoted activation of FoxO3a,consequently promoted apoptosis of the activated LX2 cells and inhibited liver fibrosis.CONCLUSION NGN preventes NASH fibrosis via regulating MAPK/FoxO3a pathway,thus promoting apoptosis of the activated hepatic stellate cells.
文摘Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rgl is the most pharmacological active one. Based on prior experi- mental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rgl is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the under- lying possible mechanisms. Methods C57BL/6 mice were given oral consumption of 6 g · kg^-1 alcohol 1 h after treated with Rgl （ 10, 20 and 40 mg · kg^-1） or dexamethasone （ 1 mg · kg^-1） for 9 consecutive days. Biochemi- cal analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results According to our data, Rgl treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but re- stored in Rgl-treated groups. Overproductive inflammatory cytokines were also suppressed by Rgl in alcohol-intoxi- cated mouse livers. In addition, changes of GR related NF-KB pathway, including phospho-IKB-ot, were also mod- ulated to normal levels. Conclusion This study demonstrates that Rgl might promote GR mediating the repression of NF-KB and inhibit the inflammatory reactions in alcoholic hepatitis.
文摘Alcoholic hepatitis(AH)was first reported in 1961 as an acute disease in alcoholics with severe clinical syndromes including jaundice,anorexia,nausea,upper abdominal pain,hepatomegaly and fever etc.1 Today,it is generally accepted that severe AH is a form of acute-on-chronic liver failure in patients with underlying chronic alcohol-related liver disease(ALD).The detailed diagnosis of AH was recently defined by the National Institute on Alcohol Abuse and Alcoholism(NIAAA)-supported consortia and published in 2016.2 The first diagnostic criterion is alcohol drinking history,which includes heavy drinking>5 years,recent drinking>6 months with<60 days of abstinence before the onset of jaundice,and men with>4 drinks(50-60 g)/day,and women with>3 drinks(40 g)/day.The typical clinical sign is jaundice with some non-specific signs and symptoms including malaise,tender hepatomegaly,decompensation(ascites,encephalopathy,bacterial infection,variceal bleeding).
文摘Serological methods were used to determine the cause of fulminant hepatitisin 207 patients. They were admitted to the isolation wards of 4 hospitals inShenyang between 1986-1990. The final diagnoses were: hepatitis type A 4 cas-es (2.0%), type B 144 cases (69.4% ),superinfections with A and B 3 cases (1.5%), hepatitis non-A non-B (NANB) 51 cases (24.6%), type D 2 cases (1.0%), type E 2 cases (1.0%) and cytomegalovirus (CW) infection 1 case (0.5%). The risk factors were found to be concerned with type D and several typesuper infections (prognosis poor).
基金Supported by the National Key R&D Program(2016YFD0500707)Department of Education of Guangdong Province(YQ2015030)the Industry Technology System of Modern Agriculture Construction Fund of China(CARS-36)
文摘Hepatitis E is caused by hepatitis E virus （HEV）, which has been classified into four genotypes. Genotypes 3 and 4 are regarded as zoonotic pathogens. Accumulating researches indicate that genotype 4 is the main HEV strain circulating in China, and there are high levels of seropositive pigs and human in some provinces of China. In this study, serum samples from pigs and from human occupationally exposed to pigs were obtained from pig farms in Guangdong Province, in subtropical southern China, in order to investigate for the first time the prevalence of anti-HEV immunoglobulin G （IgG） in the region. Antibodies against HEV were detected by Enzyme-Linked Immunosorbent Assay （ELISA） using a commercially marketed kit. The results showed that high numbers of pigs （74/94; 78.7%） and human （50/94; 53.2%） from three pig farms in Guangdong Province were positive for anti-HEV IgG. The correlation coefficient relating the prevalence in pigs and human on different farms was 0.920. The seropositive rate in males （human） was 48.8% （20/41） and that in females was 47.7% （9/19）, which showed no statistically significant difference. These data indicated that there was a high prevalence of anti-HEV antibodies in pigs and in human with occupational exposure to pigs. The risk of infection with HEV in both human and pigs in Guangdong Province appeared to be age-dependent, to a certain extent. This study provided basic data for further researches on HEV and was a reminder that more attention should be paid to HEV infection both in pigs and workers on pig farms in the study region.
