Background: Surface antigen (HBsAg) is the mean marker of hepatitis B virus infection. During the course of the infection, some patients lose the HBsAg and only the presence of anti-HBc antibody indicates previous con...Background: Surface antigen (HBsAg) is the mean marker of hepatitis B virus infection. During the course of the infection, some patients lose the HBsAg and only the presence of anti-HBc antibody indicates previous contact with the virus. Among these patients, some have detectable viral load (occult infection) but most without viral replication. There is no guideline regarding these patients. The aim of this study was to assess hepatic fibrosis in patients with only the hepatitis B virus contact marker “total anti-HBc”. Patients and methods: it was a descriptive and analytical cross-sectional study, conducted in three private hospitals from January to August 2022. Were included HBsAg-negative and HBc-positive patients, consulting in Gastroenterology departments. Noninvasive methods (APRI, FIB-4 and FIBROSCAN) were used to evaluate liver stiffness because of their easy accessibility and low-cost. The hepatic fibrosis was considered significant when the score determined by APRI, FIB-4 and FIBROSCAN® tests was respectively greater than 1.5;2.67 and 8 kPa corresponding to fibrosis level 2 (F2). Results: A total of 63 HBsAg-negative/total HBcAg-positive patients were included. The mean age was 49.9 ± 13.4 years. The male/female sex ratio was 1.78. Of the 63 patients, 19 had significant liver fibrosis (30.1%) among which 9 patients had HCC. The FIB-4 score outperformed the APRI score in assessing liver fibrosis, with a sensitivity of 84.2%, a specificity of 100% and a negative predictive value of 93.6%. In univariate analysis, there was a significant association between the occurrence of significant liver fibrosis and age over 40 years, dyslipidaemia, obesity, alcohol consumption, smoking, herbal medicine, negative anti-HBs immunological status and detectable viral load. Conclusion: Our study revealed a high prevalence of significant to severe hepatic fibrosis in anti-HBc positive patients. In most of the cases, the fibrosis was severe. Progression to HCC has also been possible. There is no consensus on the follow-up strategy for those patients. However, screening for hepatic fibrosis using noninvasive methods should be recommended for patients aged over 40 years, alcohol or herbal medicine users, patients with metabolic syndrome or occult hepatitis B. In HBsAg-negative/anti-HBc-positive patients, liver stiffness should be evaluated and if it is greater than F2, HCC screening should be started.展开更多
Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes ...Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.展开更多
The study was designed to find the prevalence of ANA antibodies and anti-dsDNA antibodies in samples tested at AFIP Rawalpindi and their correlation with age and gender and to find positive and negative predictive val...The study was designed to find the prevalence of ANA antibodies and anti-dsDNA antibodies in samples tested at AFIP Rawalpindi and their correlation with age and gender and to find positive and negative predictive values of ANA antibodies.For this purpose,twelve thousand nine hundred sixty-seven(12,967)patients were analyzed for ANA with four hundred sixty-eight(468)healthy samples tested as control and four thousand seven hundred three(4,703)patients tested for ds-DNA antibodies.Retrospective data of all samples tested by indirect immunofluorescence(IF)for ANA antibodies and dsDNA antibodies was collected.To address positive and negative predictive values another control group(autoimmunity not suspected)of serum samples was taken from the healthy population.For the first group,age,gender,ANA antibodies and ds-DNA antibodies results(both tests performed by IIF)data was collected from a computer record cell;for the second control group,ANA antibodies were performed by IIF.12,967 and 4,703 samples(Group 1)were tested for ANA antibodies and dsDNA antibodies,respectively,during this period.1,119(9%)and 99(2%)were found positive for ANA antibodies and ds DNA antibodies.Among these positive samples,850(76%)and 73(74%)were females respectively.Gender predisposition towards autoimmunity(ANA)was found significant with a P value of(P=0.001).Relation of age was also found significant with anti-ANA antibodies with a P value of(P=0.001).This study shows a negative correlation between age(P=0.025)and gender(P=0.001)with anti-dsDNA which is also significant.High prevalence was found below the mean age of 38 years(SD±16.635)for ANA antibodies and the mean age of 35 years(SD±15.066)for ds-DNA antibodies.The age of ANA antibodies and dsDNA antibodies positive patients ranged from 1 year old to 98 years old and 2 years old to 95 years old respectively.In the second(autoimmunity-free)control group,a total of 468 samples were tested for ANA antibodies and 9(2%)were found positive.Positive predictive value(PPV)was 8.6%and negative predictive value(NPV)was 98%.ANA is a sensitive test for autoimmunity and it is significantly related to female gender and increasing age.The low prevalence of ANA antibodies among clinically suspected cases suggests that rationalization of test prescriptions is needed.Anti-ds-DNA is also a sensitive test for diagnosis of SLE and it is significantly related to female gender and increasing age.展开更多
BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of gr...BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.展开更多
Quorum sensing(Qs)inhibition has emerged as a promising target for directed drug design,providing an appealing strategy for developing antimicrobials,particularly against infections caused by drug-resistant pathogens....Quorum sensing(Qs)inhibition has emerged as a promising target for directed drug design,providing an appealing strategy for developing antimicrobials,particularly against infections caused by drug-resistant pathogens.In this study,we designed and synthesized a total of 33β-nitrostyrene derivatives using 1-nitro-2-phenylethane(NPe)as the lead compound,to target the facultative anaerobic bacterial pathogen Serratia marcescens.The QS-inhibitory effects of these compounds were evaluated using S.marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026.Among the 33 newβ-nitrostyrene derivatives,(E)-1-methyl-4-(2-nitrovinyl)benzene(m-NPe,compound 28)was proven to be a potent inhibitor that reduced biofilm formation of S.marcescens NJ01 by 79%.Scanning electron microscopy(SEM)and confocal laser scanning microscopy(CLSM)results revealed that treatment with m-NPe(50μg/ml)not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%.m-NPe(50μg/ml)decreased virulence factors in S.marcescens NJ01,reducing the activity of protease,prodigiosin,and extracellular polysaccharide(EPs)by 36%,72%,and 52%,respectively.In S.marcescens 4547,the activities of hemolysin and EPs were reduced by 28%and 40%,respectively,outperforming the positive control,vanillic acid(VAN).The study also found that the expression levels of QS-and biofilm-related genes(flhD,fimA,fimC,sodB,bsmB,pigA,pigC,and shlA)were downregulated by 1.21-to 2.32-fold.Molecular dynamics analysis showed that m-NPe could bind stably to SmaR,Rhll,RhiR,LasR,and CviR proteins in a 0.1 M sodium chloride solution.Importantly,a microscale thermophoresis(MST)test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor(QSl)against S.marcescens.Overall,this study highlights the efficacy of m-NPe in suppressing the virulence factors of S.marcescens,identifying it as a new potential Qsl and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.展开更多
文摘Background: Surface antigen (HBsAg) is the mean marker of hepatitis B virus infection. During the course of the infection, some patients lose the HBsAg and only the presence of anti-HBc antibody indicates previous contact with the virus. Among these patients, some have detectable viral load (occult infection) but most without viral replication. There is no guideline regarding these patients. The aim of this study was to assess hepatic fibrosis in patients with only the hepatitis B virus contact marker “total anti-HBc”. Patients and methods: it was a descriptive and analytical cross-sectional study, conducted in three private hospitals from January to August 2022. Were included HBsAg-negative and HBc-positive patients, consulting in Gastroenterology departments. Noninvasive methods (APRI, FIB-4 and FIBROSCAN) were used to evaluate liver stiffness because of their easy accessibility and low-cost. The hepatic fibrosis was considered significant when the score determined by APRI, FIB-4 and FIBROSCAN® tests was respectively greater than 1.5;2.67 and 8 kPa corresponding to fibrosis level 2 (F2). Results: A total of 63 HBsAg-negative/total HBcAg-positive patients were included. The mean age was 49.9 ± 13.4 years. The male/female sex ratio was 1.78. Of the 63 patients, 19 had significant liver fibrosis (30.1%) among which 9 patients had HCC. The FIB-4 score outperformed the APRI score in assessing liver fibrosis, with a sensitivity of 84.2%, a specificity of 100% and a negative predictive value of 93.6%. In univariate analysis, there was a significant association between the occurrence of significant liver fibrosis and age over 40 years, dyslipidaemia, obesity, alcohol consumption, smoking, herbal medicine, negative anti-HBs immunological status and detectable viral load. Conclusion: Our study revealed a high prevalence of significant to severe hepatic fibrosis in anti-HBc positive patients. In most of the cases, the fibrosis was severe. Progression to HCC has also been possible. There is no consensus on the follow-up strategy for those patients. However, screening for hepatic fibrosis using noninvasive methods should be recommended for patients aged over 40 years, alcohol or herbal medicine users, patients with metabolic syndrome or occult hepatitis B. In HBsAg-negative/anti-HBc-positive patients, liver stiffness should be evaluated and if it is greater than F2, HCC screening should be started.
