AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METH...AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METHODS： The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA （HBV DNA） level and hepatitis B e antigen （HBeAg） were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS： During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio： 95.74 （12.13-891.31）, P 〈 0.0001], male sex [odds ratio： 7.61 （2.20-47.95）; P = 0.006], and higher Iogzo HBV DNA [odds ratio： 4.69 （1.16-20.43）; P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio： 26.51 （2.36-381.47）; P = 0.007], presence of precore mutants [odds ratio： 4.23 （1.53-19.58）, P = 0.02] and presence of basal core promoter mutants [odds ratio： 2.93 （1.24-7.57）; P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION： Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.展开更多
Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed ...Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.展开更多
BACKGROUND Chronic hepatitis C virus(HCV)infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood.Clearance of HCV by antivirals results in host immune modification,which may...BACKGROUND Chronic hepatitis C virus(HCV)infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood.Clearance of HCV by antivirals results in host immune modification,which may interfere with immune-mediated cancer surveillance.Identifying HCV patients who remain at risk of hepatocellular carcinoma(HCC)following HCV eradication remains an unmet need.We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development.AIM To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy.METHODS One hundred treatment-naïve HCV patients with advanced fibrosis(F3/4)treated with direct-acting antivirals(DAAs)or peginterferon/ribavirin who achieved sustained virologic response[SVR,defined as undetectable HCV RNA throughout 12 wk(SVR12)for the DAA group or 24 wk(SVR24)for the interferon group after completion of antiviral therapy]were enrolled since 2003.The primary endpoint was the development of new-onset HCC.Standard HCC surveillance(abdominal ultrasound andα-fetoprotein)was performed every six months during the followup.Overall,64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment.RESULTS HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication.In univariate analysis,the Fibrosis-4 index(FIB-4),hemoglobin A1c(HbA1c),the dynamics of tumor necrosis factor-α(TNF-α),and TNF-like weak inducer of apoptosis(TWEAK)after antiviral therapy were significant HCC predictors.The multivariate Cox regression model showed thatΔTNF-α(≤-5.7 pg/mL)was the most important risk factor for HCC(HR=11.54,95%CI:2.27-58.72,P=0.003 in overall cases;HR=9.98,95%CI:1.88-52.87,P=0.007 in the interferon group).An HCC predictive model comprising FIB-4,HbA1c,ΔTNF-α,andΔTWEAK had excellent performance,with 3-,5-,10-,and 13-year areas under the curve of 0.882,0.864,0.903,and 1.000,respectively.The 5-year accumulative risks of HCC were 0%,16.9%,and 40.0%in the low-,intermediate-,and high-risk groups,respectively.CONCLUSION Downregulation of serum TNF-αsignificantly increases the risk of HCC after HCV eradication.A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.展开更多
AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.
Objective: To synthesis silver nanoparticles(Ag NPs) by using extract of saffron(Crocus sativus L.) wastages and to test their antibacterial activity against six bacteria.Methods: In this paper, the synthesis of Ag NP...Objective: To synthesis silver nanoparticles(Ag NPs) by using extract of saffron(Crocus sativus L.) wastages and to test their antibacterial activity against six bacteria.Methods: In this paper, the synthesis of Ag NPs using aqueous extract of saffron wastage as a green method without any chemical stabilizer and reducer is demonstrated. The synthesized Ag NPs were determined by UV–vis spectrum, high resolution transmission electron microscopy, X-ray diffraction, and Fourier transmission infrared spectroscopy analysis.Results: UV–vis spectrum showed a peak at 450 nm due to excitation of surface plasmon vibrations. Fourier transmission infrared spectroscopy showed that nanoparticles were capped with plant secondary metabolites. X-ray diffraction analysis also demonstrated that the size range of the synthesized nanoparticles was 12–20 nm. Transmission electron microscope image illustrated Ag NPs with spherical shape and an average size of15 nm. The result of antibacterial activities showed that the biosynthesized Ag NPs had an inhibiting activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Shigella flexneri and Bacillus subtilis.Conclusions: The biosynthesized Ag NPs showed significant antibacterial effect against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Shigella flexneri and Bacillus subtilis, so, it can be used in biomedical applications.展开更多
Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Teh...Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Tehran, Iran. Methods: In this cross-sectional descriptive study, 100 strains of A. baumannii isolated from burn patients visiting teaching hospitals of Tehran were collected from January 2016 to November 2017. After A. baumannii strains were confirmed, antimicrobial susceptibility testing was done via Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines. PCR amplification was performed for detection of β-lactamase adeR, OprD, adeS genes among A. baumannii strains. Results: All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime, ciprofloxacin, and piperacillin, and most isolates indicated high resistance (95%-97%) to meropenem, imipenem, gentamicin, ceftriaxone, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and tetracycline. The most effective antibiotic against A. baumannii isolates was colistin (97% sensitivity), followed by tigecycline. The frequency of OprD, adeS, and adeR genes were 98%, 91%, and 77%, respectively. Conclusions: This study shows that the majority of A. baumannii isolates are highly resistant to the antibiotics most commonly used in burn patients. Also, high distribution of OprD and adeRS genes may be responsible for the observed resistances among A. baumannii isolates that demonstrate the possible role of both efflux pumps in simultaneous of carbapenemase production during antibiotic resistance.展开更多
Atherogenic dyslipidemia is a major risk factor for cardiovascular disease in patients with DM and characterized with high level of lipoprotein （a） （Lp （a）） and low level of adiponectin. Adiponectin serves as a ...Atherogenic dyslipidemia is a major risk factor for cardiovascular disease in patients with DM and characterized with high level of lipoprotein （a） （Lp （a）） and low level of adiponectin. Adiponectin serves as a regulator in glucose and lipid metabolism therefore is essential for maintaining response to insulin. Lp （a） is a cholesterol rich compound, so agents with hypoglycemic properties are suitable for treatment of diabetes that could improve atherogenic dyslipidemia. The major goal of this study was to investigate antioxidant capacity of natural honey as well as levels of adiponectin, Lp （a） and AlP （atherogenic index of plasma） in honey treated experimental diabetes. Twenty eight streptozotocin-induced diabetic male wistar rats were randomized into four groups （seven animals each） and administered distilled water, natural honey 1 and 2g/kg and glibenclamide. After three weeks treatment, adiponectin, Lp （a）, MDA （malondialdehyde）, FBS （fasting blood sugar）, TG （triglyceride）, cholesterol, HDL-C （high density lipoprotein） and LDL-C （low density lipoprotein） were measured. AlP also was calculated. Data analysis showed that honey significantly reduced serum level of triglycerides （0.72 ± 0.02 mmol/L） and FBS （7.8 ±0.12 mmol/L） to normoglycemic levels in diabetic rats. Honey also significantly increased serum adiponectin （4.5 ± 0.26 rag/L） and HDL-C （0.72 ± 0.14 retool/L） levels in diabetic rats. Serum level ofLP （a） was declined in honey treated groups （25.5 ± 3.2 g/dL）. Also honey supplementation decreased MDA level and AIP to normoglycemic control group. Our study supports the hypothesis that honey has beneficial effects in diabetes by its anti-atherogenic effect. Increased adiponectin level in honey treated groups might be associated with better glycemic control and improved lipid profile. Accordingly agents that increase adiponectin levels might be valuable targets for decreasing the atherogenic risk in diabetes.展开更多
