Background Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the fourth most common cause of cancer-related mortality worldwide.Despite advances in immunotherapies and targeted treatments fo...Background Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the fourth most common cause of cancer-related mortality worldwide.Despite advances in immunotherapies and targeted treatments for HCC,chemotherapy remains a valuable first-line treatment.However,the efficacy of immunotherapy compared to that of chemotherapy is unknown.This study aimed to provide a comprehensive understanding of the effects of chemotherapy and immunotherapy on survival outcomes,response rates,and adverse effects.Methods A thorough literature search of multiple electronic databases,including MEDLINE(PubMed),Embase,Web of Science,Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov was conducted from each database’s inception to February 2024 to identify randomized controlled trials(RCTs)that compared first-line chemotherapy(doxorubicin,cisplatin,sorafenib,and fluorouracil)with immunotherapy(pembrolizumab nivolumab,and tislelizumab)for advanced HCC.Two reviewers independently identified the studies,obtained relevant information,and assessed the possibility of bias.The hazard ratios(HR)for progression-free survival(PFS)and overall survival(OS)were merged using random effects meta-analysis.Results Twenty studies with 1183 patients were examined.All studies had a high risk of bias.According to a meta-analysis,immunotherapy was linked to a significantly better PFS than chemotherapy(HR,1.44,95%confidence interval[CI],1.04-2.00,I2=32%).OS showed a similar trend,although the difference was not statistically significant(HR,1.26,95%CI,0.96-1.66,I2=0%).Sensitivity analysis revealed that immunotherapy continued to improve PFS compared to chemotherapy while having no discernible effect on OS.Conclusions First-line immunotherapy may offer PFS advantages over chemotherapy for the treatment of advanced HCC.However,a high risk of bias limits definitive conclusions.Larger,higher-quality RCTs are needed to confirm the potential benefits of OS and minimize bias.Although chemotherapy remains a valuable option in resource-limited settings where access to targeted therapies is restricted,the widespread availability of immunotherapy makes it essential to compare both treatments to determine the most appropriate first-line option for advanced HCC.展开更多
Objective:To evaluate the effect of methanolic extract and ethyl acetate fraction of methanol extract prepared from the seeds of Blepharis(B.)persica on testosterone biosynthesis and also to elucidate the underlying m...Objective:To evaluate the effect of methanolic extract and ethyl acetate fraction of methanol extract prepared from the seeds of Blepharis(B.)persica on testosterone biosynthesis and also to elucidate the underlying mechanism.Methods:Forty-eight male Wistar rats were divided into eight groups(n=6 per group).GroupⅠreceived 0.3%w/w gum acacia suspension p.o.and served as the normal control group.GroupⅡwas administered testosterone propionate in arachis oil i.m.as the positive control group.GroupⅢtoⅣreceived B.persica methanolic extract p.o.at doses of 50,100 and 200 mg/kg body weight.GroupⅥtoⅦreceived B.persica ethyl acetate fraction p.o.at doses of 50,100 and 200 mg/kg body weight.The testis was used for biochemical estimation and histological studies.The effects of methanolic extract and ethyl acetate fraction of B.persica on testicular testosterone,mRNA expression corresponding to steroidogenic acute regulatory protein(StAR)and 3β-hydroxysteroid dehydrogenase(3β-HSD)along with 3β-HSD enzyme assay were evaluated in testicular tissues and sperm concentration.Ethyl acetate fraction of B.persica was subjected to column chromatography.Invitro studies were performed using TM3 cell line at three dose levels(50,100,200μg/mL),each for methanolic extract,ethyl acetate fraction and 2-benzoxazolinone for evaluation of their comparative effect on testosterone production.Results:Ethyl acetate fraction and methanolic extract of B.persica could elevate the testicular testosterone content compared to the normal control group.The treatment with methanolic extract and ethyl acetate fraction of B.persica increased the expression of mRNA corresponding to StAR by 6.7 fold and 10.6 fold,respectively,whereas the mRNA expression of 3β-HSD increased by 5.7 fold and 7.3 fold,respectively.Moreover,fraction and extract treatment exhibited increased 3β-HSD activity in the testicular tissues and were found to elevate sperm concentration in seminal fluid.The spermatogenic potential was further ensured by histological observations.2-benzoxazolinone was isolated from ethyl acetate fraction and identified using spectral studies.It showed the ability to increase the testosterone content in the TM3 Leydig cells.Conclusions:Methanolic extract and ethyl acetate fraction of B.persica are able to increase the testicular testosterone in rats by elevating mRNA expression of StAR and 3β-HSD in testicular tissues,leading to increase the sperm concentration.展开更多