文摘Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.
文摘The study was designed to find the prevalence of ANA antibodies and anti-dsDNA antibodies in samples tested at AFIP Rawalpindi and their correlation with age and gender and to find positive and negative predictive values of ANA antibodies.For this purpose,twelve thousand nine hundred sixty-seven(12,967)patients were analyzed for ANA with four hundred sixty-eight(468)healthy samples tested as control and four thousand seven hundred three(4,703)patients tested for ds-DNA antibodies.Retrospective data of all samples tested by indirect immunofluorescence(IF)for ANA antibodies and dsDNA antibodies was collected.To address positive and negative predictive values another control group(autoimmunity not suspected)of serum samples was taken from the healthy population.For the first group,age,gender,ANA antibodies and ds-DNA antibodies results(both tests performed by IIF)data was collected from a computer record cell;for the second control group,ANA antibodies were performed by IIF.12,967 and 4,703 samples(Group 1)were tested for ANA antibodies and dsDNA antibodies,respectively,during this period.1,119(9%)and 99(2%)were found positive for ANA antibodies and ds DNA antibodies.Among these positive samples,850(76%)and 73(74%)were females respectively.Gender predisposition towards autoimmunity(ANA)was found significant with a P value of(P=0.001).Relation of age was also found significant with anti-ANA antibodies with a P value of(P=0.001).This study shows a negative correlation between age(P=0.025)and gender(P=0.001)with anti-dsDNA which is also significant.High prevalence was found below the mean age of 38 years(SD±16.635)for ANA antibodies and the mean age of 35 years(SD±15.066)for ds-DNA antibodies.The age of ANA antibodies and dsDNA antibodies positive patients ranged from 1 year old to 98 years old and 2 years old to 95 years old respectively.In the second(autoimmunity-free)control group,a total of 468 samples were tested for ANA antibodies and 9(2%)were found positive.Positive predictive value(PPV)was 8.6%and negative predictive value(NPV)was 98%.ANA is a sensitive test for autoimmunity and it is significantly related to female gender and increasing age.The low prevalence of ANA antibodies among clinically suspected cases suggests that rationalization of test prescriptions is needed.Anti-ds-DNA is also a sensitive test for diagnosis of SLE and it is significantly related to female gender and increasing age.
文摘BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.
基金This work was supported by the National Natural Science Foundation of China(Nos.82160664 and 31760246)the Hainan Province Science and Technology Special Fund(ZDYF2024SHFZ103)+1 种基金the Natural Science Foundation of Hainan Province(222RC557 and 221QN170)Anhui Laboratory of Molecule-Based Materials(fzj21006).
文摘Quorum sensing(Qs)inhibition has emerged as a promising target for directed drug design,providing an appealing strategy for developing antimicrobials,particularly against infections caused by drug-resistant pathogens.In this study,we designed and synthesized a total of 33β-nitrostyrene derivatives using 1-nitro-2-phenylethane(NPe)as the lead compound,to target the facultative anaerobic bacterial pathogen Serratia marcescens.The QS-inhibitory effects of these compounds were evaluated using S.marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026.Among the 33 newβ-nitrostyrene derivatives,(E)-1-methyl-4-(2-nitrovinyl)benzene(m-NPe,compound 28)was proven to be a potent inhibitor that reduced biofilm formation of S.marcescens NJ01 by 79%.Scanning electron microscopy(SEM)and confocal laser scanning microscopy(CLSM)results revealed that treatment with m-NPe(50μg/ml)not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%.m-NPe(50μg/ml)decreased virulence factors in S.marcescens NJ01,reducing the activity of protease,prodigiosin,and extracellular polysaccharide(EPs)by 36%,72%,and 52%,respectively.In S.marcescens 4547,the activities of hemolysin and EPs were reduced by 28%and 40%,respectively,outperforming the positive control,vanillic acid(VAN).The study also found that the expression levels of QS-and biofilm-related genes(flhD,fimA,fimC,sodB,bsmB,pigA,pigC,and shlA)were downregulated by 1.21-to 2.32-fold.Molecular dynamics analysis showed that m-NPe could bind stably to SmaR,Rhll,RhiR,LasR,and CviR proteins in a 0.1 M sodium chloride solution.Importantly,a microscale thermophoresis(MST)test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor(QSl)against S.marcescens.Overall,this study highlights the efficacy of m-NPe in suppressing the virulence factors of S.marcescens,identifying it as a new potential Qsl and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.
