“Time flies over us,but leaves its shadow behind”(Nathaniel Hawthorne,1860,The Marble Faun).The shadow that separates the latest guidance on vascular liver disorders of the American Association for the Study of Live...“Time flies over us,but leaves its shadow behind”(Nathaniel Hawthorne,1860,The Marble Faun).The shadow that separates the latest guidance on vascular liver disorders of the American Association for the Study of Liver Diseases(AASLD)from its former counterpart is 12 years long(1,2).Along the course,several guidelines from different societies have been published on this topic(3-7).As acknowledged in the preamble,the lack of high-quality evidence in the field led the AASLD to commission a guidance from an expert panel based on formal review and analysis of the literature.It thus differs from other guidelines that perform systematic reviews with explicit methods of searching,selection,and rating the quality of evidence and,if appropriate,meta-analysis on certain clinical questions(2).展开更多
AIM： To study the presence of sustained low diffusing capacity （DLco） after liver transplantation （LT） in patients with hepatopulmonary syndrome （HPS）. METHODS： Six patients with mild-to-severe HPS and 24 with...AIM： To study the presence of sustained low diffusing capacity （DLco） after liver transplantation （LT） in patients with hepatopulmonary syndrome （HPS）. METHODS： Six patients with mild-to-severe HPS and 24 without HPS who underwent LT were prospectively followed before and after LT at mid-term （median, 15 mo）. HPS patients were also assessed at Iong-tem （median, 86 mo）. RESULTS： Before LT, HPS patients showed lower PaO2 （71 ± 8 mmHg）, higher AaPO2 （43 ± 10 mmHg） and lower DLco （54% ± 9% predicted）, due to a combination of moderate-to-severe ventilation-perfusion （VA/Q） imbalance, mild shunt and diffusion limitation, than non- HPS patients （94 ± 4 mmHg and 19 ± 3 mmHg, and 85% ± 3% predicted, respectively） （P 〈 0.05 each）. Seven non-HPS patients had also reduced DLco （70% ± 4% predicted）. At mid- and long-term after LT, compared to pre- LT, HPS patients normalized PaO2 （91 ± 3 mmHg and 87 ± 5 mmHg）, AaPO2 （14 ± 3 mmHg and 23 ± 5 mmHg） and all VA/Q descriptors （P 〈 0.05 each） without changes in DLco （53% ± 8% and 56% ± 7% predicted, respectively）. Post-LT DLco in non-HPS patients with pre- LT low DLco was unchanged （75% ± 6% predicted）. CONCLUSION： While complete VA/Q resolution in HPS indicates a reversible functional disturbance, sustained low DLco after LT also present in some non-HPS patients, points to persistence of sub-clinical liver-induced pulmonary vascular changes.展开更多
The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for...The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for data mining and detected the biological behavior of endothelial cells(ECs)under hypoxia conditions and high dose dexamethasone to reveal the mechanisms above.Six differential expression mi RNAs(DE-miRNAs)were filtered from Gene Expression Omnibus(GEO)database GSE60093 which contained ECs treated with high dose glucocorticoid and control samples.Enrichment and PPI network analyses of the DE-miRNAs target genes showed the most remarkable pathway was HIF-1 signaling pathway and high dose glucocorticoid as a negative regulator of cell differentiation,energy metabolism,migration and cytokines secretion.Glucocorticoids also reduced the activity of autocrine/paracrine via limiting ion channels and transmembrane transporter process.In cytological experiment,HUVECs were divided into four groups:hypoxia group(H),hypoxia+dexamethasone group(HD),dexamethasone group(D),the normal group(N).Cell activity detection and Live/Dead dyeing showed cell activity and the number of live cells in Group H was higher than the other three groups at 24 h after intervention,while cell activity,number and proportion of live cells in HD group were worst.Cytoskeleton staining showed HD group met cytoskeleton form disorders.The scratch assay showed cell migration ability of Group H was strongest while cell migration ability of the HD group was worst.MIF expression in HD group showed a trend of bimodal,the peak of VEGF-A secretion lagged behind the MIF’s.Expression of MIF and VEGF-A in the HD group were low.High dose dexamethasone suppressed the active response of ECs to hypoxia stimulation via directly inhibiting the expression of MIF and interdicting autocrine/paracrine mechanism.We infered that the treatment with high dose glucocorticoid would inhibit neo-angiogenesis under hypoxia followed by aggravating hypoxia/ischemia and osteonecrosis.展开更多
文摘“Time flies over us,but leaves its shadow behind”(Nathaniel Hawthorne,1860,The Marble Faun).The shadow that separates the latest guidance on vascular liver disorders of the American Association for the Study of Liver Diseases(AASLD)from its former counterpart is 12 years long(1,2).Along the course,several guidelines from different societies have been published on this topic(3-7).As acknowledged in the preamble,the lack of high-quality evidence in the field led the AASLD to commission a guidance from an expert panel based on formal review and analysis of the literature.It thus differs from other guidelines that perform systematic reviews with explicit methods of searching,selection,and rating the quality of evidence and,if appropriate,meta-analysis on certain clinical questions(2).