Since a lot of people get involved by COVID-19 infection and died and lots of them obliged to stay at home and teleworking due to its unknown contagious pneumonia in February and March 2020 in Iran and the world;and t...Since a lot of people get involved by COVID-19 infection and died and lots of them obliged to stay at home and teleworking due to its unknown contagious pneumonia in February and March 2020 in Iran and the world;and this number is growing,it seems necessary to study the diagnostic criteria of this virus,based on the recently published articles,and then compare them with Severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS).Corona viruses are the largest known RNA viruses able to infect humans and birds.These viruses can cause more serious respiratory diseases in elderly,or immunocompromised individuals.In this article,by comparing COVID-19,SARS and MERS viruses,we aim to find similarities and differences between these three which are from the same family and by expressing their diagnostic criteria,help care units to find patients faster and have enough time for treating them.展开更多
The aim of this study is to screen proteins interacting with interferon-α （IFN-α）. The IFN-α gene was amplified by polymerase chain reaction （PCR） and cloned into pGBKT-/vector, then the resulted pGBKT-/-IFN-α...The aim of this study is to screen proteins interacting with interferon-α （IFN-α）. The IFN-α gene was amplified by polymerase chain reaction （PCR） and cloned into pGBKT-/vector, then the resulted pGBKT-/-IFN-α vector was transformed into yeast strain AH109. The transformed yeast AH109 was mated with yeast Y187 containing liver cDNA library plasmid in 2 × YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium （SD/-Trp-Leu-His-Ade and SD/-Trp-Leu-His） con- taining X-α-gal for selection. After plasmid extraction and enzyme cutting analysis, the blue colonies were subjected to sequence analysis and the results were analyzed by bioinformatics. The results showed that IFN-α was successful cloned into the pGBKT7 vector. IFN-α was expressed and there was no selfactivation and toxicity in AH109. Thirty-four positive colonies were obtained after yeast-two hybrid technique screening. After sequence analysis, eight clones were found to have a binding effect with IFN-α protein. IFN-α was successfully cloned into the pGBKT7 vector. IFN-α protein was expressed and there was no self-activation and toxicity in AH109. Eight proteins that interacted with IFN-α, including vitronectin, fibrinogen A alpha polypeptide, HIV-1 Tat interactive protein 2, arginase, NADH dehydrogenase 1 beta subcomplex, transferrin receptor 2 alpha （TFR2）, HCC-1, alcohol dehydrogenase IB （ADHIB） have been identified as IFN-α-binding proteins.展开更多
Hepatocellular carcinoma(HCC),especially hepatitis B virus(HBV)-related,remains a major cause of cancerrelated mortality worldwide.Unless there is early detection with curative treatment,the 5-year survival rate of ad...Hepatocellular carcinoma(HCC),especially hepatitis B virus(HBV)-related,remains a major cause of cancerrelated mortality worldwide.Unless there is early detection with curative treatment,the 5-year survival rate of advanced HCC is less than 15%.The preventive strategies for HBV-related HCC are thus urgently needed to reduce the global burden of this disastrous cancer.Primary prevention involves the avoidance of viral infection through hepatitis B vaccination and interruption of viral transmission from patients with chronic HBV infection.Universal neonatal hepatitis B vaccination program has successfully reduced the prevalence of HBV carriage rate as well as HCC incidence in vaccinated cohorts.However,HBV elimination is still difficult to achieve.Regarding secondary prevention,long-term treatment with nucleos(t)ide analogues has been proven to reduce the risk of HBV-related HCC.Individual risk stratification and a periodic HCC surveillance in these patients could facilitate early HCC diagnosis.Finally,tertiary prevention can also be achieved by life-long treatment with NAs to reduce the risk of HCC recurrence after curative treatment of primary HCC.Challenges ahead include the fact that HBV is not yet curable by current antiviral agents.Combination therapy with direct anti-HBV agents and host-targeting immunomodulatory agents is under active development.In addition,HCC risk cannot be eliminated even in patients with HBsAg seroclearance or functional cure.Therefore,HCC surveillance is strongly recommended for every patient with chronic HBV infection.展开更多
Hepatocellular carcinoma(HCC)oncogenesis in the absence of alcoholic liver disease and chronic viral hepatitis has aroused growing clinical concern in clinical practice.
