BACKGROUND： Vitamin D is a fat-soluble sterol derivative that is predominantly synthesized in the liver and has multiple functions. The accumulative data showed that the clinical manifestations and prognosis of chron...BACKGROUND： Vitamin D is a fat-soluble sterol derivative that is predominantly synthesized in the liver and has multiple functions. The accumulative data showed that the clinical manifestations and prognosis of chronic liver diseases are associated with serum vitamin D levels. DATA SOURCES： A PubMed and Google Scholar search using terms： ＂vitamin D＂, ＂25 （OH）D＂, ＂liver disease＂, ＂viral hepatitis＂, ＂non-alcoholic fatty liver disease＂, ＂liver fibrosis＂, ＂cirrhosis＂, ＂hepatocellular carcinoma＂ and ＂autoimmune liver disease＂ was performed, and relevant articles published in English between January 2000 and March 2014 were reviewed. Fulb text publications relevant to the field were selected and relevant articles from reference lists were also included. RESULTS： The insufficiency or deficiency of vitamin D is common in various kinds of chronic liver diseases including viral hepatitis B and C. Serum 25-hydroxyvitamin D and vitamin D receptors are possibly interrelated with the incidence, treatment and prognosis of diseases. Though the evidence of vitamin D supplementation in viral hepatitis and associated liver diseases is still limited, there is great potential to apply this adjuvant therapy to improve the treatments. CONCLUSIONS： Although the exact role and mechanisms of vitamin D have not been fully elucidated in chronic liver diseases, it is potentially beneficial in the treatment of chronic liver diseases. Further mechanistic studies are needed to validate its clinical application.展开更多
Objective: To compare one-year outcomes of women started on antiretroviral therapy (ART) during?pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods: A retrospective chart review was performed at ...Objective: To compare one-year outcomes of women started on antiretroviral therapy (ART) during?pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods: A retrospective chart review was performed at three sites in Malawi. Women were included in the “pre-Option B+” cohort if they started ART during pregnancy for a CD4 count 3?or WHO 3/4 condition and in the “Option B+” cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher’s exact and ANOVA F-tests. Results: A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus 0.5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. Conclusions: At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.展开更多
Treatment modalities for hepatocellular carcinoma(HCC)vary from surgical techniques and interventional radiologic strategies to systemic therapy.For the latter,the use of immune checkpoint inhibitors(ICIs)has gained p...Treatment modalities for hepatocellular carcinoma(HCC)vary from surgical techniques and interventional radiologic strategies to systemic therapy.For the latter,the use of immune checkpoint inhibitors(ICIs)has gained popularity due to successful trials showing increased survival.In patients who have undergone liver transplantation,recurrence of HCC poses a significant challenge.There is indeed considerable debate on the efficacy and safety of ICI use in liver transplant recipients due to competing immune interests in maintaining a healthy graft and combating the tumor.Recent reports and case series have highlighted a role for the type of immune therapy,timing of therapy,tissue expression of PD-1 and modulation of immunosuppression,in the understanding of the efficacy and risks of ICIs for HCC in liver transplant.In this article,we appraise the available literature on the usage of ICIs for HCC in liver transplant recipients and provide perspectives on immune concerns as well as potential recommendations to consider during the management of such complex cases.展开更多
Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initi...Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.展开更多
Increased systemic microbial translocation contributes to the pathogenesis of various diseases.The magnitude of microbial translocation is measured by total bacterial 16S ribosomal DNA(rDNA)in plasma using quantitativ...Increased systemic microbial translocation contributes to the pathogenesis of various diseases.The magnitude of microbial translocation is measured by total bacterial 16S ribosomal DNA(rDNA)in plasma using quantitative PCR(qPCR).An evaluation of human systemic microbial translocation in vivo is crucial for revealing microbial product-mediated inflammation,innate immune activation and immune perturbation.The human gut harbors 1012 microorganisms per gram,and this is 10 times more than those from other sites.1,2 The intestinal mucosal barrier prevents pathogen invasion and nonpathogenic antigens residing within the intestinal lumen.1,2 Notably,the gut mucosal barrier prevents the host from being injured by pathogens,yet allows a very low level of bacterial product translocation to the system to maintain systemic immune homeostasis,as demonstrated by immune deficiencies in mice raised in sterile conditions.展开更多