BACKGROUND Inflammatory bowel disease(IBD),with its rising prevalence rates is associated with an increased risk of cardiovascular and thromboembolic events.Antiplatelets and/or anticoagulants agents are often prescri...BACKGROUND Inflammatory bowel disease(IBD),with its rising prevalence rates is associated with an increased risk of cardiovascular and thromboembolic events.Antiplatelets and/or anticoagulants agents are often prescribed but the literature on the impact of long-term anticoagulation and/or antiplatelet use among patients hospitalized with IBD is scarce.The aim of this study is to assess the outcomes of patients hospitalized with IBD on antiplatelet and/or anticoagulant agents.AIM To investigate the effects of long-term use of antiplatelets/anticoagulants on clinical outcomes in patients hospitalized with IBD.METHODS We conducted a retrospective cohort study using the Nationwide Inpatient Sample database,including all adult IBD patients hospitalized in the United States from 2016 to 2019.Patient cohorts were stratified based on antiplatelet/anticoagulant therapy status.Multivariate regression analysis was done to assess outcomes,adjusting for potential confounders.The primary outcome was mortality,whereas length of stay(LOS),total parenteral nutrition,acute kidney injury,sepsis,shock,gastrointestinal bleeding,need for colonoscopy/sigmoidoscopy,abdominal surgery and total hospitalization charges were secondary outcomes.RESULTS Among 374744 hospitalized IBD patients,antiplatelet or anticoagulant therapy alone was associated with significantly lower in-hospital mortality and reduced healthcare utilization,including shorter LOS and decreased hospitalization costs.Combined therapy was associated with a protective effect on mortality,but did not reach statistical significance.Notably,therapy did not exacerbate disease severity or complications,although higher odds of gastrointestinal bleeding were observed.CONCLUSION Our study highlights the potential benefits of long-term anticoagulation/antiplatelet therapy in hospitalized IBD patients,with improved mortality outcomes and healthcare utilization.While concerns regarding gastrointestinal bleeding exist,the overall safety profile suggests a role for these agents in mitigating thromboembolic risks without exacerbating disease severity.Further research is needed to look at optimal treatment strategies and addressing limitations to guide clinical decision-making in this population.展开更多
文摘Background Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the fourth most common cause of cancer-related mortality worldwide.Despite advances in immunotherapies and targeted treatments for HCC,chemotherapy remains a valuable first-line treatment.However,the efficacy of immunotherapy compared to that of chemotherapy is unknown.This study aimed to provide a comprehensive understanding of the effects of chemotherapy and immunotherapy on survival outcomes,response rates,and adverse effects.Methods A thorough literature search of multiple electronic databases,including MEDLINE(PubMed),Embase,Web of Science,Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov was conducted from each database’s inception to February 2024 to identify randomized controlled trials(RCTs)that compared first-line chemotherapy(doxorubicin,cisplatin,sorafenib,and fluorouracil)with immunotherapy(pembrolizumab nivolumab,and tislelizumab)for advanced HCC.Two reviewers independently identified the studies,obtained relevant information,and assessed the possibility of bias.The hazard ratios(HR)for progression-free survival(PFS)and overall survival(OS)were merged using random effects meta-analysis.Results Twenty studies with 1183 patients were examined.All studies had a high risk of bias.According to a meta-analysis,immunotherapy was linked to a significantly better PFS than chemotherapy(HR,1.44,95%confidence interval[CI],1.04-2.00,I2=32%).OS showed a similar trend,although the difference was not statistically significant(HR,1.26,95%CI,0.96-1.66,I2=0%).Sensitivity analysis revealed that immunotherapy continued to improve PFS compared to chemotherapy while having no discernible effect on OS.Conclusions First-line immunotherapy may offer PFS advantages over chemotherapy for the treatment of advanced HCC.However,a high risk of bias limits definitive conclusions.Larger,higher-quality RCTs are needed to confirm the potential benefits of OS and minimize bias.Although chemotherapy remains a valuable option in resource-limited settings where access to targeted therapies is restricted,the widespread availability of immunotherapy makes it essential to compare both treatments to determine the most appropriate first-line option for advanced HCC.
基金supported by Charotar University of Science and Technology through CHARUSAT Research Grant sanctioned to Dr.Manan Raval[CHARUSAT SEED RESEARCH GRANT/RPCP/MAR/12].