Background and Aims:Early detection of hepatocellular carcinoma(HCC)is crucial for improving survival in patients with chronic hepatitis.The GALAD algorithm combines gen-der(biological sex),age,α-fetoprotein(AFP),Len...Background and Aims:Early detection of hepatocellular carcinoma(HCC)is crucial for improving survival in patients with chronic hepatitis.The GALAD algorithm combines gen-der(biological sex),age,α-fetoprotein(AFP),Lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and protein in-duced by vitamin K absence or antagonist-II(PIVKA-II)for HCC detection.Similarly,the GAAD algorithm incorporates gender(biological sex),age,AFP,and PIVKA-II.This study aimed to assess the clinical utility of AFP-L3 in the GALAD algorithm and its potential synergies with ultrasound.We compared the clinical performance of GALAD with GAAD;AFP;AFP-L3;and PIVKA-II,with or without ultrasound,in Taiwan residents adults.Methods:A total of 439 serum samples were analyzed using a Cobas®e 601 analyzer(healthy con-trols,n=200;chronic liver disease controls,n=177;HCC cases,n=62).Performance was assessed through receiver operating characteristic curve analyses to calculate the area under the curve.Results:The area under the curve for dif-ferentiating early-stage HCC from patients with chronic liver disease was optimal for PIVKA-II(84.9%),GAAD(79.8%),and GALAD(79.4%),with slightly improved performance for detecting all-stage HCC.Clinical performance was unaffected by disease stage or etiology.Sensitivity for early-stage HCC was highest for GAAD(57.6%)and GALAD(57.6%).Sen-sitivity for each strategy was further enhanced when com-bined with ultrasound,regardless of disease stage or etiology(P<0.01).Conclusions:These findings indicate that the role of AFP-L3 in the GALAD algorithm is minimal,supporting the use of GAAD for HCC detection.A combination of GAAD,GALAD,or PIVKA-II with ultrasound may improve diagnostic efficiency compared with recommended strategies.展开更多
Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HC...Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).展开更多
Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale.Hepatitis C virus(HCV)infection remains one of the major ri...Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale.Hepatitis C virus(HCV)infection remains one of the major risk factors for HCC development.HCC is a heterogeneous disease,and the development of HCC caused by HCV is intricate and involves various factors,including genetic susceptibility,viral factors,immune response due to chronic inflammation,alcohol abuse,and metabolic dysfunction associated with fatty liver disease.In this review,we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection.We also discuss the potential translational implications,including novel biomarkers and drugs for treatment.Methods:A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.Key Content and Findings:Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV.The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease,especially during the initial stages when genetic alterations are uncommon.The enduring“epigenetic memory”of gene expression is believed to be regulated by epigenetic mechanisms,indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment.Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.Conclusions:By facilitating a more profound understanding of these aspects,this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.展开更多
Circulating tumor cells(CTCs),originating from primary neoplastic tissues,infiltrate blood vessels,migrate through the bloodstream,and establish secondary tumor foci.The detection of CTCs holds significant promise for...Circulating tumor cells(CTCs),originating from primary neoplastic tissues,infiltrate blood vessels,migrate through the bloodstream,and establish secondary tumor foci.The detection of CTCs holds significant promise for early-stage identification,diagnostic precision,therapeutic monitoring,and prognostic evaluation.It offers a non-invasive approach and has broad clinical relevance in cancer management.This comprehensive review primarily focused on CTCs as biomarkers in the diagnostic,therapeutic,and prognostic surveillance of hepatocellular carcinoma,compared their correlation with key clinical parameters and the identification of gene characteristics.It also highlighted current methodologies in CTC detection.Despite approval by the U.S.Food and Drug Administration for select malignancies,the comprehensive integration of CTCs into routine clinical practice requires procedural standardization and a deeper understanding of the underlying molecular intricacies.The challenges in CTC detection,including limited quantity,technical impediments,and cellular heterogeneity,call for concerted and further investigational efforts to advance precision in cancer diagnostics and prognostication,thus realizing the objectives of precise and personalized medicine.展开更多
文摘AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METHODS： The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA （HBV DNA） level and hepatitis B e antigen （HBeAg） were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS： During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio： 95.74 （12.13-891.31）, P 〈 0.0001], male sex [odds ratio： 7.61 （2.20-47.95）; P = 0.006], and higher Iogzo HBV DNA [odds ratio： 4.69 （1.16-20.43）; P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio： 26.51 （2.36-381.47）; P = 0.007], presence of precore mutants [odds ratio： 4.23 （1.53-19.58）, P = 0.02] and presence of basal core promoter mutants [odds ratio： 2.93 （1.24-7.57）; P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION： Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.