基金supported by grants from the National Twelve-Five Project of China (2012ZX10002007-001-003)the Chinese Foundation for Hepatitis PreventionControl-TianQing Liver Disease Research Fund (cfhpc20132047)
文摘BACKGROUND： Vitamin D is a fat-soluble sterol derivative that is predominantly synthesized in the liver and has multiple functions. The accumulative data showed that the clinical manifestations and prognosis of chronic liver diseases are associated with serum vitamin D levels. DATA SOURCES： A PubMed and Google Scholar search using terms： ＂vitamin D＂, ＂25 （OH）D＂, ＂liver disease＂, ＂viral hepatitis＂, ＂non-alcoholic fatty liver disease＂, ＂liver fibrosis＂, ＂cirrhosis＂, ＂hepatocellular carcinoma＂ and ＂autoimmune liver disease＂ was performed, and relevant articles published in English between January 2000 and March 2014 were reviewed. Fulb text publications relevant to the field were selected and relevant articles from reference lists were also included. RESULTS： The insufficiency or deficiency of vitamin D is common in various kinds of chronic liver diseases including viral hepatitis B and C. Serum 25-hydroxyvitamin D and vitamin D receptors are possibly interrelated with the incidence, treatment and prognosis of diseases. Though the evidence of vitamin D supplementation in viral hepatitis and associated liver diseases is still limited, there is great potential to apply this adjuvant therapy to improve the treatments. CONCLUSIONS： Although the exact role and mechanisms of vitamin D have not been fully elucidated in chronic liver diseases, it is potentially beneficial in the treatment of chronic liver diseases. Further mechanistic studies are needed to validate its clinical application.
文摘Objective: To compare one-year outcomes of women started on antiretroviral therapy (ART) during?pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods: A retrospective chart review was performed at three sites in Malawi. Women were included in the “pre-Option B+” cohort if they started ART during pregnancy for a CD4 count 3?or WHO 3/4 condition and in the “Option B+” cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher’s exact and ANOVA F-tests. Results: A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus 0.5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. Conclusions: At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.
基金Robert Wood Johnson FoundationAFMDP+2 种基金University of Minnesota AIRPEU Horizon2020 program,project number 825510all to JDD。
文摘Treatment modalities for hepatocellular carcinoma(HCC)vary from surgical techniques and interventional radiologic strategies to systemic therapy.For the latter,the use of immune checkpoint inhibitors(ICIs)has gained popularity due to successful trials showing increased survival.In patients who have undergone liver transplantation,recurrence of HCC poses a significant challenge.There is indeed considerable debate on the efficacy and safety of ICI use in liver transplant recipients due to competing immune interests in maintaining a healthy graft and combating the tumor.Recent reports and case series have highlighted a role for the type of immune therapy,timing of therapy,tissue expression of PD-1 and modulation of immunosuppression,in the understanding of the efficacy and risks of ICIs for HCC in liver transplant.In this article,we appraise the available literature on the usage of ICIs for HCC in liver transplant recipients and provide perspectives on immune concerns as well as potential recommendations to consider during the management of such complex cases.
文摘Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.
基金supported by the National Institutes of Health Grants AI091526 and AI128864the Medical Research Service at the Ralph H.Johnson VA Medical Center Merit grant VA CSRD MERIT(CX001211).
文摘Increased systemic microbial translocation contributes to the pathogenesis of various diseases.The magnitude of microbial translocation is measured by total bacterial 16S ribosomal DNA(rDNA)in plasma using quantitative PCR(qPCR).An evaluation of human systemic microbial translocation in vivo is crucial for revealing microbial product-mediated inflammation,innate immune activation and immune perturbation.The human gut harbors 1012 microorganisms per gram,and this is 10 times more than those from other sites.1,2 The intestinal mucosal barrier prevents pathogen invasion and nonpathogenic antigens residing within the intestinal lumen.1,2 Notably,the gut mucosal barrier prevents the host from being injured by pathogens,yet allows a very low level of bacterial product translocation to the system to maintain systemic immune homeostasis,as demonstrated by immune deficiencies in mice raised in sterile conditions.