文摘用RT-PCR方法检测辽东湾几个重点沿岸海域表层海水和几种经济贝类样品中甲肝病毒的分布。结果表明,6个重点沿岸海域表层海水中均检出甲肝病毒(Hepatitis A virus,HAV),6种经济贝类样品中有4个样品检出甲肝病毒。检测结果显示,辽东湾某些重点沿岸海域受陆源生活污水影响严重,有关部门应加强海洋环境和海产贝类卫生安全监测和管理,以避免引发甲型肝炎暴发流行。
文摘Objective To observe the value of real-time shear wave elastography(SWE)combined with biochemical indicators for evaluating liver injury in patients with chronic kidney disease(CKD).Methods Totally 210 patients with CKD(CKD group)and 64 healthy subjects(control group)were retrospectively enrolled.Patients in CKD group were further divided into CKD1—5 subgroups according to CKD stages.SWE parameters of liver and kidney,including mean value,the maximum value and the median value of Young's modulus(EQI mean,EQI max and EQI med)were compared between CKD subgroups and control group.Spearman correlation analysis were performed to explore the correlations of liver and kidney SWE parameters with CKD stage,as well as of liver SWE parameters with biochemical indicators.Multivariate logistic regression analysis was used to screen independent predictors of liver injury in CKD patients.Receiver operating characteristic curves were drawn,the area under the curves(AUC)were calculated to evaluate the efficacy of the independent predictors alone and their combination for assessing liver injury in CKD patients.Results Significant differences of liver and kidney SWE parameters were found among CKD subgroups and control group(all P≤0.001).Pairwise comparison showed that liver SWE parameters in CKD5 subgroup and liver EQI max in CKD4 subgroup were all higher than those in control group(all P<0.003).Kidney SWE parameters in CKD3 subgroup were all higher than those in control group,while in CKD4 subgroup were all higher than those in control group and CKD1—3 subgroup(all P<0.003).Kidney EQI mean and EQI med in CKD5 subgroup were all higher than those in control group and CKD1—4 subgroup,while kidney EQI max in CKD5 subgroup were higher than those in control group and CKD1—3 subgroup(all P<0.003).Liver and kidney SWE parameters were lowly-moderately and positively correlated with CKD stages(r=0.364—0.665,all P<0.001).Liver SWE parameters of CKD were weakly and positively correlated with alkaline phosphatase(ALP)(r=0.229—0.248,all P<0.01).Theγ-glutamyl transferase,ALP and liver EQI max were all independent predictors of liver injury in CKD patients(all P<0.01),with AUC for evaluating liver injury in CKD patients alone of 0.645,0.756 and 0.741,respectively,lower than that of their combination(0.851,all P<0.01).Conclusion Real-time SWE combined with liver function indicators could reflect degree of liver injury in patients with different CKD stages.
基金supported by Medical Science and Technology Research Project of Henan Province(142102310031)
文摘OBJECTIVE To explore the role of gecko crude peptides(GCPs)in the proliferation,apoptosis,migration and lymphangiogenesis of human hepatocellular carcinoma cells(Hep G2)and human lymphaticendothelial cells(HLECs)in vitro.METHODS The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay was used to evaluate the anti-proliferative effect of GCPs and si RNA-VEGF-C on Hep G2 cells,Hoechst 33258 staining and flow cytometry were performed to analyze cycle and apoptosis.The migration and invasion ability of cells were assayed by transwell chamber experiment and wound-healing assay.The protein and m RNA expressions of vascular endothelial growth factor-C(VEGF-C)and CXC chemokine receptor-4(CXCR4)were detected by q-PCR,immunofluorescence,Western blot.The protein expressions of the extracellular signal regulated kinase(ERKI/2),c-Jun N-terminal kinase(JNK),p38-mitogen activated protein kinases(p38 MAPK),serine/threonine kinase(Akt)and phosphatidylinositol-3-kinase(PI3K)were detected by western blot.The anti-lymphangiogenesis effect of GCPs on the HLECs was analyzed using an in vitro tube-formation assay.The protein and m RNA expressions of vascular endothelial growth factor receptor-3(VEGFR-3)and stromal cell-derived factor-1(SDF-1)were detected by q-PCR,Western blot.RESULTS GCPs and si RNA-VEGF-C inhibited Hep G2 proliferation,invasion and migration,and the most obvious inhibitory effect was both synergistic effects.Thus,GCPs suppressed HLECs proliferation,migration and tubelike structure formationin a dose-dependent manner,and had inhibitory effect of tumor-induced lymphangiogenesis in vitro.Additionally,we found that GCPs and si RNA-VEGF-C decreased the expressions of MMP-2,MMP-9,VEGF-C,CXCR4,phospho-ERK1/2,phospho-P38,phospho-JNK and PI3K in Hep G2 cells.Moreover,GCPs had a dose-dependent depressive effecton the expressions of VEGFR-3,SDF-1 in HLECs.CONCLUSION The low expression of VEGF-C mediated by si RNA-VEGF-C and GCPs inhibit tumor proliferation,invasion and migrationby suppressing the MAPK signaling pathway through reduced levels of VEGF-C,and GCPs inhibit tumor lymphangiogenesis by suppressing the CXCR4/SDF-1 signaling pathway through suppressed VEGF-C/VEGFR-3.