基金Supported by Grants from the National Taiwan UniversityDe-partment of Health,Executive Yuan,TaiwanTaiwan Liver Disease Consortium(TLC),National Research Program for Bio-pharmaceuticals(NRPB),Taiwan,NSC100-2325-B-002-052
文摘Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.
基金Kaohsiung Medical University and Kaohsiung Medical University Hospital(KMU-KMUH Co-Project of Key Research),No.KMU-DK107004.
文摘BACKGROUND Chronic hepatitis C virus(HCV)infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood.Clearance of HCV by antivirals results in host immune modification,which may interfere with immune-mediated cancer surveillance.Identifying HCV patients who remain at risk of hepatocellular carcinoma(HCC)following HCV eradication remains an unmet need.We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development.AIM To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy.METHODS One hundred treatment-naïve HCV patients with advanced fibrosis(F3/4)treated with direct-acting antivirals(DAAs)or peginterferon/ribavirin who achieved sustained virologic response[SVR,defined as undetectable HCV RNA throughout 12 wk(SVR12)for the DAA group or 24 wk(SVR24)for the interferon group after completion of antiviral therapy]were enrolled since 2003.The primary endpoint was the development of new-onset HCC.Standard HCC surveillance(abdominal ultrasound andα-fetoprotein)was performed every six months during the followup.Overall,64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment.RESULTS HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication.In univariate analysis,the Fibrosis-4 index(FIB-4),hemoglobin A1c(HbA1c),the dynamics of tumor necrosis factor-α(TNF-α),and TNF-like weak inducer of apoptosis(TWEAK)after antiviral therapy were significant HCC predictors.The multivariate Cox regression model showed thatΔTNF-α(≤-5.7 pg/mL)was the most important risk factor for HCC(HR=11.54,95%CI:2.27-58.72,P=0.003 in overall cases;HR=9.98,95%CI:1.88-52.87,P=0.007 in the interferon group).An HCC predictive model comprising FIB-4,HbA1c,ΔTNF-α,andΔTWEAK had excellent performance,with 3-,5-,10-,and 13-year areas under the curve of 0.882,0.864,0.903,and 1.000,respectively.The 5-year accumulative risks of HCC were 0%,16.9%,and 40.0%in the low-,intermediate-,and high-risk groups,respectively.CONCLUSION Downregulation of serum TNF-αsignificantly increases the risk of HCC after HCV eradication.A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.
基金Supported by NIH Clinical Trial Registration,No.NCT00247728(this trial was cosponsored by Progen Industries Limited,Brisbane,Australia and Medigen Biotechnology Corporation,TaipeiTaiwan)to Chen PJ,Lai KL and Chang SSCTaiwan Liver Disease Consortium,the National Research Program for Biopharmaceuticals,and the National Science Council,Taiwan,NSC1002325-B-002-052NSC102-2325-B-002-079
文摘AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.
基金Supported by Department of Chemistry,University of Birjand(Grant No.4567:12/10/93)with cooperation of Birjand University of Medical Sciences
文摘Objective: To synthesis silver nanoparticles(Ag NPs) by using extract of saffron(Crocus sativus L.) wastages and to test their antibacterial activity against six bacteria.Methods: In this paper, the synthesis of Ag NPs using aqueous extract of saffron wastage as a green method without any chemical stabilizer and reducer is demonstrated. The synthesized Ag NPs were determined by UV–vis spectrum, high resolution transmission electron microscopy, X-ray diffraction, and Fourier transmission infrared spectroscopy analysis.Results: UV–vis spectrum showed a peak at 450 nm due to excitation of surface plasmon vibrations. Fourier transmission infrared spectroscopy showed that nanoparticles were capped with plant secondary metabolites. X-ray diffraction analysis also demonstrated that the size range of the synthesized nanoparticles was 12–20 nm. Transmission electron microscope image illustrated Ag NPs with spherical shape and an average size of15 nm. The result of antibacterial activities showed that the biosynthesized Ag NPs had an inhibiting activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Shigella flexneri and Bacillus subtilis.Conclusions: The biosynthesized Ag NPs showed significant antibacterial effect against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Shigella flexneri and Bacillus subtilis, so, it can be used in biomedical applications.