文摘Objective:To evaluate the effect of methanolic extract and ethyl acetate fraction of methanol extract prepared from the seeds of Blepharis(B.)persica on testosterone biosynthesis and also to elucidate the underlying mechanism.Methods:Forty-eight male Wistar rats were divided into eight groups(n=6 per group).GroupⅠreceived 0.3%w/w gum acacia suspension p.o.and served as the normal control group.GroupⅡwas administered testosterone propionate in arachis oil i.m.as the positive control group.GroupⅢtoⅣreceived B.persica methanolic extract p.o.at doses of 50,100 and 200 mg/kg body weight.GroupⅥtoⅦreceived B.persica ethyl acetate fraction p.o.at doses of 50,100 and 200 mg/kg body weight.The testis was used for biochemical estimation and histological studies.The effects of methanolic extract and ethyl acetate fraction of B.persica on testicular testosterone,mRNA expression corresponding to steroidogenic acute regulatory protein(StAR)and 3β-hydroxysteroid dehydrogenase(3β-HSD)along with 3β-HSD enzyme assay were evaluated in testicular tissues and sperm concentration.Ethyl acetate fraction of B.persica was subjected to column chromatography.Invitro studies were performed using TM3 cell line at three dose levels(50,100,200μg/mL),each for methanolic extract,ethyl acetate fraction and 2-benzoxazolinone for evaluation of their comparative effect on testosterone production.Results:Ethyl acetate fraction and methanolic extract of B.persica could elevate the testicular testosterone content compared to the normal control group.The treatment with methanolic extract and ethyl acetate fraction of B.persica increased the expression of mRNA corresponding to StAR by 6.7 fold and 10.6 fold,respectively,whereas the mRNA expression of 3β-HSD increased by 5.7 fold and 7.3 fold,respectively.Moreover,fraction and extract treatment exhibited increased 3β-HSD activity in the testicular tissues and were found to elevate sperm concentration in seminal fluid.The spermatogenic potential was further ensured by histological observations.2-benzoxazolinone was isolated from ethyl acetate fraction and identified using spectral studies.It showed the ability to increase the testosterone content in the TM3 Leydig cells.Conclusions:Methanolic extract and ethyl acetate fraction of B.persica are able to increase the testicular testosterone in rats by elevating mRNA expression of StAR and 3β-HSD in testicular tissues,leading to increase the sperm concentration.
文摘BACKGROUND Inflammatory bowel disease(IBD),with its rising prevalence rates is associated with an increased risk of cardiovascular and thromboembolic events.Antiplatelets and/or anticoagulants agents are often prescribed but the literature on the impact of long-term anticoagulation and/or antiplatelet use among patients hospitalized with IBD is scarce.The aim of this study is to assess the outcomes of patients hospitalized with IBD on antiplatelet and/or anticoagulant agents.AIM To investigate the effects of long-term use of antiplatelets/anticoagulants on clinical outcomes in patients hospitalized with IBD.METHODS We conducted a retrospective cohort study using the Nationwide Inpatient Sample database,including all adult IBD patients hospitalized in the United States from 2016 to 2019.Patient cohorts were stratified based on antiplatelet/anticoagulant therapy status.Multivariate regression analysis was done to assess outcomes,adjusting for potential confounders.The primary outcome was mortality,whereas length of stay(LOS),total parenteral nutrition,acute kidney injury,sepsis,shock,gastrointestinal bleeding,need for colonoscopy/sigmoidoscopy,abdominal surgery and total hospitalization charges were secondary outcomes.RESULTS Among 374744 hospitalized IBD patients,antiplatelet or anticoagulant therapy alone was associated with significantly lower in-hospital mortality and reduced healthcare utilization,including shorter LOS and decreased hospitalization costs.Combined therapy was associated with a protective effect on mortality,but did not reach statistical significance.Notably,therapy did not exacerbate disease severity or complications,although higher odds of gastrointestinal bleeding were observed.CONCLUSION Our study highlights the potential benefits of long-term anticoagulation/antiplatelet therapy in hospitalized IBD patients,with improved mortality outcomes and healthcare utilization.While concerns regarding gastrointestinal bleeding exist,the overall safety profile suggests a role for these agents in mitigating thromboembolic risks without exacerbating disease severity.Further research is needed to look at optimal treatment strategies and addressing limitations to guide clinical decision-making in this population.