基金The project supported by National Natural Science Foundation of China(81260497,81460564)Science and Technology Department of Jilin Province Youth Scientific Research Fund Project(201201075)
文摘OBJECTIVE Hepatic fibrosis is a wound-healing response for injury.Activated hepatic stellate cells(HSCs)are the preferred targets of anti-hepatic fibrotic therapies.cucurbitacin E(CuE)is,one well-known natural compound derived from traditional Chinese medicine,used in Asian countries for the prevention and treatment of hepatic disease.Therefore,the present study elucidated the mechanism of CuE on inducing apoptosis and attenuating hepatic fibrosis towards activated HSCs.METHODS The murine HSC(tHSC/Cl-6)cell line were incubated in 96-well plates and treated with TNF-αand CuE at various concentrations and indicated times.Cell viability was assessed with MTT assay.Another,t-HSC/Cl-6 were incubated in 6-well plates and also treated with TNF-α,CuE,AICAR or metformin for the indicated time and concentration.Cell protein and mRNA were prepared using kit and relevant signaling were detected by Western blotting and RT-PCR.RESULTS CuE inhibited cell proliferation of activated HSC/T-6cells in concentration-and time-dependent manner.CuE triggered the activation of caspase-3,cleaved the PARP,ration of bcl-2/bax,and cytochrom c protein in a time-and concentration-dependent manner.CuE decreased p-Erk/MAPK without effects on p-p38 and p-JNK.CuE inhibited the protein and mRNA expressions ofα-SMA,TIMP-1 and collagenⅠ in activated HSC-T6.CuE broadly blocked p-PI3 K,p-Akt,p-mTOR and p-p70S6 Kexpressions.CuE significantly increased phosphorylated AMPK expression as well as AICAR and metoformin.And metformin showed significantly higher activation of AMPK than AICAR.Ability of CuE on activation of AMPK was between AICAR and metformin.It′s also found that CuE significantly decreased p-mTOR as well as AICAR and metformin.CONCLUSION CuE could modulate HSC survival and activation as a potential anti-fibrotic agent for liver fibrosis treatment.The findings demonstrate that CuE induced HSC apoptosis via ERK/MAPK and PI3K/Akt-AMPK-mTOR signaling.
基金supported by National Natural Science Foundation of China(81700523)
文摘OBJECTIVE To investigate the mechanism of SIRT1/AMPK signaling pathway between hepatocytes and hepatic stellate cells(HSCs).METHODS Normal human Chang liver cells and human hepatic stellate cell line,LX-2 cells were treated with SRT1720(10μmol·L^(-1))and AICAR(500μmol·L^(-1))prior to ethanol(50 mmol·L^(-1)) for 24 and 48 h.Cell viability was analyzed by methyl thiazolyl tetrazolium assay.SIRT1,AMPK and p-AMPK m RNA levels for 24 h and 48 h were analyzed by RT-PCR,SIRT1,AMPK and p-AMPK protein expressions in the supernatant at 24 and 48 h was detected by Western blot.RESULTS SRT1720 and AICAR effectively decreased LX-2 cell viabilities and exhibited scarcely little toxicity in human Chang liver cells.SRT1720 and AICAR attenuated collagen-I,α-smooth muscle actin(α-SMA)levels,activated liver kinase B-1(LKB1)and AMPK phosphorylation in ethanol treated LX-2 cells.Meanwhile,SRT1720 and AICAR enhanced SIRT1 expression mediated by ethanol both in Chang liver cells and LX-2 cells.Furthermore,SRT1720 and AICAR suppressed the expression of sterol regulatory element-binding protein-1(SREBP-1)to regulate fatty acid synthesis.CONCLUSION SIRT1 agonist and AMPK agonist blocked the crosstalk between hepatocytes and HSCs via SIRT1/AMPK signaling pathway to modulate hepatocytes accumulation of lipid and HSCs activation.