文摘Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Tehran, Iran. Methods: In this cross-sectional descriptive study, 100 strains of A. baumannii isolated from burn patients visiting teaching hospitals of Tehran were collected from January 2016 to November 2017. After A. baumannii strains were confirmed, antimicrobial susceptibility testing was done via Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines. PCR amplification was performed for detection of β-lactamase adeR, OprD, adeS genes among A. baumannii strains. Results: All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime, ciprofloxacin, and piperacillin, and most isolates indicated high resistance (95%-97%) to meropenem, imipenem, gentamicin, ceftriaxone, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and tetracycline. The most effective antibiotic against A. baumannii isolates was colistin (97% sensitivity), followed by tigecycline. The frequency of OprD, adeS, and adeR genes were 98%, 91%, and 77%, respectively. Conclusions: This study shows that the majority of A. baumannii isolates are highly resistant to the antibiotics most commonly used in burn patients. Also, high distribution of OprD and adeRS genes may be responsible for the observed resistances among A. baumannii isolates that demonstrate the possible role of both efflux pumps in simultaneous of carbapenemase production during antibiotic resistance.
文摘Atherogenic dyslipidemia is a major risk factor for cardiovascular disease in patients with DM and characterized with high level of lipoprotein （a） （Lp （a）） and low level of adiponectin. Adiponectin serves as a regulator in glucose and lipid metabolism therefore is essential for maintaining response to insulin. Lp （a） is a cholesterol rich compound, so agents with hypoglycemic properties are suitable for treatment of diabetes that could improve atherogenic dyslipidemia. The major goal of this study was to investigate antioxidant capacity of natural honey as well as levels of adiponectin, Lp （a） and AlP （atherogenic index of plasma） in honey treated experimental diabetes. Twenty eight streptozotocin-induced diabetic male wistar rats were randomized into four groups （seven animals each） and administered distilled water, natural honey 1 and 2g/kg and glibenclamide. After three weeks treatment, adiponectin, Lp （a）, MDA （malondialdehyde）, FBS （fasting blood sugar）, TG （triglyceride）, cholesterol, HDL-C （high density lipoprotein） and LDL-C （low density lipoprotein） were measured. AlP also was calculated. Data analysis showed that honey significantly reduced serum level of triglycerides （0.72 ± 0.02 mmol/L） and FBS （7.8 ±0.12 mmol/L） to normoglycemic levels in diabetic rats. Honey also significantly increased serum adiponectin （4.5 ± 0.26 rag/L） and HDL-C （0.72 ± 0.14 retool/L） levels in diabetic rats. Serum level ofLP （a） was declined in honey treated groups （25.5 ± 3.2 g/dL）. Also honey supplementation decreased MDA level and AIP to normoglycemic control group. Our study supports the hypothesis that honey has beneficial effects in diabetes by its anti-atherogenic effect. Increased adiponectin level in honey treated groups might be associated with better glycemic control and improved lipid profile. Accordingly agents that increase adiponectin levels might be valuable targets for decreasing the atherogenic risk in diabetes.
文摘Since a lot of people get involved by COVID-19 infection and died and lots of them obliged to stay at home and teleworking due to its unknown contagious pneumonia in February and March 2020 in Iran and the world;and this number is growing,it seems necessary to study the diagnostic criteria of this virus,based on the recently published articles,and then compare them with Severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS).Corona viruses are the largest known RNA viruses able to infect humans and birds.These viruses can cause more serious respiratory diseases in elderly,or immunocompromised individuals.In this article,by comparing COVID-19,SARS and MERS viruses,we aim to find similarities and differences between these three which are from the same family and by expressing their diagnostic criteria,help care units to find patients faster and have enough time for treating them.