基金Supported by Red Respira-ISCIII-RTIC-03/11 and Generalitat de Catalunya, No. 2005SGR-00822
文摘AIM： To study the presence of sustained low diffusing capacity （DLco） after liver transplantation （LT） in patients with hepatopulmonary syndrome （HPS）. METHODS： Six patients with mild-to-severe HPS and 24 without HPS who underwent LT were prospectively followed before and after LT at mid-term （median, 15 mo）. HPS patients were also assessed at Iong-tem （median, 86 mo）. RESULTS： Before LT, HPS patients showed lower PaO2 （71 ± 8 mmHg）, higher AaPO2 （43 ± 10 mmHg） and lower DLco （54% ± 9% predicted）, due to a combination of moderate-to-severe ventilation-perfusion （VA/Q） imbalance, mild shunt and diffusion limitation, than non- HPS patients （94 ± 4 mmHg and 19 ± 3 mmHg, and 85% ± 3% predicted, respectively） （P 〈 0.05 each）. Seven non-HPS patients had also reduced DLco （70% ± 4% predicted）. At mid- and long-term after LT, compared to pre- LT, HPS patients normalized PaO2 （91 ± 3 mmHg and 87 ± 5 mmHg）, AaPO2 （14 ± 3 mmHg and 23 ± 5 mmHg） and all VA/Q descriptors （P 〈 0.05 each） without changes in DLco （53% ± 8% and 56% ± 7% predicted, respectively）. Post-LT DLco in non-HPS patients with pre- LT low DLco was unchanged （75% ± 6% predicted）. CONCLUSION： While complete VA/Q resolution in HPS indicates a reversible functional disturbance, sustained low DLco after LT also present in some non-HPS patients, points to persistence of sub-clinical liver-induced pulmonary vascular changes.
基金the National Natural Science Foundation of Chinagrant number:81301562 and 81572147。
文摘The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for data mining and detected the biological behavior of endothelial cells(ECs)under hypoxia conditions and high dose dexamethasone to reveal the mechanisms above.Six differential expression mi RNAs(DE-miRNAs)were filtered from Gene Expression Omnibus(GEO)database GSE60093 which contained ECs treated with high dose glucocorticoid and control samples.Enrichment and PPI network analyses of the DE-miRNAs target genes showed the most remarkable pathway was HIF-1 signaling pathway and high dose glucocorticoid as a negative regulator of cell differentiation,energy metabolism,migration and cytokines secretion.Glucocorticoids also reduced the activity of autocrine/paracrine via limiting ion channels and transmembrane transporter process.In cytological experiment,HUVECs were divided into four groups:hypoxia group(H),hypoxia+dexamethasone group(HD),dexamethasone group(D),the normal group(N).Cell activity detection and Live/Dead dyeing showed cell activity and the number of live cells in Group H was higher than the other three groups at 24 h after intervention,while cell activity,number and proportion of live cells in HD group were worst.Cytoskeleton staining showed HD group met cytoskeleton form disorders.The scratch assay showed cell migration ability of Group H was strongest while cell migration ability of the HD group was worst.MIF expression in HD group showed a trend of bimodal,the peak of VEGF-A secretion lagged behind the MIF’s.Expression of MIF and VEGF-A in the HD group were low.High dose dexamethasone suppressed the active response of ECs to hypoxia stimulation via directly inhibiting the expression of MIF and interdicting autocrine/paracrine mechanism.We infered that the treatment with high dose glucocorticoid would inhibit neo-angiogenesis under hypoxia followed by aggravating hypoxia/ischemia and osteonecrosis.