基金Project(50573019) support by the National Natural Science Foundation of China
文摘A simple and effective route for the synthesis of mibolerone was described starting from the estr-5(10)-en-3,17-dione in four steps with the overall yield of 47.0 %.Thus,two methods for key intermediate methylnorandrost were investigated:one(method A)starting from estr-4-en-3,17-dione underwent 3-keto group protected with ethyl orthoformate to give 3-ethoxy-3,5-dien-estr-17-one,the other(method B)from estr-5(10)-en-3,17-dione and protected 3-keto group to give 3,3-dimethoxy-estr-5(10)-7-one in a mild acidic condition.Then,two intermediates were subsequently reacted with methyllithium followed by a mild hydrolytic procedure and gave methylnorandrost with total yield 25.0% and 86.0 %,respectively.In the preparation of 6-dehydrogenation product of methylnorandrost,two procedures(method C and method D)were investigated:one was the protected 17α-methyl-17β-hydroxy 3,5-enol ethers estrendiene brominated and the resulting 6-bromo-19-methylnortestosterone was then immediately dehydrohaloenated to give 6-dehydro-19-methylnortestosterone,the total yield only reaches 36.0%;the other was directly dehydrogenated with chloranil and the yield reaches 75.6% under the optimum conditions:in refluxing tetrahydrofuran,the molar ratio of methylnorandrost to chloranil is 0.66 and reaction time of 5 h.The titled compound and intermediates were characterized by 1H and 13C NMR,IRMS and elemental analysis.
基金The project supported by National Natural Science Foundation of China(U1204826)
文摘OBJECTIVE To explore the therapeutic effects and underlying mechanisms of velvet antler polypeptides(VVAPs)in CCl4-induced experimental hepatic fibrosis in rats.METHODS Anti-hepatic fibrosis properties of VAPs were tested by Subcutaneous injection(SC)into male Wistar rats of CCl4- induced experimental hepatic fibrosis.After SC injections for 45 consecutive days at doses of 5mg·kg-1(low dose,VAPsL),10mg·kg-1(mid-dose,VAPsM)and 20mg·kg-1(high-dose,VAPsH),the rats were sacrificed and the various indicators were evaluated and tested.Observed hepatic cells degeneration and necrosis,inflammatory infiltration and levels of serum enzymes to assess treatment of VAPs;The expression levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),MDA,and hydroxyproline(HYP)in liver tissue were analyzed;RT-PCR analysis was carried out to detect the expression levels of matrix metalloproteinases2(MMP-2)and tissue inhibitor of metalloproteinases 1(TIMP-1)in liver tissue.RESULTS VAPs has obvious anti-hepatic fibrosis effects.Hepatocyte swelling,fatty degeneration was significantly reduced,reducing infiltration of inflammatory cells.Release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)decreased significantly,reduction of hyaluronic acid(HA)and laminin(LN)obviously,at the same time,the content of total protein and albumin increased significantly in serum.Activity of SOD and GSH-Px was significantly raised and the content of MDA and HYP was reduced significantly in liver tissue.Expression levels of MMP-2and TIMP-1 mRNA in liver were decreased significantly.These improvements were more significant in high-dos and mid-dose groups(P<0.05 or P<0.01 vs model group).CONCLUSION These findings suggest VAPs can significant treat the hepatic fibrosis,which may be due to protect liver cells and improve liver functions by hydroxyl radical scavenging activity and great effect of antioxidation,and decrease the gene expression of MMP-2,improving exist-environment of liver cells and decreasing the gene expression of TIMP-1,prompting degradation of extracellular matrix.