文摘The aim of this study is to screen proteins interacting with interferon-α （IFN-α）. The IFN-α gene was amplified by polymerase chain reaction （PCR） and cloned into pGBKT-/vector, then the resulted pGBKT-/-IFN-α vector was transformed into yeast strain AH109. The transformed yeast AH109 was mated with yeast Y187 containing liver cDNA library plasmid in 2 × YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium （SD/-Trp-Leu-His-Ade and SD/-Trp-Leu-His） con- taining X-α-gal for selection. After plasmid extraction and enzyme cutting analysis, the blue colonies were subjected to sequence analysis and the results were analyzed by bioinformatics. The results showed that IFN-α was successful cloned into the pGBKT7 vector. IFN-α was expressed and there was no selfactivation and toxicity in AH109. Thirty-four positive colonies were obtained after yeast-two hybrid technique screening. After sequence analysis, eight clones were found to have a binding effect with IFN-α protein. IFN-α was successfully cloned into the pGBKT7 vector. IFN-α protein was expressed and there was no self-activation and toxicity in AH109. Eight proteins that interacted with IFN-α, including vitronectin, fibrinogen A alpha polypeptide, HIV-1 Tat interactive protein 2, arginase, NADH dehydrogenase 1 beta subcomplex, transferrin receptor 2 alpha （TFR2）, HCC-1, alcohol dehydrogenase IB （ADHIB） have been identified as IFN-α-binding proteins.
基金supported by grants from the National Taiwan University Hospital,the Ministry of Health and Welfare,and the Ministry of Science and Technology,Executive Yuan,Taiwan.
文摘Hepatocellular carcinoma(HCC),especially hepatitis B virus(HBV)-related,remains a major cause of cancerrelated mortality worldwide.Unless there is early detection with curative treatment,the 5-year survival rate of advanced HCC is less than 15%.The preventive strategies for HBV-related HCC are thus urgently needed to reduce the global burden of this disastrous cancer.Primary prevention involves the avoidance of viral infection through hepatitis B vaccination and interruption of viral transmission from patients with chronic HBV infection.Universal neonatal hepatitis B vaccination program has successfully reduced the prevalence of HBV carriage rate as well as HCC incidence in vaccinated cohorts.However,HBV elimination is still difficult to achieve.Regarding secondary prevention,long-term treatment with nucleos(t)ide analogues has been proven to reduce the risk of HBV-related HCC.Individual risk stratification and a periodic HCC surveillance in these patients could facilitate early HCC diagnosis.Finally,tertiary prevention can also be achieved by life-long treatment with NAs to reduce the risk of HCC recurrence after curative treatment of primary HCC.Challenges ahead include the fact that HBV is not yet curable by current antiviral agents.Combination therapy with direct anti-HBV agents and host-targeting immunomodulatory agents is under active development.In addition,HCC risk cannot be eliminated even in patients with HBsAg seroclearance or functional cure.Therefore,HCC surveillance is strongly recommended for every patient with chronic HBV infection.
文摘Hepatocellular carcinoma(HCC)oncogenesis in the absence of alcoholic liver disease and chronic viral hepatitis has aroused growing clinical concern in clinical practice.
基金funded by Roche Diagnostics GmbH and partly supported by the“Center of Excellence for Metabolic Associated Fatty Liver Disease,National Sun Yat-sen University,Kaohsiung”,under The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan.
文摘Background and Aims:Early detection of hepatocellular carcinoma(HCC)is crucial for improving survival in patients with chronic hepatitis.The GALAD algorithm combines gen-der(biological sex),age,α-fetoprotein(AFP),Lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and protein in-duced by vitamin K absence or antagonist-II(PIVKA-II)for HCC detection.Similarly,the GAAD algorithm incorporates gender(biological sex),age,AFP,and PIVKA-II.This study aimed to assess the clinical utility of AFP-L3 in the GALAD algorithm and its potential synergies with ultrasound.We compared the clinical performance of GALAD with GAAD;AFP;AFP-L3;and PIVKA-II,with or without ultrasound,in Taiwan residents adults.Methods:A total of 439 serum samples were analyzed using a Cobas®e 601 analyzer(healthy con-trols,n=200;chronic liver disease controls,n=177;HCC cases,n=62).Performance was assessed through receiver operating characteristic curve analyses to calculate the area under the curve.Results:The area under the curve for dif-ferentiating early-stage HCC from patients with chronic liver disease was optimal for PIVKA-II(84.9%),GAAD(79.8%),and GALAD(79.4%),with slightly improved performance for detecting all-stage HCC.Clinical performance was unaffected by disease stage or etiology.Sensitivity for early-stage HCC was highest for GAAD(57.6%)and GALAD(57.6%).Sen-sitivity for each strategy was further enhanced when com-bined with ultrasound,regardless of disease stage or etiology(P<0.01).Conclusions:These findings indicate that the role of AFP-L3 in the GALAD algorithm is minimal,supporting the use of GAAD for HCC detection.A combination of GAAD,GALAD,or PIVKA-II with ultrasound may improve diagnostic efficiency compared with recommended strategies.
基金partially supported by an investigator-initiated research grant(IN-US-334-4309)from Gilead Sciences to Stanford University.
文摘Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).
基金National Health and Medical Research Council of Australia(NHMRC)Program and Investigator Grants(2008983,1053206,and 1149976,to M.E.)Project and Ideas Grants(1107178 and 1108422,2001692,to M.E.).
文摘Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale.Hepatitis C virus(HCV)infection remains one of the major risk factors for HCC development.HCC is a heterogeneous disease,and the development of HCC caused by HCV is intricate and involves various factors,including genetic susceptibility,viral factors,immune response due to chronic inflammation,alcohol abuse,and metabolic dysfunction associated with fatty liver disease.In this review,we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection.We also discuss the potential translational implications,including novel biomarkers and drugs for treatment.Methods:A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.Key Content and Findings:Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV.The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease,especially during the initial stages when genetic alterations are uncommon.The enduring“epigenetic memory”of gene expression is believed to be regulated by epigenetic mechanisms,indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment.Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.Conclusions:By facilitating a more profound understanding of these aspects,this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.
基金supported in part by grants from the Ministry of Science and Technology,Taiwan(MOST 107-2314-B-037-082-MY3 to JFH,110-2314-B-03-073-MY3 to JFH)the National Science and Technology Council,Taiwan(NSTC112-2314-B-037-072 to YCL)+1 种基金the National Yang Ming Chiao Tung University-Kaohsiung Medical University Joint Research Project(NYCU-KMU-111-I001 to JFH,NYCU-KMU-112-I001 to JFH)and Kaohsiung Medical University Hospital(KMUH110-0R05 to JFH,KMUH110-0R20 to YCL,KMUH111-1M16 to YCL,KMUH111-1M17 to CMH,KMUH111-1R06 to JFH,KMUH SH11208 to YCL,KMUH-DK(B)110001-3 to YCL,KMUH-DK109006-2 to YCL).
文摘Circulating tumor cells(CTCs),originating from primary neoplastic tissues,infiltrate blood vessels,migrate through the bloodstream,and establish secondary tumor foci.The detection of CTCs holds significant promise for early-stage identification,diagnostic precision,therapeutic monitoring,and prognostic evaluation.It offers a non-invasive approach and has broad clinical relevance in cancer management.This comprehensive review primarily focused on CTCs as biomarkers in the diagnostic,therapeutic,and prognostic surveillance of hepatocellular carcinoma,compared their correlation with key clinical parameters and the identification of gene characteristics.It also highlighted current methodologies in CTC detection.Despite approval by the U.S.Food and Drug Administration for select malignancies,the comprehensive integration of CTCs into routine clinical practice requires procedural standardization and a deeper understanding of the underlying molecular intricacies.The challenges in CTC detection,including limited quantity,technical impediments,and cellular heterogeneity,call for concerted and further investigational efforts to advance precision in cancer diagnostics and prognostication,thus realizing the objectives of precise and personalized medicine.
